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.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective To investigate the causal relationship between immune cells and various molecular subtypes of breast cancer (BC) by using two-sample Mendelian randomization (MR). Methods This study employed a two-sample MR analysis, with 731 immune cell types from the GWAS catalog as the exposure factors and four BC molecular subtypes (HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−) from the BCAC Consortium as the outcome variables. For causal inference, inverse variance weighting (IVW) was employed as the primary analytical method, alongside multiple consistency validation approaches, including MR-Egger, weighted median, weighted mode, simple mode, and Bayesian weighted Mendelian randomization. Reverse MR and sensitivity analyses were employed to effectively evaluate and exclude potential biases and interference from reverse causality. Results Significant causal associations were identified for specific immune cell phenotypes across subtypes. In HR+ BC, the HER2+ subtype was associated with seven immunophenotypes (five protective and two risk increasing), whereas the HER2− subtype was associated with eight immunophenotypes (four protective and four risk increasing). In HR− BC, the HER2+ subtype was associated with five immunophenotypes (one protective and four risk increasing), and the HER2− subtype (triple-negative BC) was associated with seven immunophenotypes (six protective and one risk-increasing). CD28+CD45RA−CD8+ T cells and naive CD8+ T cells have a bidirectional causal relationship with HR+/HER2+ breast cancer, Whereas the expression of CD8 on CD39+CD8+ cells also has a bidirectional relationship with HR+/HER2− breast cancer. Furthermore, CD4−CD8− NKT cells exhibited opposing effect directions in HER2+ versus HER2− subtypes. Conclusion From a genetic perspective, this study confirms the existence of subtype-specific causal associations between immune cell phenotypes and distinct molecular subtypes of BC, revealing heterogeneity in immune regulation.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and abnormal accumulation of α‑synuclein. Its pathogenesis involves multiple interconnected processes, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation, and impaired protein homeostasis. Extracellular signal-regulated kinase 1/2 (ERK1/2), a major component of the mitogen-activated protein kinase signaling network, plays an important role in neuronal survival, synaptic plasticity, stress responses, and cell death. However, accumulating evidence indicates that ERK signaling in PD is not unidirectional, as both insufficient activity and sustained overactivation have been associated with neuronal dysfunction and disease progression. In this review, we systematically summarize the evidence for the pathological and protective roles of ERK signaling in PD. Insufficient ERK activity may impair neurotrophic support, synaptic plasticity, mitochondrial homeostasis, and neuronal adaptation to stress, thereby increasing the vulnerability of dopaminergic neurons. In contrast, persistent and excessive ERK activation may promote neuroinflammation, oxidative stress, mitochondrial dysfunction, apoptosis, autophagy-lysosomal impairment, and abnormal α-synuclein accumulation. Conversely, moderate and transient ERK activation induced by neurotrophic factors, bioactive compounds, or exercise may enhance neuronal survival, antioxidant defense, synaptic plasticity, and functional recovery. These apparently contradictory findings suggest that ERK activation itself cannot be simply classified as either neuroprotective or neurotoxic. Based on the available evidence, we propose the concept of an “ERK activity window” to explain the context-dependent effects of ERK signaling in PD. This hypothesis suggests that ERK activity needs to remain within an appropriate dynamic range to maintain neuronal homeostasis and adaptive responses. ERK activity below this range may weaken neurotrophic support and stress resistance, whereas prolonged and high-intensity activation may exceed the adaptive capacity of neurons and glial cells, thereby promoting inflammatory and degenerative processes. Importantly, this functional window should not be regarded as a fixed threshold. Its biological effects are likely determined by the intensity and duration of activation, cell type, subcellular localization, upstream stimuli, interaction with other signaling pathways, and disease stage. This framework may therefore help reconcile the apparently inconsistent findings among different PD models and experimental conditions. From a therapeutic perspective, these findings indicate that ERK should not necessarily be considered a target for simple activation or inhibition. Instead, restoring ERK signaling toward an appropriate functional state may represent a more rational strategy. Exercise is of particular interest because it can simultaneously influence neurotrophic signaling, oxidative stress, inflammation, synaptic plasticity, and ERK activity, potentially promoting adaptive remodeling of ERK signaling according to pathological conditions. Nevertheless, current evidence is predominantly derived from cellular and animal studies, and the dynamic, cell-specific, and spatial characteristics of ERK signaling remain insufficiently defined. Blood-brain barrier penetration, long-term safety, preservation of physiological ERK functions, and the lack of reliable biomarkers for monitoring brain ERK activity also limit clinical translation. Importantly, the “ERK activity window” remains a theoretical framework, and direct clinical evidence that ERK modulation can alter the progression of human PD is currently lacking. Future studies should therefore integrate longitudinal analysis, cell-specific and spatial approaches, and clinical biomarker validation to determine whether precise regulation of ERK signaling can provide a viable strategy for disease-modifying intervention in PD.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

