Thirteen novel diterpenoids, comprising seven tiglianes (walliglianes G-M, 1-7), four rhamnofolanes (wallinofolanes A-D, 8-11), and two daphnanes (wallaphnanes A and B, 12 and 13), together with two known rhamnofolane diterpenoids (euphorwallside H and euphorwallside I, 14 and 15), were isolated and characterized from Euphorbia wallichii(E. wallichii). The chemical structures of these compounds were elucidated through nuclear magnetic resonance (NMR), mass spectrometry (MS), and quantum chemical calculations. Compounds 9 and 11 demonstrated protective effects against H₂O₂-induced BV-2 microglial cell damage. Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR, GSTP1, and SHBG.
Euphorbia/chemistry* ; Antioxidants/isolation & purification* ; Diterpenes/isolation & purification* ; Molecular Structure ; Mice ; Molecular Docking Simulation ; Animals ; Hydrogen Peroxide/toxicity* ; Cell Line ; Microglia/drug effects*

Objective:To analyze the clinicopathological characteristics and prognostic factors of patients with Castleman disease (CD).Methods:A retrospective case-series study was conducted. A total of 85 patients newly diagnosed with CD in the First Affiliated Hospital of Air Force Medical University between July 2007 and August 2024 were collected. Their clinical characteristics and prognostic factors were analyzed.Results:Among the 85 patients, 45 had unicentric Castleman disease (UCD) and 40 had multicentric Castleman disease (MCD). In the UCD group, females were more commonly affected (64.4%, 29/45), with a median age of onset of 39 years. The primary lesions were mainly located in the retroperitoneum, neck, abdomen, and axilla; and the hyaline vascular subtype was the predominant pathological type (69.4%, 25/36). In the MCD group, males were more frequently affected (62.5%, 25/40), with a median age of onset of 50 years; and the plasmacytic subtype was the main pathological type (68.2%, 15/22). Compared with UCD patients, MCD patients presented more systemic symptoms and signs [85.0% (34/40) vs. 13.3% (6/45), χ2 = 43.66, P < 0.001], splenomegaly [42.5% (17/40) vs. 2.2% (1/45), χ2 = 20.58, P < 0.001], hepatomegaly [25.0% (10/40) vs. 0 (0/45), χ2 = 10.46, P = 0.001], edema or effusion in serous cavity [67.5% (27/40) vs. 8.9%(4/45), χ2 = 31.40, P < 0.001], hematological system involvement [32.5% (13/40) vs. 0 (0/44), χ2 = 16.92, P < 0.001], and renal involvement [22.5% (9/40) vs. 2.3%(1/44), χ2 = 6.36, P = 0.012]. Laboratory findings showed that the levels of hemoglobin and albumin in MCD patients were lower than those in UCD patients, while white blood cell count in MCD patients was higher than that in UCD patients. Additionally, MCD patients exhibited elevated levels of C-reactive protein, interleukin-6, vascular endothelial growth factor, erythrocyte sedimentation rate, and ferritin compared to UCD patients (all P < 0.05). Among UCD patients, 40 cases underwent simple surgical resection, with no deaths during follow-up and the 5-year overall survival (OS) rate of 100.0%; among MCD patients, 34 cases received chemotherapy, 4 received siltuximab, 3 died during follow-up with a 5-year OS rate of 87.5%; and there was no statistically significant difference in OS between the MCD and UCD groups ( χ2 = 3.67, P = 0.055). Among MCD patients, the OS of those with renal involvement (9 cases) was worse than that of those without renal involvement (31 cases) ( χ2 = 8.39, P = 0.004). Conclusions:CD is a highly heterogeneous disorder. Surgical resection is the primary treatment for UCD, with a favorable prognosis. Chemotherapy is the main treatment for MCD, with a relatively poor prognosis.

Objective:To analyze the clinical characteristics of adverse reactions caused by dinutuximab β for the treatment of neuro-blastoma(NB)in China and to provide safety evidence for the rational use of dinutuximab β in clinical practice.Methods:Clinical data were retrospectively collected from 16 pediatric patients with NB who had been treated with dinutuximab β at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to November 2023,and the adverse reactions caused by dinutuximab β were summarized and analyzed.Results:The male-to-female ratio was 5:3 among the 16 children with NB.The retroperitoneum was the main initial site of involvement,accounting for 75%.Thirteen(81.25%)patients had high-risk NB.The adverse reactions caused by dinutuximab β mainly included decreased hemoglobin,fever,vomiting,and diarrhea.The inci-dence of adverse reactions was highest in the first course of treatment,and the median time of adverse reactions was 2-5 days.Conclu-sion:Targeted monitoring should be carried out at an early stage during dinutuximab β administration.Adverse reactions should be de-tected and managed early to ensure the safety of medication for children.

Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

Objective To explore the value of cranial CT perfusion imaging(CTP)parameters combined with head and neck CT angiography(CTA)in assessing collateral circulation status and predicting prognosis in acute ischemic stroke(AIS).Methods A retrospective analysis was carried out on 83 AIS patients who were treated in Taikang Xianlin Drum Tower Hospital from June 2018 to June 2023.CTP and head and neck CTA examinations were performed within 24 hours after admission.Digital subtraction angiography is the gold standard for assessing collateral circulation status in AIS patients.The general information of these patients was collected,and the patient's prognosis was evaluated using the modified Rankin scale through telephone or outpatient follow-up 90 days after the occurrence of AIS.Pearson or Spearman correlation was used to analyze the correlation between collateral circulation assessment and CTP parameters and head and neck CTA scores.The value of CTP parameters and head and neck CTA scores in predicting the prognosis of AIS patients was discussed using multivariate Logistic regression.Moreover,the receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTP parameters,head and neck CTA,and the combination for the prognosis of AIS patients.Results The cerebral blood volume(CBV),cerebral blood flow(CBF),and CTA score were higher,while mean transit time(MTT)and time to peak(TTP)were shorter in the good collateral circulation group than in poor collateral circulation group(P<0.05).The collateral circulation status in AIS patients was negatively correlated with CBV,CBF,and CTA score,while positively correlated with MTT and TTP(P<0.05).Compared with poor prognosis group,good prognosis group had higher CBV,CBF,CTA,and shorter MTT and TTP(P<0.05).Multivariate Logistic regression analysis identified MTT and TTP as risk factors for poor prognosis,and CBV,CBF,and CTA scores as protective factors for poor prognosis in AIS patients(P<0.05).The ROC results showed that the area under the curve(AUC)of CBV,MTT,CBF,TTP,CTA score and the combination to predict the prognosis of AIS patients were 0.897,0.864,0.835,0.920,0.918,and 0.979,respectively,showing better predictive performance of the combination than single index alone(Z=2.194,2.910,2.521,2.229,2.171;P<0.05).Conclusion CTP parameters combined with CTA may effectively assess collateral circulation in patients with AIS and is significant for prognosis prediction.

Objective:To determine the prevalence and associates of hyperuricemia (HUA) among the middle- and older-aged population of the island and mountainous areas in Taizhou City of Zhejiang Province.Methods:A cross-sectional study was conducted on individuals aged 45 and above in the island and mountainous area of Taizhou City. The study included questionnaires, physical examinations, and laboratory tests. Data were primarily collected on sociodemographic characteristics, chronic disease history, lifestyle factors, waist circumference, blood pressure, and serum uric acid levels. The association between hyperuricemia and these factors was analyzed by logistic regression.Results:A total of 971 individuals were included in the study, comprising 468 from island and 503 from mountainous area. The prevalence of hyperuricemia was 17.9%, with a significantly higher prevalence in the island area (25.6%) compared to the mountainous area (10.7%). Stratified by gender and age, differences in the prevalence of hyperuricemia between island and mountainous areas were observed in males aged 55 to 64, females aged 45 to 54, 55 to 64, 75 and above (all P<0.05). Multiple logistic regression analysis showed that high intake of sea food (>3 times/week) was positively associated with hyperuricemia ( OR=2.10, 95% CI:1.33-3.34). Furthermore, separate regionally stratified logistic regression analyses showed that in the island area, male gender ( OR=3.15, 95% CI:1.78-5.66), central obesity ( OR=2.38, 95% CI:1.46-3.93), and hypertriglyceridemia ( OR=2.00, 95% CI:1.22-3.30) were positively correlated with hyperuricemia (all P<0.05). In the mountainous area, the age group of 65 and above ( OR=3.50, 95% CI:1.09-12.50), male ( OR=6.79, 95% CI:2.87-17.81), those employed in enterprises and institutions ( OR=6.57, 95% CI:1.92-23.73) and hypertension ( OR=3.68, 95% CI:1.66-8.87) were positively correlated with hyperuricemia (all P<0.05). Conclusions:The prevalence of hyperuricemia among the middle- and older-aged population in the island of Taizhou City is significantly higher than that in the mountainous areas. Targeted comprehensive behavioral interventions such as routine screening of chronic diseases, low-fat diet, alcohol control, reduced seafood intake, enhanced exercise, weight management, and blood pressure control are warranted.

