Objective:To explore the effects of hyperoxic environments on renal metabolites to understand the potential mechanisms that contribute to pathologic retinal vascular neovascularization and renal injury through metabolomic studies in a mouse model of oxygen-induced retinopathy (OIR) model.Methods:Sixteen C57/B6J mice pups born to day 7 (P7) were randomly and equally divided into an OIR model group and a normal control group using a randomized numerical table of mother mice.Mice were reared standardly from birth until day 7 (P7), then mice and their mother mice in the OIR group were placed in a hyperoxic (75±2)% chamber until day 12 (P12) and then reared normally.Mice in the normal control group were reared normally throughout.Mice in two groups were killed by carbon dioxide euthanasia on postnatal day 17 (P17). The mice retinal wholemount from the two groups were made and stained with isolectin B4 (IB4) to observe the morphology of retinal vessels, central non-perfusion area and pathological neovascularization.The kidney tissue of P17 mice was analyzed by liquid chromatograph mass spectrometer.After anticoagulant treatment, the whole blood of mice was centrifuged and precipitated, and the obtained plasma without cellular components was analyzed by targeted metabonomics.Mass spectral information was interpreted using metabolomics data processing software Progenesis QI v2.3.Overall differences in metabolic profiles were distinguished by unsupervised principal component analysis and orthogonal partial least squares analysis (OPLS-DA). The fold change and P values of metabolites were compared between the two groups.The variable importance of projection value>1 and P value<0.05 was used to screen out differential metabolites.Metabolic pathway enrichment analysis of differential metabolites was performed based on the KEGG database.The feeding and use of animals were strictly in accordance with the requirements of the Ethics Committee of Jinan University, and the research protocol was reviewed and approved by the Ethics Committee of Jinan University (No.20200401-54). Results:The IB4 staining of retinal wholemounts showed that the retinal blood vessels were evenly distributed in the P17 mice from control group.The peripheral retinal vessels were tortuous and disordered with a large non-perfusion area in central region in P17 mice from OIR group, and a large number of neovascularization clusters were formed at the junction of the nonperfusion area and the vascular area of the retina, showing strong fluorescent staining.The relative area of retinal nonperfusion area in OIR group was (25.16±3.50)%, which was significantly larger than (0.63±0.30)% in normal control group ( t=12.07, P<0.001). The OPLS-DA parameter R2X cum (0.578), interpretation rate R2Y cum (0.978) and prediction rate Q2 cum (0.857) values were all greater than 0.5, indicating that the OPLS-DA model had a good predictive ability.A total of 26 main differential metabolites were found, among which 17 were up-regulated and 9 were down-regulated, including glycerophospholipids (PC 20∶4(5Z, 8Z, 11Z, 14Z)/0∶0, PC 22∶6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/0∶0, PC 14∶1(9Z)/20∶2(11Z, 14Z), PE P-18∶0/20∶4(6E, 8Z, 11Z, 14Z)(5OH[S]), amino acid metabolites (arginine, ornithine, pipecolic acid, and hydroxylysine), purines (guanine, hypoxanthine, hydroxypurinol), and fatty acids (methyl 15-palmitate, 2, 6, 8, 12-tetramethyl-2, 4-tridecadien-1-ol), and so on.Differential metabolites were mainly enriched in ABC transporters (L-arginine, taurine, inositol, adenosine, N-acetyl-D-glucosamine, L-glutamine), aminoacyl-tRNA biosynthesis (L-isoleucine, L-proline, L-arginine, L-histidine, L-glutamine), arginine biosynthesis (L-arginine, L-ornithine, L-glutamine) metabolic pathways.The plasma targeted metabonomics showed that the differential amino acid metabolites were mainly enriched in metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine biosynthesis and metabolism, and ABC transporters. Conclusions:ABC transporter, aminoacyl-tRNA biosynthesis, and arginine biosynthesis metabolic pathways in OIR mice may participate in the pathological changes of renal injury and neovascularization in retinopathy of prematurity.

