Objective:To understand the current status, research hotspots, and future trends in the field of retinoblastoma (RB).Methods:Using the Web of Science Core Collection SSCI and SCI-Expanded as data sources, relevant RB literature from January 2015 to November 2024 was retrieved. The bibliometric analysis software CiteSpace 6.2.R6 was employed to perform visual analyses of countries/regions, institutions, journals, authors, co-cited references, and keywords.Results:A total of 5 042 relevant publications were identified. Annual publication numbers in this field consistently exceeded 400, peaking at 565 in 2021. The United States contributed the highest number of publications, with 1 600 articles (31.73%). Among institutions, Harvard University ranked first with 167 publications (3.31%). Abramson DH of Memorial Sloan Kettering Cancer Center published the most papers (75). Nature (United Kingdom) received the highest citation count (2 349). The highest betweenness centrality was observed for the United States (0.14) among countries/regions, Shanghai Jiao Tong University (0.21) among institutions, and Berry JL of Children’s Hospital Los Angeles (0.21) at the author level. Co-citation and keyword analyses revealed that RB research hotspots are shifting from a focus on basic molecular mechanisms, such as the cell cycle and RB protein, toward advanced therapeutic strategies, such as intra-arterial chemotherapy and nanoparticle-based drug delivery. Emerging keywords such as complexity, chemoresistance and carboplatin indicate that future studies will focus on optimising diagnosis and treatment. Conclusions:From 2015 to 2024, RB research displayed a sustained growth trend, with the United States and its institutions and scholars contributing the most publications. The research focus has shifted from the exploration of molecular mechanisms to the optimization of precise treatment strategies, among which the application of nanotechnology and the resolution of drug resistance mechanisms will become key breakthrough directions.

Fundus neovascularization is a significant cause of ocular diseases, mainly including retinal neovascularization and choroidal neovascularization. Anti-vascular endothelial growth factor therapy, though effective, has limitations such as a short half-life, non-responsiveness, and drug resistance. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key regulator of glycolysis, affects the generation of pathological blood vessels by modulating the metabolism of vascular endothelial cells. Small molecule inhibitors targeting PFKFB3 protein have been confirmed in animal and cell models to significantly inhibit pathological angiogenesis, showing good therapeutic potential. However, most of them are still in the preclinical research stage. In the future, it is necessary to further investigate the mechanism of PFKFB3 gene, optimize the specificity and safety of the inhibitors, and explore the effects of combining them with existing therapies, so as to provide new strategies for the treatment of fundus neovascular diseases.

Objective:To understand the current status, research hotspots, and future trends in the field of retinoblastoma (RB).Methods:Using the Web of Science Core Collection SSCI and SCI-Expanded as data sources, relevant RB literature from January 2015 to November 2024 was retrieved. The bibliometric analysis software CiteSpace 6.2.R6 was employed to perform visual analyses of countries/regions, institutions, journals, authors, co-cited references, and keywords.Results:A total of 5 042 relevant publications were identified. Annual publication numbers in this field consistently exceeded 400, peaking at 565 in 2021. The United States contributed the highest number of publications, with 1 600 articles (31.73%). Among institutions, Harvard University ranked first with 167 publications (3.31%). Abramson DH of Memorial Sloan Kettering Cancer Center published the most papers (75). Nature (United Kingdom) received the highest citation count (2 349). The highest betweenness centrality was observed for the United States (0.14) among countries/regions, Shanghai Jiao Tong University (0.21) among institutions, and Berry JL of Children’s Hospital Los Angeles (0.21) at the author level. Co-citation and keyword analyses revealed that RB research hotspots are shifting from a focus on basic molecular mechanisms, such as the cell cycle and RB protein, toward advanced therapeutic strategies, such as intra-arterial chemotherapy and nanoparticle-based drug delivery. Emerging keywords such as complexity, chemoresistance and carboplatin indicate that future studies will focus on optimising diagnosis and treatment. Conclusions:From 2015 to 2024, RB research displayed a sustained growth trend, with the United States and its institutions and scholars contributing the most publications. The research focus has shifted from the exploration of molecular mechanisms to the optimization of precise treatment strategies, among which the application of nanotechnology and the resolution of drug resistance mechanisms will become key breakthrough directions.

