Abstract:Objective: To analyze the relationship between type 2 diabetes mellitus(T2DM)complicated by hypertension(HTN)and cognitive decline in middle-aged and elderly individuals, as well as the associated influencing factors. Methods: Middle-aged and elderly subjects who were treated at Sir Run Run Hospital Affiliated to Nanjing Medical University from September 2020 to September 2022 were enrolled and divided into four groups: patients with T2DM complicated by HTN(T2DMH group), patients with T2DM alone(T2DM group), patients with HTN alone(HTN group), and healthy controls(HC group). Clinical data were collected from the four groups. Cognitive and functional indicators were assessed using the Montreal cognitive assessment(MoCA), auditory verbal learning test(AVLT), trail making test(TMT) and digit span test(DST). Cognitive performance was compared among the four groups, and multivariate regression analysis was conducted to explore the associated influencing factors. Results: A total of 369 patients were enrolled in this study. These patients were assigned to four groups: the T2DMH group(n=105), T2DM group(n=106), HTN group(n=89), and HC group(n=69). No statistically significant differences were observed in age and years of education among the four groups(P > 0.05), indicating good comparability. The T2DMH group had higher HOMA-β than the T2DM group(P < 0.05), but DI did not differ between the two groups(P > 0.05); both were significantly lower than those in the HTN and HC groups(all P < 0.05). In terms of cognitive functions, the T2DMH group had worse performance in memory cognitive dimensions than the T2DM and HTN groups, and all indicators of cognitive domains in this group were significantly lower than those in the HC group(all P < 0.05). Cognitive function was significantly correlated with years of education, histories of T2DM and HTN, islet function and other indicators(P < 0.05). Multiple linear regression showed that years of education were positively associated with cognitive function; T2DM and HTN histories were significantly correlated with cognition, and alcohol consumption history as well as partial renal function parameters had varying degrees of correlation with cognitive performance(all P < 0.05). Conclusion: Patients with T2DM combined with HTN suffer from more severe metabolic disorders, organ damage and impaired islet function, accompanied by significant multidimensional cognitive decline, which is more severe than that in patients with isolated T2DM or isolated HTN. Disease duration of T2DM and HTN is independently and significantly associated with cognitive decline in middle-aged and elderly individuals. Higher education, better renal and islet function showed protective associations with cognition,though causal relationships require further validation in prospective cohort studies.

Abstract:Objective: To investigate the correlation between the oxygen desaturation rate (ODR) associated with obstructive respiratory events and type 2 diabetes mellitus (T2DM) as well as its vascular complications in patients with obstructive sleep apnea (OSA). Methods: A total of 493 patients with OSA who underwent polysomnography (PSG) at the Affiliated Huai' an No.1 People's Hospital of Nanjing Medical University between June 2023 and December 2024 were retrospectively included. Patients were divided into two groups: the T2DM group(n=218) and the non-T2DM group(n=275). Based on the peripheral oxygen saturation(SpO₂) signal from PSG, event-level ODR (ΔSpO₂/Δt) associated with obstructive respiratory events was calculated; individual-level ODR was defined as the median across all night events. Participants were stratified into tertiles according to ODR (with the Low-ODR group as reference), and a multivariable logistic regression model was constructed to assess the associations of ODR and conventional PSG parameters with the risk of T2DM and diabetic vascular complications. Results: There were no significant differences in age, apnea-hypopnea index(AHI), or oxygen desaturation index (ODI) between the two groups. However, the ODR was significantly higher in the T2DM group than that in the non-T2DM group [0.50(0.35, 0.67)%/s vs. 0.38(0.29, 0.52)%/s, P < 0.001]. Multivariable logistic regression analysis showed that, High-ODR was significantly associated with T2DM(OR=2.96,95%CI: 1.73-5.09, P < 0.001) and diabetic vascular complications(OR=3.91,95%CI:1.04-14.66,P < 0.05). Stratified analysis by sex further revealed that the association between ODR and the risk of T2DM was statistically significant only in male patients; the OR for T2DM in the males of High-ODR group was 3.64 times of the males in Low-ODR group(OR=3.64,95%CI: 1.78-7.43, P < 0.001). Conclusion: ODR is significantly associated with T2DM and its vascular complications in patients with OSA, and this association exhibits gender-related differences.

