Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2％,synovial sarcoma 3.8％,leiomyosarcoma 40.7％,malignant peripheral nerve sheath tumor 3.8％,myxofibrosarcoma 9.6％,pleomorphic sarcoma 19.9％,P=0.001),tumor necrosis(none 38.8％,focal necrosis 20.8％,moderate necrosis 33.8％,extensive necrosis 6.6％,P=0.010),and tumor metastasis(no metastasis 67％,metastasis 33％,P＜0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|＞1.0 and adjusted P value＜0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|＞2.0 and adjusted P value＜0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2％,synovial sarcoma 3.8％,leiomyosarcoma 40.7％,malignant peripheral nerve sheath tumor 3.8％,myxofibrosarcoma 9.6％,pleomorphic sarcoma 19.9％,P=0.001),tumor necrosis(none 38.8％,focal necrosis 20.8％,moderate necrosis 33.8％,extensive necrosis 6.6％,P=0.010),and tumor metastasis(no metastasis 67％,metastasis 33％,P＜0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|＞1.0 and adjusted P value＜0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|＞2.0 and adjusted P value＜0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

BACKGROUND:Medial open wedge high tibial osteotomy is an effective procedure for preserving the knee joint in patients with medial compartmental osteoarthritis.Previous studies have demonstrated that the forgotten joint score provides a lower ceiling effect and consistency of medial open wedge high tibial osteotomy outcomes compared to traditional assessment tools. OBJECTIVE:To identify predictive factors associated with the occurrence of a forgotten joint after medial open wedge high tibial osteotomy. METHODS:117 patients with medial open wedge high tibial osteotomy who were treated at First Affiliated Hospital of Guangzhou University of Chinese Medicine were selected,including 35 males and 82 females,with an average age of 61 years.They were followed up for at least 2 years.Patients were divided into a forgotten joint group(n=28)and a non-forgotten joint group(n=89)by evaluating whether they achieved forgotten joint after surgery.Univariate and multivariate logistic regression analyses were performed with preoperative patient characteristics and surgery-related factors as potential predictors. RESULTS AND CONCLUSION:(1)There were significant differences in the proximal medial tibial angle between the two groups before surgery(P<0.05).There were significant differences in the forgotten joint score,Knee Injury and Osteoarthritis Outcome Score,knee society knee score,function score,and patients joint perception between the two groups after surgery(P<0.05).There was a significant difference between the hip-knee-ankle angle and the medial proximal tibial angle after operation(P<0.05).(2)Univariate Logistic regression analysis showed that the medial proximal tibial angle had a significant influence on the forgotten joint before operation[OR=0.755,95%CI(0.635-0.897),P<0.001].There were significant effects on the forgotten joint of hip-knee-ankle angle and medial proximal tibial angle[OR=1.546,95%CI(1.242-1.924),P<0.001;OR=0.815,95%CI(0.713-0.931),P=0.003].(3)Multivariate logistic regression analysis showed that preoperative K-L grade 1 was a favorable factor for obtaining forgotten joints.Preoperative medial proximal tibial angle and postoperative hip-knee-ankle angle were independent predictors of forgetting joints,and they had a curvilinear relationship with the probability of achieving forgetting joints.When preoperative medial proximal tibial angle increased by 1°,the probability of achieving a forgotten joint decreased by 27.7%[OR=0.723,95%CI(0.593-0.882),P<0.001].Conversely,when postoperative hip-knee-ankle angle increased by 1°,the probability of achieving a forgotten joint increased by 46.4%[OR=1.464,95%CI(1.153-1.860),P=0.002].(4)The results showed that patients with preoperative knee osteoarthritis K-L grade 1,small medial proximal tibial angle(<85.5°),and large postoperative hip-knee-ankle angle(>176.0°)were predictors of forgotten joint.