Fundus neovascularization is a significant cause of ocular diseases, mainly including retinal neovascularization and choroidal neovascularization. Anti-vascular endothelial growth factor therapy, though effective, has limitations such as a short half-life, non-responsiveness, and drug resistance. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key regulator of glycolysis, affects the generation of pathological blood vessels by modulating the metabolism of vascular endothelial cells. Small molecule inhibitors targeting PFKFB3 protein have been confirmed in animal and cell models to significantly inhibit pathological angiogenesis, showing good therapeutic potential. However, most of them are still in the preclinical research stage. In the future, it is necessary to further investigate the mechanism of PFKFB3 gene, optimize the specificity and safety of the inhibitors, and explore the effects of combining them with existing therapies, so as to provide new strategies for the treatment of fundus neovascular diseases.

Purpose/Significance To analyze the multidimensional interaction between the characteristics of traditional Chinese and western medicine in patients with type 2 diabetes mellitus and its influence on traditional Chinese medicine(TCM)syndrome differentia-tion.Method/Process Based on the real-world electronic medical record(EMR)data,the traditional association rule algorithm is im-proved,and the important TCM syndromes are screened out as dependent variables by increasing the respect index,and the logistic regres-sion algorithm is used to explore the influence of traditional Chinese and western medicine indexes on TCM syndromes.Result/Conclusion Based on 688 patients,112 association rules are obtained,of which 12 includes TCM syndromes.The respect of association rules between middle-earth stagnation syndrome and overweight/obesity is the highest,moreover,overweight/obesity patients have a higher prevalence rate of middle-earth stagnation syndrome.There is a strong correlation between middle-earth stagnation syndrome,peripheral neuropathy or hypertension and overweight/obesity.Patients with diabetic nephropathy are more likely to have qi and yin deficiency syndrome.

Objective:To explore the diagnostic performance of patella-tilt angle and congruence angle in episodic patellar dislocation (EPD) and the quantitative measurements of the patellar and femoral axial parameters as well as their correlation with and contributions to the patellofemoral joint alignment with the knee extended.Methods:A case control study was conducted to analyze the radiological data of EPD patients (EPD group, n=106) and patients without patellar instability (control group, n=106) admitted to Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from January 2016 to December 2019. Each group consisted of 55 females and 51 males with the age range of 14-45 years [(23.0±5.3)years], showing 1∶1 match. Axial parameters included patellar parameters (patellar width, patellar thickness, Wiberg angle and Wiberg index), femoral parameters [trochlear sulcus angle, trochlear sulcus depth, trochlear sulcus height, trochlear width ratio (lateral/medial), trochlear height ratio (lateral/medial), lateral trochlear inclination and trochlear groove medialization], and patellofemoral joint parameters (patellar tilt angle and congruence angle). The receiver operating characteristic (ROC) curve of patellofemoral joint parameters for the prediction of EPD was analyzed. Univariate analysis was performed to determine the difference of those axial parameters between the two groups. Pearson correlation analysis was used to identify the correlation between those bony parameters and patellofemoral joint parameters. Stepwise regression model was further established to determine the influencing factors and corresponding contributions for patellofemoral joint parameters. Results:When the optimal cut-off values of patellar tilt angle and congruence angle were 17.2° and 25.5°, the area under the ROC curve (AUC) for predicting EPD was 0.91 (95% CI 0.87-0.95, P<0.01) and 0.92 (95% CI 0.87-0.95, P<0.01), and the Youden index was 0.745 (sensitivity=83.96%, specificity=90.57%) and 0.717 (sensitivity=81.13%, specificity=90.57%). Univariate analysis showed that Wiberg index, femoral parameters and patellofemoral joint parameters were significantly different between the two groups (all P<0.01). For all patients, Pearson correlation analysis showed that patellar tilt angle was moderately to strongly correlated with Wiberg index, trochlear sulcus angle, trochlear sulcus depth, trochlear width ratio (lateral/medial), trochlear height ratio (lateral/medial) and lateral trochlear inclination ( r=0.51, 0.41, -0.62, 0.43, -0.49, -0.65, all P<0.01) and that congruence angle has a moderate correlation with trochlear sulcus angle, trochlear sulcus depth, trochlear width ratio (lateral/medial) and lateral trochlear inclination ( r=0.43,-0.59,0.38,-0.51, all P<0.01). For all patients, Stepwise regression model analysis showed that lateral trochlear inclination, trochlear sulcus depth, trochlear sulcus angle, Wiberg index and trochlear height ratio (lateral/medial) could explain 60% of the variation of patellar tilt angle ( R 2=0.60, P<0.01) and that trochlear sulcus depth, lateral trochlear inclination, trochlear groove medialization, trochlear sulcus angle and Wiberg index could explain 44% of the variation of congruence angle ( R 2=0.44, P<0.01). Conclusions:The patellar tilt angle and congruence angle are reliable quantitative indicators representing patellofemoral axial alignment, with a good diagnostic performance for EPD. Variations in the patellar and femoral bony structures of EPD patients are related to the patellofemoral axial alignment, with the axial parameters differently contributing to the patellofemoral alignment.

