Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation ofα‑synuclein. Although extensive progress has been made in elucidating its pathogenesis, current therapeutic approaches remain largely symptomatic, and effective disease-modifying treatments are still unavailable. Increasing evidence indicates that PD is driven by the interaction of multiple pathological processes, including neuroinflammation, iron homeostasis dysregulation and ferroptosis, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, oxidative stress, and impaired protein homeostasis, which together contribute to neuronal vulnerability and degeneration. Fibroblast growth factors (FGFs) comprise a family of 22 ligands that play important roles in neural development, stress responses, metabolic regulation, and the maintenance of nervous system homeostasis. Recent studies have shown that several FGF family members, such as FGF1, FGF2, FGF9, and FGF21, exert neuroprotective effects in cellular and animal models of PD. These effects include the regulation of inflammatory responses, oxidative stress, iron homeostasis, cellular stress adaptation, and neuronal survival. Compared with therapeutic strategies targeting a single pathogenic pathway, FGFs appear to influence multiple disease-related processes, suggesting their potential relevance to the complex pathophysiology of PD. Experimental evidence indicates that altered FGF signaling may contribute to dopaminergic neuron dysfunction through the coordinated regulation of several interconnected mechanisms. FGFs have been reported to modulate neuroinflammation by affecting the activation of microglia and astrocytes, thereby influencing the inflammatory environment in the central nervous system. In addition, FGFs are involved in the regulation of iron homeostasis and ferroptosis, partly through antioxidant signaling pathways associated with NRF2, SLC7A11, and GPX4. Moreover, FGFs can alleviate ER stress and mitochondrial dysfunction by activating intracellular signaling pathways such as PI3K/AKT, AMPK-PGC-1α, as well as SIRT1-dependent programs, which support cellular energy metabolism and redox balance. Recent advances in single-cell and spatial transcriptomic studies further suggest that FGF signaling is not limited to neuron-intrinsic mechanisms but also involves interactions among different glial cell types. Altered FGF ligand-receptor communication between astrocytes and oligodendrocytes has been observed in PD models and is associated with increased susceptibility of dopaminergic neurons to oxidative stress and ferroptosis. These findings indicate that the biological effects of FGFs are influenced by cell type and disease stage and may vary under different pathological conditions. In this review, we summarize recent progress in understanding the roles of FGF family members in PD, with a focus on their involvement in iron homeostasis dysregulation and ferroptosis, neuroinflammation, cellular stress responses, and neuronal protection and regeneration. By integrating current evidence, this review aims to provide a clearer understanding of how FGFs participate in PD pathogenesis and to offer a theoretical basis for future studies exploring their potential value in disease-modifying therapeutic strategies.

Objective The study aimed to elucidate the population composition and seasonal distribution characteristics of mosquitoes in Laoshan District, Qingdao City, providing a scientific basis for the prevention and control of mosquito-borne infectious diseases. Methods Mosquito surveillance was conducted in Laoshan District in Qingdao City using light traps from April to November 2020-2022. Dominant mosquito species were identified using the Berger-Parker dominance index(I)and mosquito density was compared using the Kruskal-Wallis H test. The seasonal distribution characteristics of adult mosquitoes were analyzed using concentration and circular distribution method. Spearman rank correlation analysis was used to study the relationship between mosquito populations and meteorological factors with mean monthly temperature, mean monthly relative humidity, and mean monthly rainfall. Results The mean mosquito density for the trapping period was 9.771 females/(trap·night)in 2020,9.771 in 2021, and 9.427 in 2022. There was no statistically significant difference in mosquito density between different years(H = 0.095, P = 0.954). In total, 2 781 adult female mosquitoes comprising five species from four genera were captured over three years. Culex pipiens(I = 0.654), Aedes albopictus(I = 0.202), and Aedes aegypti(I = 0.118)were identified as dominant species. Seasonal fluctuations in the adult mosquitoes were unimodal, and primarily concentrated from June to September. The peak period of adult mosquito varied between years with statistical significance. (F = 3.838, P ＜ 0.05). Mosquito density was highly correlated with mean monthly temperature, mean monthly relative humidity and mean monthly precipitation(P＜ 0.05). Conclusions Cx. pipiens pallens, Ae. albopictus, and Ar. inamoratus are the dominant mosquito species in the Laoshan District of Qingdao City. The activity of adult mosquitoes is seasonal, and primarily concentrated in summer and autumn, during which the risk of mosquito-borne diseases such as dengue fever is increased.

