1.Fibroblast Growth Factors in Parkinson’s Disease: Multi-target Neuroprotective Mechanisms Involving Neuroinflammation, Cellular Stress, and Ferroptosis
Hui WANG ; Zi-Gui ZHOU ; Teng-Teng HAN ; Chang-Zhi YANG ; Xue-Wen TIAN
Progress in Biochemistry and Biophysics 2026;53(4):855-874
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.
2.Compact Fundus Imaging System Using Shack-Hartmann Wavefront Sensing for High-speed Auto-focus
Zhe-Kai LIN ; Long CHEN ; Geng-Yong ZHENG ; Jin-Tian HUANG ; Jia-Xin DONG ; Shang-Pan YANG ; Wen-Zheng DING ; Ding-An HAN ; Xue-Hua WANG ; Ya-Guang ZENG
Progress in Biochemistry and Biophysics 2026;53(4):1076-1086
ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.
3.A Fitting Method for Photoacoustic Pump-probe Imaging Based on Phase Correction
Zhuo-Jun XIE ; Hong-Wen ZHONG ; Run-Xiang LIU ; Bo WANG ; Ping XUE ; Bin HE
Progress in Biochemistry and Biophysics 2025;52(2):525-532
ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.
4.Development of dynamic multi-time-point clinical prediction models for bronchopulmonary dysplasia in preterm infants with gestational age<32 weeks
Wen LI ; Xue-Fei ZHANG ; Xiao-Ri HE ; Tao WANG ; Jing-Tao HU ; Wen LI ; Qing-Yi DONG ; Xiao-Yun GONG ; Yong-Hui YANG ; Ping-Yang CHEN
Chinese Journal of Contemporary Pediatrics 2025;27(12):1464-1474
Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.
5.Outcome of endovascular aortic repair under digital subtraction angiography in the treatment of Stanford type B aortic dissection
Jian-qiang WU ; Zheng WANG ; Zhi WEN ; Ming-wu TIAN ; Jing LYU ; Chang-xue WU
Journal of Regional Anatomy and Operative Surgery 2025;34(1):28-32
Objective To investigate the outcome of endovascular aortic repair under digital subtraction angiography (DSA) in the treatment of Stanford type B aortic dissection (TBAD). Methods A total of 104 TBAD patients admitted to our hospital from October 2019 to October 2022 were selected,of which 52 patients treated with best medication treat (BMT) were included into the BMT group,and 52 patients who underwent endovascular aortic repair under DSA on the basis of BMT were included into the combination group. The acute physiological and chronic health evaluation Ⅱ (APACHE Ⅱ) score,serum inflammatory indicators,liver and kidney function indicators,and coagulation function indicators before and after treatment,and hospital stay were compared between the two groups. Results The APACHE Ⅱ score,liver and kidney function indicators and inflammatory factors after treatment in the combination group were lower than those before treatment and in the BMT group (P<0.05). The combination group had more significant changes of coagulation function indicators after treatment than those before treatment and in the BMT group (P<0.05). The hospital stay of the combination group was shorter than that of the BMT group (P<0.05). Conclusion Endovascular aortic repair under DSA for TBAD can reduce inflammatory response,improve liver and kidney functions and coagulation function,and shorten the hospital stay,which has a better therapeutic effect than conservative drug treatment.
6.A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations.
Xue FENG ; Zi-Ai ZHU ; Hong-Tao WANG ; Hui-Wen ZHOU ; Ji-Wei LIU ; Ya SHEN ; Yu-Xian ZHANG ; Zhi-Qi XIONG
Neuroscience Bulletin 2025;41(5):805-820
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 Cdkl5492stop 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
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Disease Models, Animal
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Mice
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Protein Serine-Threonine Kinases/deficiency*
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Mutation/genetics*
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Epileptic Syndromes/genetics*
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Humans
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Dendritic Spines/pathology*
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Spasms, Infantile/genetics*
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Male
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Seizures/genetics*
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Mice, Inbred C57BL
7.Evaluation of Multimodal MRI in the Outcome of Traumatic Brain Injury in Rats After Treatment
Yiming YUE ; Lingfei WANG ; Wen LI ; Wenjun XUE
Chinese Journal of Medical Imaging 2025;33(11):1196-1202
Purpose To investigate the evaluation value of multimodal MRI in the outcome of traumatic brain injury(TBI)in rats.Materials and Methods A total of 30 TBI rat models were established,randomly divided into an untreated TBI group and a TBI treated group(hyperbaric oxygen)with 15 rats each.The Sham group with 15 rats was used as a healthy control,and the brain injury status of the rats was evaluated at 1 d,3 d,7 d,14 d and 28 d of modeling.Multimodal MRI was performed in parallel,and coronary T2WI,diffusion weighted imaging,diffusion kurtosis imaging and diffusion tensor imaging sequences were routinely scanned.The correlation between rat neurological function scores and various sequence parameters were analyzed,as well as multimodal MRI and the outcome of brain injury after TBI treatment in rats.Results The neurological function score and average kurtosis of the TBI treatment group were lower than those of the TBI untreated group(P<0.05).The apparent diffusion coefficient and anisotropy score of the TBI treatment group were higher than those of the TBI untreated group(P<0.05).The diffusion weighted imaging parameter apparent diffusion coefficient value and diffusion tensor imaging parameter fraction anisotropy value were negatively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=-0.675,-0.611,P<0.05),while the diffusion kurtosis imaging parameter mean kurtosis value was positively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=0.623,P<0.05).Conclusion Multimodal MRI can effectively evaluate the brain injury status of TBI rats and provide valuable information for dynamic evaluation after hyperbaric oxygen therapy for TBI,with high evaluation value in treatment outcomes.