Objective To investigate the effects of eicosanoic acid(C20DC)on the proliferation and migration of human retinal endothelial cells(HRECs)and its mechanism.Methods The optimal working concentration of C20DC in human retinal pigment epithelium 19(ARPE-19)cells and HRECs was determined as 30 mg·L-1 and 25 mg·L-1,respec-tively.HRECs were divided into the C20DC treatment group(HRECs treated with C20DC)and the control group[HRECs treated with dimethyl sulfoxide(DMSO)].The effects of C20DC on the migration and proliferation of HRECs were detec-ted by cell proliferation and migration experiments.The molecular docking method was used to simulate the binding ability of C20DC to peroxisome proliferator-activated receptor δ(PPARδ).ARPE-19 cells were divided into the C20DC+ARPE-19 group(ARPE-19 cells treated with C20DC)and the DMSO+ARPE-19 group(ARPE-19 cells treated with DMSO).The ex-pression levels of PPARδ and angiopoietin-like protein 4(ANGPTL4)in ARPE-19 cells and ANGPTL4 protein in HRECs were detected using Western blot.The ANGPTL4 protein expression levels in ARPE-19 cells and HRECs were quantitatively analyzed using enzyme-linked immunosorbent assay(ELISA).Results Compared with the control group,the prolifera-tion and migration of cells in the C20DC treatment group significantly increased(both P＜0.05),and C20DC could stably bind to PPAR8(binding energy:-7.20 kcal·mol-1).Western blot showed that the expression level of ANGPTL4 protein in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group,and the difference was statistically sig-nificant(P＜0.05);there was no statistically significant difference in the expression level of PPARδ receptor protein be-tween the two groups(P＞0.05).The expression level of ANGPTL4 protein in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P＜0.05).ELISA quantitative analysis showed that the expression level of ANGPTL4 in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group(P＜0.001);the expression level of ANGPTL4 in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion C20DC can promote the expression of ANGPTL4 pro-tein by binding to PPARδ and thus increase the proliferation and migration of retinal related cells(HRECs and ARPE-19 cells).Its mechanism may be related to the increased angiogenesis in retinopathy of prematurity.

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 understand research hotspots and future development trends in the field of familial exudative vitreoretinopathy (FEVR) from 2014 to 2023.Methods:Relevant literature on FEVR was retrieved using the Web of Science Core Collection (SSCI and SCI-Expanded) from the Institute for Scientific Information. The bibliometric analysis software CiteSpace 6.2.R3 was used to analyze countries or regions, institutions, authors, co-cited references, and keywords.Results:A total of 316 FEVR-related articles were included. The annual number of publications in this field showed a fluctuating upward trend from 2014 to 2023, with the highest number of publications in 2022, 51 papers (16.14%, 51/316); and the lowest in 2015, 15 papers (4.75%, 15/316). China had the highest number of publications, with 137 papers (43.35%, 137/316). Among institutions, Shanghai Jiao Tong University ranked first with 43 papers, while Professor Zhao Peiquan from Xinhua Hospital of Shanghai Jiao Tong University, had the highest number of publications among authors, with 34 papers. The country with the highest betweenness centrality was the United States, 0.91; the institution was the Chinese Academy of Medical Sciences, 0.16; and the author was Ding Xiaoyan, 0.12. The 316 papers were clustered into four research areas: #0 clinical characteristics, #1 ndp, #2 norrie disease, and #3 retinopathy of prematurity. Keywords such as "Chinese patients," " TSPAN12," "variants," and "spectrum" remained highly frequent up to 2023. Conclusions:The number of publications on FEVR research from 2014 to 2023 show a growth trend, with Chinese research institutions and scholars contributing the most. Research on pathogenic genotypes and clinical phenotypes remains a crucial direction for future development.

Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.

Objective: To explore the value of an oral squamous cell carcinoma (OSCC) diagnostic model constructed by using principal component analysis (PCA) to analyze a database of differentially expressed genes in OSCC and to provide a reference for clinical diagnosis and treatment. Methods: RNA-seq expression data of OSCC and normal control samples were obtained from The Cancer Genome Atlas (TCGA) database, and then, normalized and differentially expressed genes (DEGs) were identified by R software. DEGs were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify their main biological characteristics. 70% of DEGs expression data in RNA-seq were randomly selected as the training set and 30% were selected as the test set. Then, the PCA method was applied to analyze the training set data and extract the principal components (PCs) related to the diagnosis of OSCC in order to construct a PCA model. Then, the receiver operating characteristic (ROC) curves of PCA models in the training set and the test set were respectively drawn, and the area under curve (AUC) was calculated to evaluate the accuracy of the PCA model in the diagnosis of OSCC. Results: RNA-seq expression data of OSCC and normal control samples obtained from TCGA database included 330 samples and 32 samples, respectively. Using false discovery rate (FDR) <0.001 and |log2 fold change| (|log2FC|) >4 as the thresholds, a total of 159 downregulated and 248 upregulated DEGs were identified, which were mainly enriched in cellular components such as intermediate fiber and melanosomal membrane, pigment and salivation-related biological processes and mainly involved in salivary secretion and tyrosine metabolism pathways (P.adjust<0.05 and Q<0.05). The DEGs were proposed as tumor markers for OSCC, and PCA analysis of the training set showed that the cumulative ratio of variance of PC1, PC2 and PC3: [including submaxillary gland androgen regulated protein 3B (SMR3B), proline rich 27 (PRR27), histatin 3 (HTN3), statherin (STATH), cystatin D (CST5), BPI fold containing family A member 2 (BPIFA2), proline rich protein Hae Ⅲ subfamily 2 (PRH2), keratin 35(KRT35), histatin 1 (HTN1), amylase alpha 1B (AMY1B)] were 0.873, 0.100 and 0.023, respectively, and the total weight of the three was 0.996. The PCA diagnostic model of OSCC was further constructed by combining the eigenvectors of the above three components. The ROC curves of the training set and test set showed that the AUC values of the PCA model were 0.852 and 0.844, respectively, which were higher than those of other single genes. Conclusion The OSCC diagnostic model based on the expression levels of SMR3B, PRR27, HTN3, STATH, CST5, BPIFA2, PRH2, KRT35, HTN1 and AMY1B constructed with the PCA method and DEGs has a high diagnostic advantage. This study provides a theoretical basis for the early genetic diagnosis of OSCC and the application of the PCA model in clinical diagnosis.

Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.

Objective To evaluate the implementation and effectiveness of syphilis prevention and control in Hubei Province from 2011 to 2020, to summarize the experience and practice, to analyze the existing problems and causes, and to study and put forward policy and strategy suggestions, so as to provide reference for formulating the national ^“14th five-year plan^” and carrying out the next step of prevention and control work. Methods The National STD Prevention and Control Management Information System, STD Prevention and Control New Media Health Service Platform, National AIDS Comprehensive Prevention Information System, and National Management Information System for the Prevention of AIDS, Syphilis, and Mother-to-Child Transmission of Hepatitis B were used to analyze and evaluate the completion of main prevention and control indicators in Hubei Province. Results Among the 16 evaluation indexes, 10 indexes including the effectiveness of syphilis promotion and training for various groups of people, the proportion of pregnant women undergoing syphilis testing in the monitoring and testing work, and the effectiveness of syphilis prevention and treatment, all met the requirements of the plan. In addition, some of the 5 indexes failed to meet the requirements of the plan. Conclusion Hubei Province has fairly fulfilled the work requirements of the Plan. It is still necessary to strengthen the syphilis prevention and control to ensure the urban pregnant women infected with syphilis and their infants to receive standardized STD diagnosis and treatment services, and the drug users in the drug maintenance treatment clinic to receive free syphilis testing, and to provide referral services for the syphilis antibody positive patients at AIDS voluntary counseling and testing points.

Objective:To investigate the value of visfatin in the differential diagnosis of benign and malignant breast tumors and the feasibility of visfatin as a molecular marker of breast cancer.Methods:A total of 195 breast cancer patients hospitalized in the Cancer Hospital of The University of Chinese Academy of Sciences from December 2017 to July 2018 were selected as the breast cancer group, all of them were women. 80 patients with benign breast diseases in the same period were randomly selected as the breast benign disease group, all of them were women. 80 female employees with normal physical examination in the same year were selected as the normal control group. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum level of visfatin. Logistic regression was used to analyze the relationship between visfatin and clinicopathological features of breast cancer. Receiver operating characteristic (ROC) curve was drawn to get area under curve (AUC) value, and the diagnostic efficacy was analyzed.Results:The serum visfatin level in breast cancer group was significantly higher than that in benign breast disease group and normal control group ( P<0.05). Univariate analysis showed that the serum visfatin level was related to lymph node metastasis, tumor node metastasis (TNM) stage and body mass index (BMI) (all P<0.05). The serum visfatin level was positively correlated with TNM stage and lymph node metastasis of breast cancer patients ( r=0.336, P=0.043; r=0.632, P=0.027, respectively). Multivariate regression analysis showed that lymph node metastasis was a risk factor for serum visfatin [ OR=1.098, 95% CI(1.073, 1.226), P=0.02]. According to the ROC curve of serum visfatin level in benign breast disease group and normal group, the AUC of serum visfatin were 0.652 and 0.701, respectively. When the Youden index was the highest, the sensitivity was 52.30% and 55.90% respectively, and the specificity was 73.10% and 75.0% respectively. Conclusions:Serum visfatin level can be used to distinguish benign and malignant breast cancer patients. It has a certain clinical value in the auxiliary diagnosis of breast cancer, and may be used as a potential molecular marker of breast cancer.

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.