Abstract:Objective: The C-peptide is a by-product of proinsulin cleavage with recently identified probable pleiotropic protective effects in type 1 diabetic peripheral neuropathy(DPN). Up to now, through its physiological mechanisms like activating nitric oxide synthase, Na⁺/K⁺-ATPase and inhibiting nuclear factor kappa-B pathway, C-peptide can not only improve nerve blood flow and alleviate axonal injury, but also have antioxidant and anti-apoptotic effects. Apart from the molecular mechanism level, animal experiments showed that C-peptide could significantly improve nerve conduction velocity, blood flow and structural abnormalities in diabetic rats. Clinical trials have also shown that C-peptide replacement therapy improves nerve conduction velocity and vibration sensation in patients, and the long-acting formulation Peg-C peptide has more promise. Therefore, C-peptide may have a potential protective effect and clinical application prospect in type 1 DPN. Although it has been proven that C-peptide has an effective role in improving neurological function, its mechanism in the treatment of neuropathic pain has not yet been specifically elucidated. Furthermore, its effect on neuropathic pain symptoms, optimal dosing regimen, and effect on intraepidermalnerve fiber density (IENFD) still need further study.

Abstract:Objective: To investigate the neuroprotective effects of nanovesicles (NVs) derived from the human neural stem cell line ReN cell and to explore the underlying molecular mechanisms in Parkinson's disease (PD). Methods: PD mouse models were established in C57BL/6 mice by intraperitoneal injection of 20 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were treated via tail vein injection with nanovesicles obtained from extruded ReN cells (ReN-NV) or RVG peptide-modified ReN-NV (RVG-ReN-NV). Motor function was evaluated by the rotarod test and the pole test, and immunofluorescence staining was performed to assess the expression of tyrosine hydroxylase (TH) and the microglial marker Iba1 in the substantia nigra, as well as TH expression in the striatum. Western blot analysis was used to determine TH protein levels in the striatum. In vitro, a PD cell model was established by treating human neuroblastoma SH-SY5Y cells with 1 mmol/L 1-methyl-4-phenylpyridinium ion(MPP⁺). Cell viability was assessed using the CCK-8 assay, cytotoxicity was evaluated by lactate dehydrogenase (LDH) release assay, and the protein expression levels of Bcl-2 and Bax were measured by Western blotting. Results: The behavioral results showed that MPTP-treated mice displayed a significantly reduced latency to fall during the pole test, accompanied by an increased total descent time, suggesting the establishment of Parkinsonian-like motor impairment. Immunofluorescence analysis showed that ReN-NV alleviated the loss of TH-positive neurons in the substantia nigra and striatum induced by MPTP and reduced Iba1 expression in the substantia nigra, with RVG-ReN-NV exhibiting a more pronounced protective effect. Western blot analysis demonstrated that ReN-NV upregulated TH protein expression in the striatum. In vitro experiments showed that ReN-NV increased the viability of MPP⁺-treated SH-SY5Y cells, reduced LDH release, upregulated the expression of the anti-apoptotic protein Bcl-2, and downregulated the expression of the pro-apoptotic protein Bax. Conclusion: ReN cell-derived nanovesicles exert significant neuroprotective effects in MPTP/MPP⁺-induced PD models. RVG modification further enhances their brain-targeting protective efficacy, and the underlying mechanism may be associated with let-7i-5p-mediated inhibition of apoptotic pathways.