Core fucosylation, catalyzed exclusively by fucosyltransferase 8 (FUT8), is an evolutionarily conserved post-translational modification that has emerged as a central regulatory hub linking liver homeostasis, chronic disease progression, and malignant transformation. Liver diseases, particularly hepatocellular carcinoma, remain a leading global health burden characterized by late diagnosis, limited therapeutic options, and poor overall survival. While aberrant glycosylation is now recognized as a hallmark of cancer and inflammatory disorders, existing research on FUT8-mediated core fucosylation in liver diseases remains fragmented: the dynamic functional switch of FUT8 from a homeostatic regulator to a pathological driver across the full disease continuum has not been systematically delineated, and the integrated mechanisms by which core fucosylation modulates oncogenic signaling, metabolic reprogramming, and immune evasion remain poorly understood. This review synthesizes recent advances to establish a unified framework for understanding the dual role of core fucosylation in liver physiology and pathology, and evaluates its translational potential for precision medicine. At the molecular level, FUT8’s unique catalytic specificity makes core fucosylation an irreplaceable modification, as evidenced by the perinatal lethality and severe organ dysfunction in Fut8 knockout mice. In hepatocellular carcinoma, genomic amplification of guanosine 5'-diphosphate-fucose biosynthetic enzymes provides metabolic support for aberrant core fucosylation. FUT8 expression is tightly regulated by a multi-layered network: transcriptional activation via Wnt/β‑catenin and wild-type p53, epigenetic upregulation by lncRNAs, post-transcriptional repression by miR-122-5p and miR-34a, and virus-specific induction by hepatitis B virus/hepatitis C virus. Physiologically, core fucosylation maintains liver homeostasis through four core mechanisms: it acts as a molecular switch for epidermal growth factor receptor/hepatocyte growth factor receptor signaling to enable liver regeneration; directs polarized secretion of hepatocyte-derived glycoproteins into bile ducts; modulates cholesterol metabolism via the hepatocyte nuclear factor 1α-proprotein convertase subtilisin/kexin type 9-low density lipoprotein receptor axis; and regulates aging through insulin‑like growth factor 1 receptor signaling. Pathologically, core fucosylation exhibits context-dependent dual functions: in liver fibrosis, FUT8 upregulation in hepatic stellate cells forms a negative feedback loop that limits excessive fibrogenesis; in hepatocellular carcinoma, however, aberrant FUT8 overexpression drives cell-autonomous malignancy by constitutively activating epidermal growth factor/hepatocyte growth factor receptor, transforming growth factor‑β/Smad, and Wnt/β‑catenin pathways, while simultaneously establishing a multi-layered immune evasion network by stabilizing programmed cell death ligand 1 and cluster of differentiation 47, and impairing natural killer cell homeostasis via interleukin‑2 receptor β glycosylation. Clinically, stage-specific core fucosylation biomarkers enable non-invasive monitoring of liver disease progression: low molecular mass kringle-Fc fusion protein outperforms conventional markers for early fibrosis detection, while alpha-fetoprotein-L3 and novel glycopeptides (α‑2‑macroglobulin N‑linked glycosylation site 1424, lumican core fucosylated peptide) significantly improve early hepatocellular carcinoma diagnosis, especially in alpha-fetoprotein-negative patients. Next-generation detection technologies (chemoenzymatic labeling, site-specific mass spectrometry) overcome the specificity limitations of traditional lectin assays. Therapeutically, four promising strategies are emerging: small-molecule FUT8 inhibitors, afucosylated antibodies with enhanced antibody‑dependent cellular cytotoxicity, Fuc-modified targeted drug delivery systems, and core fucose-specific lectins for NASH treatment. The core challenge for clinical translation lies in FUT8’s inherent “double-edged sword” effect, as systemic inhibition disrupts its essential physiological functions beyond pathological roles. Long-term systemic FUT8 blockade not only impairs post-injury liver regeneration by abrogating epidermal growth factor/hepatocyte growth factor receptor signaling but also disrupts cholesterol homeostasis via the hepatocyte nuclear factor 1α-proprotein convertase subtilisin/kexin type 9-low density lipoprotein receptor axis, leading to dyslipidemia and altered bile secretion. Critically, it compromises immune surveillance by destabilizing interleukin‑2 receptor β on natural killer cells, reducing their cytotoxic activity against malignant and virally infected cells, and impairs IgG Fc-mediated effector functions, increasing susceptibility to infections. This fundamental trade-off between therapeutic efficacy and systemic toxicity necessitates a paradigm shift from non-specific global inhibition to precision modulation of pathological core fucosylation. By addressing these critical challenges, FUT8-mediated core fucosylation has the potential to transform liver disease management from late-stage intervention to early detection and precision therapy, ultimately improving patient outcomes and reducing the global burden of liver diseases.

Access to the clinical application of medical technology is one of the core institutional contents of medical quality management， involving medical quality assurance， the achievement of patient safety goals， and medical service satisfaction. Medical technology is only permitted for clinical use after its safety and effectiveness have been verified through clinical research， as well as evaluated and reviewed by the medical technology clinical application management committee and ethics committee of this medical and health institution. Based on the relevant laws， regulations， and ethical principles， combined with the experience of ethical review in the clinical application of medical technology from some medical and health institutions， a thematic discussion was held to formulate ethical review guidelines for the clinical application of medical technology for references. These guidelines elaborated on the management system for access to the clinical application of medical technology in medical and health institutions， the system of ethics committees and the requirements of review norms， technical plans and their review points， key points for the implementation of informed consent， technical teams and conditions， and other aspects.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic metabolic disease with an increasing incidence worldwide, that poses a significant risk to public health. In many current clinical practices for diabetes management, conventional Western treatments, including oral or injectable hypoglycemic agents, have serious side effects. Given that traditional Chinese medicine (TCM) is characterized by a multi-component, multi-target and multi-pathway approach, its combination with Western medicine could enhance efficacy and reduce adverse effects. Consequently, the use of TCM as a potential auxiliary or alternative treatment for the prevention and/or management of T2DM has emerged as a research hotspot. This article reviews existing reports on TCM in the treatment of T2DM and provides a detailed discussion of its applications. By integrating relevant clinical evidence, this review summarizes the clinical data on 23 TCM formulas and Chinese patent medicines, comprehensively describing their efficacy and potential pharmacological mechanisms in the treatment of T2DM. This includes an exploration of the impacts of TCM-based therapeutic interventions on T2DM-related microRNAs and their target genes. We hope this review not only offers new insights for future research directions but also enhances the understanding of the scientific value of TCM. Please cite this article as: Ni HX, Cao LH, Gong XX, Zang ZY, Chang H. Traditional Chinese medicine for treatment of type 2 diabetes mellitus: Clinical evidence and pharmacological mechanisms. J Integr Med. 2025; 23(6):605-622.
Humans ; Diabetes Mellitus, Type 2/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/pharmacology* ; Hypoglycemic Agents/pharmacology*

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*