BACKGROUND:Steroid-induced osteonecrosis of the femoral head(SANFH)is a severe orthopedic disease characterized by interruption of the blood supply to the femoral head and necrosis of subchondral bone,leading to joint dysfunction.Long-term use of glucocorticoids is the main cause of SANFH,and its pathogenesis involves multiple factors,including intravascular coagulation and osteocyte apoptosis.Vascular endothelial growth factor A(VEGF-A),as a key angiogenic factor,has potential value in the treatment of SANFH.OBJECTIVE:To summarize the mechanisms of action of VEGF-A in SANFH,including its progress in promoting angiogenesis,anti-apoptosis,and lipid metabolism regulation,and to discuss the prospects for clinical application of VEGF-A targeted therapy.METHODS:Literature related to VEGF-A targeted regulation of angiogenesis in the treatment of SANFH was identified through searches of PubMed,Web of Science,CNKI,and WanFang databases from database inception to November 2024.After quality assessment,71 articles were selected,data were extracted by independent researchers,and disagreements were resolved through group discussions.RESULTS AND CONCLUSION:(1)VEGF-A binds to its receptors VEGFR-1 and VEGFR-2,activating downstream signaling pathways that promote the proliferation,migration,and angiogenesis of endothelial cells.Therefore,it can promote the formation of collateral circulation and improve blood supply to the area of bone necrosis.(2)Reduced expression of VEGF-A may lead to a decrease in the number of blood vessels within bone tissue,exacerbating the ischemic state of the femoral head.Furthermore,VEGF-A has anti-apoptotic effects and reduce apoptosis in osteocytes and bone marrow cells,thus protecting bone tissue.(3)The role of VEGF-A in regulating lipid metabolism and inflammatory responses,as well as promoting the osteogenic differentiation of bone marrow mesenchymal stem cells,provides a new perspective for the treatment of SANFH.(4)The development of VEGF-A protein delivery systems,such as lipid nanoparticles and exosome-based delivery systems,offers new possibilities for the clinical application of VEGF-A.(5)The research progress of VEGF-A in SANFH treatment has laid a solid foundation for the development of new treatment strategies and has opened up new avenues for future research directions and clinical applications.(6)With further clarification of the mechanisms of action of VEGF-A and continuous advancements in delivery technologies,more effective treatments will be provided for SANFH patients,improving their prognosis.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is complex,involving vascular endothelial injury,osteocyte apoptosis,inflammatory responses,and bone metabolism disorders.MicroRNAs(miRNAs),as key regulators of gene expression,play an important role in steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To comprehensively analyze the regulatory role of miRNAs in steroid-induced osteonecrosis of the femoral head and to evaluate their potential as biomarkers and therapeutic tools.METHODS:Relevant literature was retrieved from PubMed,Web of Science,CNKI,and WanFang databases using specific keywords,and articles were selected based on the inclusion and exclusion criteria.By reading titles,abstracts,or full texts,articles with poor relevance or repetitive content were excluded,and 76 articles were finally included for analysis.RESULTS AND CONCLUSION:miRNAs regulate gene expression by binding to the 3'untranslated region of target mRNAs,affecting cell differentiation,proliferation,apoptosis,and stress responses.Specific miRNAs such as miR-33-5p,miR-99a,miR-106b-5p,miR-155,miR-146a,and miR-21 play a central regulatory role in vascular injury,inflammatory responses,osteocyte differentiation,and apoptosis in steroid-induced osteonecrosis of the femoral head.Additionally,the expression patterns of miRNAs are closely related to the pathogenesis of steroid-induced osteonecrosis of the femoral head,showing potential as biomarkers.Although miRNAs shows great potential as biomarkers in therapeutic strategies,the current limitation of sample size and lack of multi-population validation restrict the universality and reliability of the results.Moreover,the efficacy and safety of miRNA therapeutic strategies(including off-target effects and delivery issues)remain major challenges in realizing clinical applications.