Abstract:Objective: To construct peptidyl-prolyl cis-trans isomerase never in mitosis A-interacting 1 (Pin1) knockout C17.2 neural stem cell (NSC) lines using CRISPR/Cas9 technology, elucidate the impact of Pin1 deficiency on the proliferation capacity of embryonic NSCs, and explore the underlying molecular mechanisms based on transcriptome sequencing. Methods: Specific single guide RNAs (sgRNAs) targeting exon 2 of the mouse Pin1 gene were designed to construct the CRISPR/Cas9 targeting vectors. These vectors were transfected into C17.2 NSCs, followed by G418 selection to obtain Pin1 knockout single-cell colonies. The knockout efficiency and stemness maintenance (Nestin expression) were validated by immunofluorescence and Western blot analyses. Cell proliferation was evaluated using BrdU incorporation assays and Ki67 immunofluorescence staining. Differentially expressed genes (DEGs) were screened via RNA-Seq and subjected to pathway enrichment analysis. The expression of DEGs was further validated by quantitative real-time PCR (qRT-PCR) and Western blot. Finally, DAPT, a γ-secretase inhibitor, was employed to block the Notch signaling pathway to verify its role in Pin1-mediated cell proliferation. Results: Three C17.2 cell clones with biallelic Pin1 knockout were successfully generated. Compared to wild-type cells, Pin1 knockout cells maintained positive Nestin expression, but exhibited significantly increased BrdU incorporation and Ki67-positive rates (P < 0.05), indicating a state of hyperproliferation. RNA-Seq and subsequent validation experiments demonstrated that Pin1 deletion resulted in the significant activation of the Notch signaling pathway, characterized by the marked upregulation of the Notch1 protein and its downstream target gene Hes1 (P < 0.05). Treatment with DAPT not only effectively inhibited the hyperactivation of the Notch1 pathway in Pin1 knockout cells but also significantly reduced their proliferation rate. Conclusion: Pin1 functions as a negative regulator in C17.2 NSCs, restricting excessive cellular proliferation by inhibiting the Notch1 signaling pathway. These findings reveal a novel mechanism by which Pin1 maintains proliferation homeostasis during the development of embryonic NSCs.

Abstract:Objective: To investigate the diagnostic value of impulse oscillometry (IOS) in older patients with chronic obstructive pulmonary disease (COPD). Methods: This single-center observational study enrolled 670 older patients with COPD and 101 healthy controls who attended the First Affiliated Hospital of Nanjing Medical University between September 2019 and August 2023. All participants underwent IOS followed by spirometry. Demographic characteristics, IOS parameters, and spirometric indices were collected. IOS measurements were performed in strict accordance with international and Chinese guidelines. Respiratory system resistance at 5, 10, and 20 Hz (R5, R10, and R20), respiratory system reactance at 5, 10, and 20 Hz (X5, X10, and X20), the difference between R5 and R20 (R5-R20), and resonant frequency (Fres) were recorded and converted to Z scores. Spearman correlation analysis, generalized linear models with a gamma distribution and log-link function, and median quantile regression (τ=0.5) were used to evaluate the associations between IOS parameters and spirometric indices. Receiver operating characteristic (ROC) curve analysis was performed to assess diagnostic performance. Results: Compared with healthy controls, patients with COPD had significantly higher R5, R5-R20, and Fres and significantly lower X5 values (all P < 0.001). R5, R5-R20, and Fres were negatively correlated with the percentage of predicted forced expiratory volume in 1 second (FEV₁% predicted; R5: r=-0.500, P < 0.001; R5-R20: r=-0.584, P < 0.001; Fres: r=-0.546, P < 0.001). In contrast, X5 and X20 were positively correlated with FEV₁% predicted (X5: r=0.609, P < 0.001; X20: r=0.529, P < 0.001). After adjustment for age, sex, body mass index, and smoking index, R5-R20 was 34.3%, 119.2%, and 189.2% higher in patients with global initiative for chronic obstructive lung disease (GOLD) grades 2, 3, and 4, respectively, than in those with GOLD grade 1 (all P < 0.001). The corresponding increases in R5 were 15.2%, 49.3%, and 66.6% (all P < 0.001), whereas Fres increased by 16.0%, 42.1%, and 64.6%, respectively (all P < 0.001). X5 and X20 progressively decreased with increasing GOLD grade. The regression coefficients for X5 were -0.047, -0.186, and -0.328 for GOLD grades 2, 3, and 4, respectively, and those for X20 were -0.025, -0.059, and -0.089, respectively (all P < 0.001). A multivariable model combining Fres, R5, R20, X5, and X20 demonstrated improved diagnostic performance, with an area under the ROC curve of 0.803 (95% confidence interval: 0.761-0.845), a sensitivity of 59%, a specificity of 88%, and a Nagelkerke R² of 38%. Conclusion: IOS can effectively characterize airway resistance and the elastic properties of the respiratory system in older patients with COPD. A diagnostic model combining multiple IOS parameters showed moderate diagnostic performance and may serve as a useful adjunctive tool for the diagnosis of COPD in older adults.