Objective:To investigate the levels of serum pyrolysis-related factors cysteine protease-1 (caspase-1) and interleukin-18 (IL-18) in patients with gestational diabetes mellitus (GDM) and their relationship with insulin resistance (IR) .Methods:A total of 102 GDM patients admitted to Kaifeng Traditional Chinese Medicine Hospital from Apr. 2019 to Mar. 2021 were selected as the GDM group, and 102 healthy pregnant women undergoing obstetric examination in the same period were included as the normal group. The age, gestational week, fasting insulin (FINS) , pre-pregnancy body mass index (BMI) , triglycerides (TG) , fasting blood glucose (FBG) , total cholesterol (TC) , and homeostatic model insulin resistance index (HOMA-IR) and other materials were compared between the GDM group and the normal group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum caspase-1 and IL-18; Pearson method was used to analyze the correlation between serum caspase-1 and IL-18 levels and HOMA-IR in GDM patients; Logistic regression method was used to analyze the influencing factors of GDM.Results:The levels of TG [ (2.94±0.99) mmol/L vs (2.09±0.70) mmol/L], FBG [ (5.87±1.94) mmol/L vs (4.90±1.67) mmol/L], TC [ (5.72±1.92) mmol/L vs (5.03±1.68) mmol/L], FINS [ (11.45±3.87) mIU/L vs (6.92±2.34) mIU/L], HOMA-IR [ (3.05±0.78) vs (1.51±0.40) ] and levels serum caspase-1 [ (86.27±28.78) pg/mL vs (40.98±13.54) pg/mL] and IL-18 [ (44.26±14.56) pg/L vs (30.45±10.12) pg/L] in the GDM group were higher than those in the normal group (t=7.080, 3.827, 2.731, 10.116, 17.743, 14.381, 7.866, P<0.05) ; the levels of serum caspase-1 and IL-18 in GDM patients were positively correlated with HOMA-IR ( r=0.518, 0.555, P<0.05) ; FBG, TG, FINS, HOMA-IR, caspase-1, IL-18 were risk factors affecting the occurrence of GDM (95% CI=1.578-3.826, 1.454-3.311, 1.477-3.405, 1.678-4.265, 1.406-3.141, 1.511-3.551, P<0.05) . Conclusions:The levels of serum caspase-1 and IL-18 in patients with GDM are relatively high, which are significantly related to IR. Caspase-1 and IL-18 may be potential targets for the treatment of GDM.