BACKGROUND:Steroid-induced osteonecrosis of the femoral head(SANFH)is a severe orthopedic disease characterized by interruption of the blood supply to the femoral head and necrosis of subchondral bone,leading to joint dysfunction.Long-term use of glucocorticoids is the main cause of SANFH,and its pathogenesis involves multiple factors,including intravascular coagulation and osteocyte apoptosis.Vascular endothelial growth factor A(VEGF-A),as a key angiogenic factor,has potential value in the treatment of SANFH.OBJECTIVE:To summarize the mechanisms of action of VEGF-A in SANFH,including its progress in promoting angiogenesis,anti-apoptosis,and lipid metabolism regulation,and to discuss the prospects for clinical application of VEGF-A targeted therapy.METHODS:Literature related to VEGF-A targeted regulation of angiogenesis in the treatment of SANFH was identified through searches of PubMed,Web of Science,CNKI,and WanFang databases from database inception to November 2024.After quality assessment,71 articles were selected,data were extracted by independent researchers,and disagreements were resolved through group discussions.RESULTS AND CONCLUSION:(1)VEGF-A binds to its receptors VEGFR-1 and VEGFR-2,activating downstream signaling pathways that promote the proliferation,migration,and angiogenesis of endothelial cells.Therefore,it can promote the formation of collateral circulation and improve blood supply to the area of bone necrosis.(2)Reduced expression of VEGF-A may lead to a decrease in the number of blood vessels within bone tissue,exacerbating the ischemic state of the femoral head.Furthermore,VEGF-A has anti-apoptotic effects and reduce apoptosis in osteocytes and bone marrow cells,thus protecting bone tissue.(3)The role of VEGF-A in regulating lipid metabolism and inflammatory responses,as well as promoting the osteogenic differentiation of bone marrow mesenchymal stem cells,provides a new perspective for the treatment of SANFH.(4)The development of VEGF-A protein delivery systems,such as lipid nanoparticles and exosome-based delivery systems,offers new possibilities for the clinical application of VEGF-A.(5)The research progress of VEGF-A in SANFH treatment has laid a solid foundation for the development of new treatment strategies and has opened up new avenues for future research directions and clinical applications.(6)With further clarification of the mechanisms of action of VEGF-A and continuous advancements in delivery technologies,more effective treatments will be provided for SANFH patients,improving their prognosis.

BACKGROUND:The pathogenesis of steroid-induced osteonecrosis of the femoral head is complex,involving vascular endothelial injury,osteocyte apoptosis,inflammatory responses,and bone metabolism disorders.MicroRNAs(miRNAs),as key regulators of gene expression,play an important role in steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To comprehensively analyze the regulatory role of miRNAs in steroid-induced osteonecrosis of the femoral head and to evaluate their potential as biomarkers and therapeutic tools.METHODS:Relevant literature was retrieved from PubMed,Web of Science,CNKI,and WanFang databases using specific keywords,and articles were selected based on the inclusion and exclusion criteria.By reading titles,abstracts,or full texts,articles with poor relevance or repetitive content were excluded,and 76 articles were finally included for analysis.RESULTS AND CONCLUSION:miRNAs regulate gene expression by binding to the 3'untranslated region of target mRNAs,affecting cell differentiation,proliferation,apoptosis,and stress responses.Specific miRNAs such as miR-33-5p,miR-99a,miR-106b-5p,miR-155,miR-146a,and miR-21 play a central regulatory role in vascular injury,inflammatory responses,osteocyte differentiation,and apoptosis in steroid-induced osteonecrosis of the femoral head.Additionally,the expression patterns of miRNAs are closely related to the pathogenesis of steroid-induced osteonecrosis of the femoral head,showing potential as biomarkers.Although miRNAs shows great potential as biomarkers in therapeutic strategies,the current limitation of sample size and lack of multi-population validation restrict the universality and reliability of the results.Moreover,the efficacy and safety of miRNA therapeutic strategies(including off-target effects and delivery issues)remain major challenges in realizing clinical applications.