AIM To study the chemical constituents from the sticks and leaves of Croton cascarilloides Raeusch.and their biological activities.METHODS The 95％ethanol extract from the sticks and leaves of C.cascarilloides was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.LPS-induced NO RAW264.7 cell model induced by LPS was used to evaluate its anti-inflammatory activity in vitro.GES-1 injury model induced by taurocholic acid was used to screen the gastric mucosal protection activity.RESULTS Fourteen compounds were isolated and identified as bullatantriol(1),(-)-boscialin(2),(+)-dehydrovomifoliol(3),3-(hydroxylacetyl)-indole(4),pinoresinol(5),3,7-dimethyl-octa-1,7-diene-3,6-ol(6),(+)-syringaresinol(7),curcasinlignan B(8),cleomiscosin C(9),cleomiscosinD(10),2,6-dimethyl-octa-1,7-dien-3,6-diol(11),vanillin(12),vanillic acid(13),methyl vanillate(14).Compound 4 had certain anti-inflammatory activity,with IC50 values of 73.62 μmol/L.The protective rates of 25 μmol/L compounds 1-4,6,9-12 and 14 on gastric mucosal epithelial cells were 30.07％,34.18％,23.91％,30.92％,17.51％,19.69％,31.76％,22.46％,30.56％and 14.49％,respectively.CONCLUSION Compounds 1-14 are isolated from this plant for the first time.Compound 4 shows anti-inflammatory activity,1-4,6,9-12 and 14 show different degrees of gastric mucosal epithelial cell protective activity.

AIM To observe the protective effects and mechanism of Shuli Jiangzhuo Formula on cardiac function in a rat model of uremic cardiomyopathy(UCM).METHODS The successful UCM models established by 5/6 nephrectomy were randomly allocated into the model group,the valsartan group(8.33 mg/kg),and the low-dose,medium-dose and high-dose Shuli Jiangzhuo Formula groups(7.19,14.38,28.76 g/kg),in contrast to those of the sham operation group,followed by 8 weeks respective drug administration.Upon the completion of the pharmacological intervention,the rats had the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),ejection fraction(EF)and fractional shortening(FS)measured by echocardiography;the whole heart mass index(HMI)and left ventricular mass index(LVMI)detected;the renal function(serum creatinine,blood urea nitrogen)and the hemoglobin concentration detected;the mitochondrial morphology analyzed by observation of cardiomyocyte ultrastructure using transmission electron microscopy;the DNA damage in cardiomyocytes detected by TUNEL staining;the serum levels of IL-1β,IL-18 and BNP detected by ELISA;and the myocardial mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β detected by RT-qPCR and Western blot.RESULTS Compared with the sham operated controls,the model group demonstrated significant elevation of serum creatinine and urea nitrogen(P＜0.01);decreased hemoglobin concentration(P＜0.01);disorganized myocardial collagen fiber architecture,and pronounced mitochondrial swelling with ultrastructural damage;decreased EF and FS(P＜0.05);increased LVEDD and LVESD(P＜0.01);increased HMI and LVMI(P＜0.01);increased levels of serum IL-1β,IL-18 and BNP(P＜0.01);increased cardiomyocyte pyroptosis(P＜0.01);and enhanced mRNA and protein expressions of NLRP3,Caspase-1 and IL-1 β(P＜0.01).Compared to model group controls,the high-dose Shuli Jiantuo Formula intervention exhibited decreased levels of serum creatinine and urea nitrogen(P＜0.01);increased hemoglobin concentration(P＜0.01);reduced DNA fragmentation,alleviated mitochondrial swelling and mitigated ultrastructural damage;reduced LVEDD and LVESD(P＜0.05,P＜0.01);decreased HMI and LVMI(P＜0.01);downregulated levels of serum IL-1β,IL-18 and BNP(P＜0.01);decreased cardiomyocyte pyroptosis(P＜0.01);and inhibited mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β(P＜0.05,P＜0.01).CONCLUSION Shuli Jiangzhuo Formula demonstrates dual cardiorenal protective effects in UCM rats through suppression of the left ventricular hypertrophy progression and inhibition of the adverse ventricular remodeling processess.The therapeutic efficacy primarily stems from targeted suppression of NLRP3/Caspase-1 signaling pathway activation and substantial attenuation of cardiomyocyte pyroptosis cascade.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

OBJECTIVE To explore the early detection of large vestibular aqueduct syndrome(LVAS)in children by applying several audiological indicators.METHODS Ninety-two children with hearing loss(aged 1-70 months)were enrolled and divided into an LVAS group(45 cases)and a control group(47 cases).Eleven audiological indicators were statistically analyzed:lateral of hearing loss,the degree of hearing loss,configuration of hearing loss;ABR air-conduction threshold;ABR air-bone gap;ASSR average threshold;ASSR thresholds at 0.5,1,2,and 4 kHz;and tympanogram type.Indicators showing significant two-group differences were used to construct a visualized multifactorial linear prediction model using the R language.RESULTS Nine indicators demonstrated statistically significant differences between groups(P<0.05):laterality,configuration of hearing loss,ABR air-conduction threshold,ASSR average threshold,ASSR thresholds at all frequencies(0.5,1,2,4 kHz),and tympanogram type.A prediction model was established.When the total model score ranged between 200 and 240 points,the predicted LVAS risk probability was 0.1 to 0.99.The consistency index(C-index)was 0.85,indicating good predictive ability of the model.CONCLUSION The identified nine audiological indicators are valuable for the early detection of LVAS in children.The developed model can estimate LVAS risk.After refinement,this model holds potential to support early clinical diagnosis and intervention.