Abstract:Objective: To investigate the association between plasma hypoxia-inducible factor-1α(HIF-1α) and moderate-to-large residual shunt(MLRS) after percutaneous patent foramen ovale(PFO) closure in patients with migraine and PFO. Methods: This prospective study included 45 migraine patients who underwent PFO closure at the Affiliated Hospital of Nantong University from August 2023 to August 2024. Patients were divided into MLRS and non-MLRS groups based on the presence or absence of MLRS. Clinical data and plasma HIF-1α levels were collected and compared before surgery, and 6 and 12 months after surgery. Multivariate logistic regression was used to identify potential factors for MLRS at 6 and 12 months. Receiver operating characteristic(ROC) curves evaluated predictive performance, and generalized estimating equation(GEE) assessed the interaction of HIF-1α with both antithrombin Ⅲ(AT-Ⅲ) and the neutrophil-to-lymphocyte ratio(NLR). Results: Plasma HIF-1α levels at 6 and 12 months postoperatively were significantly lower than preoperative levels(P < 0.01). Preoperative HIF-1α levels were significantly higher in the MLRS group than in the non-MLRS group at both follow-up time points(P < 0.05). Multivariate logistic regression showed that preoperative HIF-1α was a potential factor associated with MLRS at 6 and 12 months(P < 0.05). Decreased preoperative AT-Ⅲ levels were correlated with an increased risk of MLRS at 6 months postoperatively(P < 0.05), while elevated preoperative NLR levels were associated with an increased risk of MLRS at 12 months(P < 0.05).After Bootstrap correction, ROC analysis demonstrated that the area under curve(AUC) values of preoperative HIF-1α for predicting MLRS at 6 and 12 months were 0.823 and 0.825, respectively. The AUC for HIF-1α combined with AT-Ⅲ was 0.953(6 months), and with NLR was 0.937(12 months)(all P < 0.05). GEE revealed a significant association between HIF-1α and NLR(P < 0.05). Conclusion: Plasma HIF-1α levels show sustained decline after PFO closure. Preoperative plasma HIF-1α is a potential factor associated with postoperative MLRS, and its combination with AT-Ⅲ(at 6 months) and NLR(at 12 months) shows preliminary discriminative performance, respectively.