Alzheimer's disease （AD） is a chronic neurodegenerative disorder with an unclear pathogenesis and currently no cure. It is characterized by a long disease course， diverse symptoms， and a persistent， difficult-to-treat nature， which greatly affects the quality of life of elderly patients. Traditional Chinese medicine （TCM） offers significant advantages in the treatment of AD， featuring multi-component， multi-target， and multi-pathway characteristics， with few adverse reactions and good safety. Angelica sinensis is a commonly used medicinal herb. As a frequently used clinical medicine for nourishing and activating blood， it shows significant efficacy in treating blood deficiency syndrome. In recent years， studies have revealed that A. sinensis exhibits significant activity in the prevention and treatment of AD. It contains various active components such as organic acids， volatile oils， and polysaccharides， and possesses pharmacological effects including anti-inflammatory， antioxidant， hepatoprotective， and neuroprotective properties. This article summarizes and outlines the mechanisms of A. sinensis and its compound formulas in the prevention and treatment of AD， providing a reference for its clinical application and the treatment of AD.

ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Background and purpose:Thyroid cancer is the most common malignant endocrine tumor,particularly prevalent among the Asian population.The overall survival for thyroid cancer patients is relatively high,but there are significant survival differences among patients.Based on long-term hospital-based cancer registry database,this study analyzed the 10-year observed overall survival(OS)rate of thyroid cancer cases and the distribution of causes of death,providing real-world evidences to further survival management of thyroid cancer in China.Methods:A total of 55343 thyroid cancer patients who underwent treatment at Fudan University Shanghai Cancer center from 2005 to 2021 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was October 31,2024.Kaplan-Meier method was applied in evaluating the OS rate,and survival data were described by different subgroups as age group,gender,treatment period,tumor staging and pathological characteristics.The standardized mortality ratio(SMR)and absolute excess risk(AER)were calculated using general Shanghai population as the reference,and the mortality risk was described by gender,age at diagnosis and histological subtype.Results:With a median follow-up time of 63.01 months,the overall 1-,3-,5-and 10-year OS rates of thyroid cancer patients were 99.67%(95%CI:99.62%-99.72%),99.11%(95%CI:99.03%-99.19%),98.48%(95%CI:98.36%-98.60%)and 95.81%(95%CI:95.50%-96.11%),respectively.The 10-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 97.99%(95%CI:97.70%-98.28%),89.80%(95%CI:87.24%-92.37%),77.84%(95%CI:70.76%-84.92%)and 62.95%(95%CI:55.37%-70.54%),respectively.The differences in OS among patients with different age,gender and histological classification were significant.1256(2.27%)deaths occurred,of which 18.63%,50.88%and 7.32%were attributable to thyroid cancer,other cancers and cardiovascular disease(CVD),respectively.Compared with the general population,patients with different subtypes of thyroid cancer had higher all-cause mortality rates,progressively increasing with papillary,follicular,medullary and anaplastic thyroid carcinoma/poorly differentiated carcinoma.Compared with general population,the death risk was 2.24 times higher in papillary thyroid cancer patients(95%CI:2.06-2.44),9.94 times higher in follicular thyroid cancer patients(95%CI:6.79-14.09),12.16 times higher in medullary thyroid cancer patients(95%CI:8.05-17.69),and the highest risk was observed in patients with anaplastic thyroid carcinoma/poorly differentiated carcinoma[SMR=79.67(95%CI:58.38-106.31),AER=766.01/1 000 person-years].Conclusion:The 10-year long survival data and cause of death for thyroid cancer patients with different histological types were reported in China based on a large single institution hospital-based cancer registry database.Staging and histological characteristics were the most important factors directly affected the survival.Early diagnosis and individualized treatment are crucial for improving prognosis.