Objective To analyze clinical prognosis, risk factors and predictive indexes of hyperkalemia in recipients after heart transplantation. Methods Clinical data of 158 recipients were retrospectively analyzed. According to the serum potassium levels within postoperative 1-year follow-up, all recipients were divided into the normal serum potassium level group (n=83), hyperkalemia group (n=43) and severe hyperkalemia group (n=32). The incidence and prognosis of hyperkalemia after heart transplantation were summarized. The risk factors and predictive indexes of hyperkalemia after heart transplantation were identified. Results The incidence of hyperkalemia and severe hyperkalemia within postoperative 1 year was 47.5%(75/158) and 20.3%(32/158), respectively. In the severe hyperkalemia group, the fatality was 16%(5/32), higher than 8%(7/83) in the normal serum potassium level group and 7%(3/43) in the hyperkalemia group. The mean serum creatinine (Scr) within 6 months before heart transplantation, the final total bilirubin level before heart transplantation, postoperative hemodialysis time, the Scr level and N-terminal pro-brain natriuretic peptide level at postoperative 1 d were the independent risk factors for hyperkalemia following heart transplantation (all P < 0.05). The mean Scr level within 6 months before heart transplantation, postoperative hemodialysis time, and Scr levels at postoperative 1 and 7 d could be used to predict postoperative severe hyperkalemia. Conclusions The recipients with severe hyperkalemia after heart transplantation obtain poor prognosis. The mean Scr level within 6 months before heart transplantation, the final total bilirubin level before heart transplantation, postoperative hemodialysis time, and the Scr level and N-terminal pro-brain natriuretic peptide level at postoperative 1 d are the independent risk factors for hyperkalemia after heart transplantation. Perioperative Scr level and postoperative hemodialysis time may be used to predict the incidence of severe hyperkalemia within 1 year after heart transplantation.

Parkinson disease （PD） is a common neurodegenerative disease. Cognitive dysfunction seriously affects the quality of life of patients with PD， increasing their family burden. Currently， there are no clinically identified biomarkers to assist with the early diagnosis of cognitive impairment in patients with PD. Event-related potential P300 is a sensitive electrophysiological indicator to detect early insidious cognitive decline in PD. This article reviews the diagnostic value and clinical application of P300 for cognitive impairment in patients with PD.

Objective:To explore the risk factors and follow-up outcomes of pediatric heart transplantation(HT).Methods:Between January 2018 and June 2022, perioperative data are retrospectively reviewed for 41 pediatric HT recipients aged <18 years and donor-recipient weight data for infants aged under 3 years at Guangdong Provincial People's Hospital.Perioperative survivors are followed up until August 31, 2022 through out patient visits and telephone calls.Postoperative survivals are examined by Kaplan-Meier method and possible risk factors for perioperative survival identify with Logistic regression.Results:There are 22 boys and 19 girls with a median age of 120(58~138)months.After preoperative adjuvant therapy of extracorporeal membrane oxygenation(ECMO), 8 cases had a successful transition to HT and 2 children underwent ABO incompatible(ABOi)HT.Six children aged under 3 years had a donor-recipient weight ratio of 2.95.Among 17 children, there are one or more complications, including continuous renal replacement therapy(CRRT, 9 cases, 21.95%), tracheotomy (3 cases, 7.32%), delayed chest closure or redo of sternotomy(6 cases, 14.63%)and acute graft dysfunction(4 cases, 9.76%). Five children died during perioperative period.The possible risk factors for perioperative mortality include preoperative ECMO assistance[ HR: 32.00, 95% CI: (2.83~361.79), P<0.05], preoperative CRRT[ HR: 11.33, 95% CI: (1.15~111.69), P<0.05] and total bilirubin [ HR: 1.02, 95% CI: (1.002~1.040), P<0.05]. During follow-ups, one child died from Epstein-Barr virus (EBV)associated post-transplant lymphoproliferative disease; another case of EBV-associated hepatic leiomyoma underwent transcatheter arterial embolization.With an overall survival rate of 85.37%, the cumulative survival rate is 96.97% for children without preoperative ECMO assistance( P<0.05). Postoperative mortality rate spiked markedly in children with preoperative ECMO assistance ( P=0.0013). However, follow-up results of perioperatively survivors indicate that preoperative usage of ECMO will not affect follow-up survival( P=0.53). In ABOi group or infants aged under 3 years, no mortality occurres postoperatively or during follow-ups. Conclusions:In infant aged under 3 years, the strategies of ABOi HT and large-weight donor HT are both safe and effective and it has no effect upon perioperative and follow-up survivals.Preoperative ECMO assistance, total bilirubin and preoperative use of CRRT are risk factors for perioperative survival.