Abstract:Objective: To analyze the value of electrocardiogram (ECG) f-wave amplitude in predicting 1-year recurrence after radio frequency catheter ablation (RFCA) in elderly patients with persistent atrial fibrillation (PsAF). Methods: Patients aged ≥60 years who were diagnosed with PsAF and underwent RFCA in the First Affiliated Hospital of Nanjing Medical University from September 2014 to May 2022 were enrolled. Based on 1-year follow-up, patients were divided into two groups: the recurrence group and the non-recurrence group. The clinical characteristics of both groups were analyzed, and indicators showing significant differences were further examined using logistic regression analysis. Results: A total of 369 patients were included, among which there were 281 cases (76.15%) in the non-recurrence group and 88 cases (23.85%) in the recurrence group. There were no significant differences between the two groups in terms of age, body mass index, comorbidities, left ventricular end diastolic dimension, left ventricular ejection fraction, pulmonary artery pressure, Pro-BNP, uric acid, and low-density lipoprotein cholesterol, antiarrhythmic drugs (all P > 0.05). Compared with the non-recurrence group, the recurrence group had higher female ratio (39.77% vs. 26.69%, P=0.019), a longer duration of atrial fibrillation[15.5(6.00, 51.00)months vs. 9.00(3.00, 24.00)months, P < 0.001], lower f-wave amplitude in lead Ⅲ [0.07(0.06,0.08)mV vs. 0.09(0.08,0.11)mV,P < 0.001], lead avF[0.06(0.05,0.07)mV vs. 0.08(0.07,0.10)mV,P < 0.001], and lead V2[0.07(0.06,0.09)mV vs. 0.10(0.08,0.12)mV,P < 0.001], larger LAD[43.00(40.25,46.00)mm vs. 42.00(40.00,45.00)mm, P=0.039] and RAD[41.00(39.00, 43.75)mm vs. 40.00(39.00, 42.00)mm, P=0.038]. Logistic regression analysis identified atrial fibrillation duration as a risk factor for recurrence in elderly patients, while f-wave amplitudes in lead V2 and avF were independently negatively correlated with 1-year recurrence after radiofrequency ablation. Conclusion: The ECG f-wave amplitudes and atrial fibrillation duration may serve as predictors of the outcome of RFCA in elderly patients with PsAF.

Abstract:Objective: To establish a prediction model based on the clinical and dosimetric characteristics of patients with nasopharyngeal carcinoma (NPC), and assess its predictive efficacy for radiation-induced temporal lobe injury (TLI) following radiotherapy. Methods: We performed a retrospective analysis of the clinical data from 365 NPC patients(42 patients in the TLI group and 323 patients in the non-TLI group)who underwent radiotherapy-based comprehensive treatment in the radiotherapy department of our institution from June 2018 to November 2023. Clinical and dosimetric characteristics were collected, and univariate and multivariate logistic regression analyses were employed to identify independent risk factors associated with radiation-induced TLI. The random forest (RF) machine learning algorithm was used to construct a clinical feature model and a combined clinical and dosimetric feature model. Receiver operating characteristic (ROC) curves were plotted, and parameters such as the area under the ROC curve (AUC), sensitivity, and specificity were calculated. Calibration curves and decision curve analysis (DCA) were also conducted to evaluate the predictive performance of the models. Results: Univariate and multivariate logistic regression analyses revealed statistically significant differences in three features: T-stage (clinical characteristic), as well as D_{1 cm³} and V_70Gy (dosimetric characteristics)(all P < 0.05). The AUC values, sensitivity, specificity, and accuracy of the combined model and clinical model were 0.853 and 0.635, 66.67% and 85.71%, 86.38% and 39.94%, and 84.00% and 45.00%, respectively. The DeLong test indicated a statistically significant difference on predictive performance between combined and clinical models (P < 0.05). Both calibration curves and DCA results demonstrated that the combined model exhibited superior calibration and clinical net benefit. Conclusion: T-stage, D_{1 cm³}, and V_70Gy are independent predictors of radiation-induced temporal lobe injury. The combined model based on these three factors demonstrates high predictive capability for temporal lobe injury following NPC radiotherapy.