Background::Circular RNAs (circRNAs) are endogenous non-coding RNAs, some of which have pathological roles. The current study aimed to explore the role of circRNA BTG3-associated nuclear protein (circ-BANP) binding with let-7f-5p and its regulation of the toll-like receptor 4 (TLR4)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA).Methods::Circ-BANP, let-7f-5p, and TLR4 expressions in HCC samples were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Bioinformatics prediction, RNA pull-down assay, and dual luciferase reporter gene assay were used to analyze the relationships among circ-BANP, let-7f-5p, and TLR4. Huh7 cells were used to generate an in vitro model of residual HCC, defined as Huh7-H cells, which were transfected with either a plasmid or the sequence of circ-BANP, let-7f-5p, or TLR4. Expression of circ-BANP, let-7f-5p, and TLR4 mRNA was determined by RT-qPCR. TLR4, STAT3, p-STAT3, vascular endothelial growth factor A, vascular endothelial growth factor receptor-2, and epithelial-mesenchymal transformation (EMT)-related factors proteins were determined by Western blotting. Cell proliferation was determined by cell counting kit-8 and 5-Ethynyl-2’-deoxyuridine (EdU) assay and cell migration and invasion by Transwell assay. Animal studies were performed by inducing xenograft tumors in nude mice. Results::Circ-BANP and TLR4 mRNAs were upregulated in HCC tissues (the fold change for circ-BANP was 1.958 and that for TLR4 was 1.736 relative to para-tumors) and expression further increased following insufficient RFA (fold change for circ-BANP was 2.407 and that of TLR4 was 2.224 relative to para-tumors). Expression of let-7f-5p showed an opposite tendency (fold change for let-7f-5p in HCC tissues was 0.491 and that in tumors after insufficient RFA was 0.300 relative to para-tumors). Competitive binding of circ-BANP to let-7f-5p was demonstrated and TLR4 was identified as a target of let-7f-5p (P < 0.01). Knockdown of circ-BANP or elevation of let-7f-5p expression inhibited the TLR4/STAT3 signaling pathway, proliferation, invasion, migration, angiogenesis, and EMT in Huh7 and Huh7-H cells ( P < 0.01). The effects induced by circ-BANP knockdown were reversed by let-7f-5p inhibition. Overexpression of TLR4 reversed the impact of let-7f-5p upregulation on the cells ( P < 0.01). Silencing of circ-BANP inhibited the in vivo growth of residual HCC cells after insufficient RFA ( P < 0.01). Conclusions::Knockdown of circ-BANP upregulated let-7f-5p to inhibit proliferation, migration, and EMT formation in residual HCC remaining after insufficient RFA. Effects occur via regulation of the TLR4/STAT3 signaling pathway.

Objective:To observe the changes of macular morphology and best corrected visual acuity (BCVA) in children with retinopathy of prematurity (ROP) after single treatment of laser photocoagulation or intravitreal injection of ranibizumab (IVR) by optical coherence tomography angiography (OCTA).Methods:A cross sectional study was conducted.Fourteen cases (23 eyes) of ROP children with a treatment history aged 4-10 years were enrolled as the ROP group in Shenzhen Eye Hospital from April to August 2018, with 8 cases (16 eyes) of age-matched full-term children as control group.Among the ROP group, 9 cases (14 eyes) receiving photocoagulation were set as the photocoagulation group and 5 cases (9 eyes) receiving IVR as the injection group.The 3 mm×3 mm scanning mode of OCTA was adopted to measure the area of foveal avascular zone (FAZ), FAZ morphological index, superficial retinal vascular density (VD) and superficial retinal perfusion density (PD), and the B-scan mode was used to determine the central foveal thickness (CFT). BCVA of all children was recorded and analyzed.This study adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Shenzhen Eye Hospital (No.b-03). Written informed consent was obtained from guardians prior to any examination.Results:Compared with the control group, there was smaller area of FAZ, more irregular FAZ morphology and thicker CFT in the ROP group.The central fovea of macula in the laser photocoagulation group was shallow and almost indiscernible, and FAZ morphology was irregular.The FAZ area, FAZ morphological index, VD and PD in the ROP group were (0.09±0.08) mm 2, 0.51±0.25, (19.18±2.50)mm/mm 2 and 0.35±0.04, respectively, which were significantly lower than (0.32±0.08)mm 2, 0.68±0.07, (20.94±0.93)mm/mm 2, 0.38±0.02, respectively in the control group ( t=-8.03, -3.14, -3.02, -2.52; all at P<0.05). The CFT in the ROP group was (215.00±21.32) μm, which was significantly thicker than (164.29±20.20) μm in the control group ( t=8.91, P<0.05). There was no statistical difference in BCVA between the two groups ( t=0.16, P=0.87). The CET in the laser photocoagulation group was significantly thicker than that in the injection group ( t=3.50, P=0.01). Conclusions:There are obvious morphology changes of macula in ROP children with single treatment history of laser photocoagulation or IVR, while the BCVA is not significantly affected by the treatment.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.