Objective:To construct a predictive model for postoperative delirium (POD) in patients undergoing gastrointestinal surgery using machine learning.Methods:This retrospective study used clinical data from patients who underwent gastrointestinal surgery at Subei People′s Hospital between September 2022 and April 2024. The entire dataset was randomly divided into the training and validation sets in an 8∶2 ratio. Multivariate logistic regression analysis was conducted to identify the factors influencing POD. Eleven machine learning models were established and compared. The performance of the models was validated using metrics, including accuracy, precision, recall, Youden′s index, F1 score, Matthews′ correlation coefficient, Kappa coefficient, log loss, and Brier score. Receiver operating characteristic and calibration curves were plotted to assess the discrimination and consistency of the model. Shapley additive explanations were used in Python for interpretative analysis of the model with the best predictive performance, and the importance of the feature parameters was ranked.Results:A total of 1, 785 patients were ultimately included, of which 833 (46.67%) experienced POD. The results of multivariate logistic regression analysis revealed that advanced age, lower preoperative serum calcium ion concentration, postoperative pulmonary infection, and higher preoperative systolic blood pressure were independent risk factors for POD in patients undergoing gastrointestinal surgery, while laparoscopic surgery was a protective factor ( P<0.05). Among the 11 machine learning models, the categorical feature gradient boosting model exhibited the best performance, with an area under the receiver operating characteristic curve of 0.82 (95% confidence interval 0.77-0.87). The ranking of feature importance indicated that age had the greatest contribution in predicting POD. Conclusions:The predictive model for POD established based on the categorical boosting algorithm has higher predictive efficacy and clinical application value in patients undergoing gastrointestinal surgery.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

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 experimentally validate clinical samples, analyze the mRNA expression of the FYVE domain containing phosphatidylinositol 3-phosphate 5 kinase ( PIKFYVE) gene, and its clinical significance based on the Cancer Genome Atlas (TCGA) database in hepatocellular carcinoma (HCC). Methods:Data information on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of non-tumorous liver tissues) were collected based on the TCGA database. Cox regression analysis and the Kaplan-Meier method were used to analyze the relationship between mRNA expression of the PIKFYVE gene and the clinical characteristics as well as survival prognosis in patients with HCC. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis with 24 kinds of immune cells. In addition, the mRNA expression level of the PIKFYVE gene and RAC-alpha serine/threonine-protein kinase ( AKT1), phosphatase and tensin homolog ( PTEN), protein kinase C alpha ( PRKCA), inositol polyphosphate-5-phosphatase ( INPP5D), phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1), inositol polyphosphate 4-phosphatase type II ( INPP4B) and phospholipase C beta 4 ( PLCB4) gene correlations were analyzed in HCC tissues. At the same time, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and non-tumor liver tissues from patients with HCC were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University. The histopathological observation was performed by HE staining. Immunohistochemistry was used to verify the expression levels of the PIKFYVE and Ki67 proteins in each clinical sample. The t-test was used for intergroup comparison of continuous data. The χ2 test and Wilcoxon rank sum test were used for intergroup comparison of enumeration data. The Kaplan-Meier method was used for survival analysis. Results:The expression level of the PIKFYVE gene was higher in the HCC tumor than that in normal liver tissue ( P<0.01). The overall survival time of patients was significantly longer in the low expression group than that in the high expression group ( HR=1.57, 95% CI: 1.10～2.25, P=0.014). The results of univariate Cox regression analysis showed that tumor stage, pathological grade, tumor status, residual tumor, and PIKFYVE expression level all had an effect on OS ( P<0.05). The PIKFYVE prognostic risk model had a proportionate score of HR=1.533 (95% CI: 1.077～2.181, P=0.018). Multivariate Cox risk regression analysis showed that the PIKFYVE prognostic risk model had a proportionate score of HR=1.481 (95% CI: 0.886～2.476, P=0.134) and an area under the receiver operating characteristic curve of 0.559, indicating that it had predictive value for survival prediction. The results of the correlation analysis showed that the expression level of PIKFYVE was strongly correlated with immune cell infiltration and TP53 ( P<0.01). The results of immunohistochemical staining showed that the expression level of PIKFYVE was significantly higher in HCC tissue samples than that in non-tumor liver tissues ( P<0.01), and was negatively correlated with the degree of differentiation. Conclusion:PIKFYVE, as an independent risk factor, is expected to be developed into a biomarker for clinical diagnosis, offering a reference for novel therapeutic agents in HCC.