Abstract:Objective: Predictors were selected and a predictive model for surgical margin status in patients after radical prostatectomy for prostate cancer was constructed based on multiparametric magnetic resonance imaging (mp-MRI) combined with other clinical features with potential predictive capabilities. This provides a reliable predictive tool for surgical patients, thereby assisting clinical decision-making. Methods: A retrospective analysis was conducted on clinical data from 927 patients who underwent radical prostatectomy at the First Affiliated Hospital of Nanjing Medical University between January 2018 and June 2024. The data included baseline characteristics, preoperative serum biochemical indicators, mp-MRI imaging data, preoperative biopsy pathology results, and postoperative pathology results. The patients were randomly divided into a training set and a validation set in a 7:3 ratio. Univariate logistic regression analysis, multivariate logistic regression analysis, and backward stepwise regression analysis were performed on the training set data to identify independent predictors of prostate cancer margin status and to establish a predictive model. The predictive model was tested in the validation set for its discriminative ability, accuracy, and clinical utility. Results: Logistic regression analysis identified five independent predictors (P < 0.05): prostate-specific antigen density (PSAD), estradiol, PI-RADS score, number of lesions, suspected capsular invasion, and suspected lymph node metastasis. These predictors were used to construct a predictive model, and a nomogram was developed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were plotted for both the training and validation sets. The areas under the curve (AUC) were 0.897 (95%CI: 0.874-0.921) for the training set and 0.841 (95%CI: 0.793-0.888) for the validation set. The calibration curves for both sets closely aligned with the diagonal, with mean absolute errors (MAE) of 0.011 and 0.009, respectively, indicating no significant overfitting and demonstrating good generalization ability of the model. Decision curve analysis revealed that the model provides clinical net benefit. Conclusion: mp-MRI has significant predictive value for assessing surgical margin status in prostate cancer. The predictive model constructed in this study demonstrates strong predictive performance and can assist in clinical decision-making.

Abstract:This review systematically elucidates the metabolic mechanisms of essential trace element copper in humans, including absorption, distribution, storage, excretion, and homeostatic regulation. It emphasizes copper's role in participating in various biochemical reactions and maintaining protein structure and function through the redox conversion between cupric ions and cuprous state (or Cu+), as well as the pathological basis by which excessive free copper induces the production of reactive oxygen species and thereby triggers cellular damage. The review emphasizes the association of copper homeostasis dysregulation with multiple diseases, such as liver disorders, neurodegenerative conditions, cardiovascular diseases, and copper-related genetic diseases. It further explores copper's role in cancer biology, particularly its promotion of tumor initiation, proliferation, angiogenesis, and metastasis via signaling pathways, with a focus on the "copper proliferation"-mediated malignant transformation mechanisms. Additionally, recent advances and clinical potential of copper-targeted anticancer strategies, including copper chelators, ionophores, and complexes are discussed. Finally, the article addresses current challenges in copper-targeted therapies, such as therapeutic heterogeneity across different cancer types and patient populations, and the incomplete understanding of copper signaling networks. Future perspectives are provided, highlighting precision medicine approaches, combination therapies, and novel drug development, aiming to deepen the understanding of copper-related pathology and foster the development of innovative cancer treatments.

Abstract:Lipid droplet-mitochondria contact sites are important membrane contact sites that connect lipid storage, fatty acid oxidation, and mitochondrial homeostasis. As the liver is responsible for lipid synthesis, storage, oxidation, and export, it provides an ideal setting for investigating the roles of these contact sites in physiological adaptation and pathological remodeling. Growing evidence suggests that, both in chronic lipid overload-induced hepatic metabolic injury and in acute hepatic ischemia-reperfusion injury, lipid droplet-mitochondria contact sites are positioned at the intersection of lipid flux regulation, mitochondrial stress thresholds, and inflammatory injury amplification. During the early stage of metabolic stress, moderate lipid droplet formation and lipid droplet-mitochondrial coupling may facilitate lipid sequestration, fatty acid partitioning, and energy adaptation. However, under persistent lipid burden or reperfusion-associated oxidative stress, a mismatch between lipid droplet mobilization and mitochondrial uptake/oxidative capacity may lead to amplified lipotoxicity, reactive oxygen species bursts, mitochondrial DNA leakage, and sterile inflammation. In recent years, advances in super-resolution imaging, proximity labeling and spatial proteomics have promoted a shift in this field from morphological colocalization studies toward closed-loop analysis of structure, composition, and function. This review summarizes the structural basis and functional heterogeneity of lipid droplet-mitochondria contact sites, as well as their roles in hepatic metabolic injury and ischemia-reperfusion injury, and discusses their translational potential as disease stratification markers and therapeutic targets.