Objective To analyze white matter hyperintensities(WMH)and 11C-CFT PET/CT characteristics in patients with PD,and explore their relationship.Methods A total of 84 PD pa-tients admitted to our department between March 2021 and March 2025 were retrospectively en-rolled,and they were divided into young group(33 cases)and elderly group(aged＞65 years,51 cases)and also into non-WMH group(22 cases)and WMH group(62 cases)based on the severity of WMH.The degree of white matter lesions was scored,including periventricular white matter hyperintense(PVH)score and deep white matter hyperintense(DWMH)score.All patients un-derwent head MRI and 11C-CFT-PET/CT scanning.The T/N value and asymmetry index were calculated.Results The elderly PD patients exhibited significantly advanced age and higher H-Y stages,but lower T/N values of affected side of caudate nucleus,contralateral caudate nucleus,affected side of anterior putamen,contralateral anterior putamen and contralateral posterior puta-men,and posterior putamen asymmetry index than the young patients(P＜0.05,P＜0.01).Simi-lar results were observed in the WMH group when compared with the non-WMH group(P＜0.05,P＜0.01).The PVH score was negatively correlated with the T/N values of affected side of caudate nucleus(r=-0.282,P=0.009),contralateral caudate nucleus(r=-0.215,P=0.049),affected side of anterior putamen(r=-0.249,P=0.022),contralateral anterior putamen(r=-0.280,P=0.010)and contralateral posterior putamen(r=-0.285,P=0.009),and DWMH score was also negatively correlated with the T/N values in the affected side of caudate nucleus and affected side of anterior putamen(P＜0.05).Conclusion Both age and disease severity impact WMH and dopaminergic system in PD patients.A higher WMH load is associated with dopamin-ergic neuronal damage.

Background and purpose:The microphthalmia-associated transcription factor(MITF)plays a complex role in melanoma pathogenesis and progression.It is known to regulate multiple processes both in melanocytes and melanoma cells.While numerous studies have explored MITF in cutaneous melanoma(CM),research in acral melanoma(AM)is still limited.This study retrospectively analyzed the correlation between MITF expression and clinical,pathological characteristics and prognosis in AM patients,providing a basis for prognosis evaluation and personalized treatment plan formulation for patients.Methods:Patients who underwent primary resection of AM at Fudan University Shanghai Cancer Center from March 2008 to February 2022 were included.All surgical samples were diagnosed by clinical histopathology and used to construct the tissue microarray(TMA).This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:2203-ZZK-69-3).Cutting complete tissue microarray and evaluating MITF expression levels by immunohistochemistry(IHC)staining were carried out.The results were independently assessed and scored by three pathologists.Clinical and pathological data were collected from the hospital's electronic medical record system,and each patient's data was matched to their corresponding tissue sample on the chip.Patients were stratified into two groups based on MITF expression levels.Statistical analyses were performed to assess differences in clinical,pathological characteristics and survival outcomes between these two groups.Results:A total of 137 AM patients were included.MITF expression was significantly associated with T stage,N stage,American Joint Committee on Cancer(AJCC)stage,clark level,sentinel lymph node status,and presence of ulceration.Among these,N stage and ulceration were independent risk factors for high expression of MITF after adjusting for confounding factors.Survival analysis showed that AM patients with high MITF expression or higher T stage were associated with shorter disease-free survival(DFS).Patients with high MITF expression showed no significant difference in overall survival(OS)between observation or cytokine therapy and adjuvant immune checkpoint inhibitor(ICI)therapy,whereas those with low MITF expression derived significant survival benefits from ICI treatment.Conclusion:A higher N stage or the presence of ulceration indicates high MITF expression in tumor cells,with high MITF levels serving as a warning signal for early recurrence,metastasis,and even death.Patients with low MITF expression could receive improved OS with early adjuvant ICI therapy.MITF could not only serve as an auxiliary diagnostic marker for melanoma but also provide a basis for clinical prognosis assessment and the formulation of personalized treatment plans.