8.Clinical and genetic characteristics of 14 children with sodium taurocholate co-transporting polypeptide deficiency
Rui-Xue MA ; Wen-Hai LUO ; Yi-Lin DAI ; Gui-Xian LI ; Fei WANG ; Ou JIANG ; Yin-Hong ZHANG ; Yun-Fen TIAN
Chinese Journal of Contemporary Pediatrics 2025;27(12):1514-1519
Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.
9.Clinical application value of ultrasonic blood flow detection in predicting frozen-thawed embryo transfer outcomes
Yacong WANG ; Xue KE ; Ruihua XIE ; Xiaoxi YANG ; Wen LUO ; Fang WANG
Chinese Journal of Reproduction and Contraception 2025;45(6):607-611
Objective:To explore the clinical application value of ultrasound detection of endometrial blood flow perfusion in evaluating the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles.Methods:A case-control study of 226 patients underwent preimplantation genetic testing (PGT) in the Department of Reproductive Medicine of Chengdu Women's and Children's Central Hospital was conducted. Patients enrolled from December 2021 to August 2024 underwent three-dimensional ultrasound endometrial receptivity testing on the day before FET. According to the pregnancy outcomes, they were divided into clinical pregnancy group ( n=155) and non-pregnancy group ( n=71). The general characteristics and endometrial receptivity parameters were compared between the two groups. Binary logistic regression was used to analyze the factors affecting pregnancy. Results:There was no significant difference in age, proportion of primary infertility, anti-Müllerian hormone, and antral follicle count between the two groups (all P>0.05). The duration of infertility in the clinical pregnancy group [(2.79±2.45) years] was significantly lower than that in the non-pregnancy group [(3.44±1.68) years, P=0.046], the basal luteinizing hormone (LH) level in clinical pregnancy group [(4.37±3.02) U/L] was higher than that in the non-pregnancy group [(3.59±2.02) U/L, P=0.047]. On the day before embryo transfer, the single-plane endometrial blood flow branch in the pregnancy group (4.83±1.57) was more than that in the non-pregnancy group (3.44±1.51), the difference was statistically significant ( P=0.001). The clinical pregnancy group had significantly different endometrial morphology types A [5.2% (8/155)], B [25.8% (40/155)], and C [69.0% (107/155)] compared with the non-pregnancy group [16.9% (12/71), 33.8% (24/71), 49.3% (35/71), P=0.003], respectively, the number of peristalsis waves in the clinical pregnancy group [1(0, 2)] was less than that in the non-pregnancy group [1(0, 4), P=0.046]. There were no significant differences in endometrial thickness, peristaltic wave classification, endometrial volume, endometrial and subendometrial blood flow pulse index/resistance index between the two groups (all P>0.05). Binary logistic regression analysis showed that the endometrial blood flow branch, endometrial peristalsis and basal LH level were independent factors affecting the pregnancy outcome of patients underwent PGT during FET cycle ( OR=1.855, 95% CI: 1.478-2.327, P=0.001; OR=0.813, 95% CI: 0.667-0.990, P=0.040; OR=1.163, 95% CI: 1.000-1.351, P=0.049). Among them, the area under the receiver operating characteristic curve of endometrial blood flow branches for the prediction of PGT-FET pregnancy outcome was 0.725, P=0.001. Conclusion:Endometrial blood flow branch, which represents the intensity of blood perfusion, has a good clinical value in evaluating the pregnancy outcome during FET cycle.
10.Programmed Cell Death in Endometriosis and Traditional Chinese Medicine Intervention: A Review
Zuoliang ZHANG ; Wanrun WANG ; Wen LI ; Xue HAN ; Xiaohong CHEN ; Nan SU ; Huiling LIU ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):48-57
Endometriosis (EMT) is a common disease with frequent occurrence and difficult to be cured in modern clinical practice of obstetrics and gynaecology. It is characterized by progressively worsening dysmenorrhoea, pelvic mass, and infertility. The incidence of EMT is growing and increasingly younger patients are diagnosed with this disease, which poses a serious threat to the reproductive and psychological health of women of childbearing age and adolescent females. However, the pathogenesis of EMT is still not completely clear, and the disease has a long course. Therefore, developing new therapies is an urgent clinical problem to be solved. Great progress has been achieved in the treatment of EMT with traditional Chinese medicine (TCM), while the underlying mechanism remains in exploration. Programmed cell death (PCD) is a cell death mode mediated by a variety of bio-molecules with specific signaling cascades. The known PCD processes include apoptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis, which all play a pivotal role in the development of EMT. Researchers have made achievements in the treatment of EMT with TCM, which regulates PCD via multiple pathways, routes, targets, and mechanisms. However, the progress in the regulation of PCD in the treatment of EMT with TCM remains to be reviewed. This paper reviews the research progress in the treatment of EMT with TCM from five PCD processes (apoptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis), with the aim of providing a theoretical basis for the clinical prevention and treatment of EMT.

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