Abstract:Glioblastoma(GBM)exhibits limited response to immunotherapy,and conventional explanations based on the expression levels of immune-related molecules such as programmed death ligand 1(PD-L1),major histocompatibility complex class Ⅰ(MHC-Ⅰ),and cluster of differentiation 47(CD47)have proven insufficient to fully elucidate its immune evasion and therapy resistance mechanisms.Evidence indicates that GBM immune escape depends not only on the abundance of these molecules but also on their post-translational modification(PTM)-mediated regulation of membrane surface homeostasis,including protein maturation,plasma membrane delivery,surface retention,endocytic recycling,degradation,and extracellular vesicle(EV)export.Within this framework,“immune visibility”can be defined as the functional surface state in which tumor cells and their released EVs are recognizable,accessible,and susceptible to immune detection,engagement,killing,or phagocytosis in specific spatial and temporal contexts.This review emphasizes the regulatory roles of PD-L1,MHC-Ⅰ,CD47,and EVs in adaptive immune evasion,innate immune escape,and distributed immunosuppression in GBM,and evaluates their translational potential as dynamic biomarkers and targets for combination therapy.The proposed framework suggests that precision immunotherapy research in GBM should shift from static expression assessment to integrated evaluation of membrane surface availability,PTM status,and EV-mediated output,while further addressing upstream regulatory nodes that govern protein maturation,trafficking,stability,and vesicle release for mechanism-based therapeutic interventions.

Abstract:Fibroblast growth factor（FGF）and fibroblast growth factor receptor（FGFR）signaling pathways are key molecular hubs that regulate cell proliferation, differentiation, migration, and survival. They play a central role in various physiological processes such as embryonic development, tissue repair, and metabolic homeostasis. Abnormal activation of this pathway, driven by genetic abnormalities such as mutations, amplification, or chromosomal rearrangements in FGFR family genes（FGFR1-4）, has become an important oncogenic factor in the development of various malignant tumors. Patients carrying such variations generally have a poorer overall survival prognosis. In recent years, with the deepening of the concept of precision medicine and the popularization of high-throughput sequencing technology, new drug development targeting FGFR variations has made continuous progress. Various small molecule inhibitors have been approved for the treatment of tumor patients with specific FGFR gene abnormalities, significantly improving the prognosis of these patients. This article aims to explore the correlation between the FGFR signaling pathway and tumor occurrence and development in tumor patients, as well as the treatment options for tumor patients with FGFR signaling pathway variations, and focuses on the new progress in FGFR-targeted therapy.

Abstract:Melanoma is a kind of malignant skin cancer with a high mortality rate. Currently, the treatment of advanced melanoma remains a challenging issue as conventional treatments such as surgery, chemotherapy and radiotherapy offer limited benefits. Sonodynamic therapy(SDT) offers advantages such as high efficiency, simplicity, and less invasiveness. However, a major limitation is the difficulty in identifying suitable sonosensitizers that can ensure effective treatment outcome. With the gradual development of nanomedicine technology, the synthesized nano-sonosensitizers can resolve the limitations of SDT and enhance the therapeutic efficacy, making SDT a promising novel approach for the treatment of advanced melanoma. This article aims to review recent advances in sonosensitizers for sonodynamic therapy of melanoma and evaluate their therapeutic effects.

Abstract: