Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective:To explore the value of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) of MRI in evaluating the response of osteosarcoma to neoadjuvant chemotherapy (NAC) in different cycles, and to analyze the diagnostic efficacy of each ADC and its difference.Methods:A total of 31 patients with pathologically confirmed osteosarcoma in the Nanjing Drum Tower Hospital, Nanjing University Medical School from January 2019 to December 2022 were retrospectively analyzed. All patients received NAC before surgery, and routine MRI and DWI were performed before and during chemotherapy. The ADC values were measured before, during and after chemotherapy (ADCpre, ADCmid, ADCpost), and the difference were calculated. According to whether the tumor necrosis rate was more than 90%, the patients were divided into good response group and poor response group. The differences of ADC values in each stage within the two groups were compared, and the differences of related parameters between the two groups were compared, and the diagnostic efficacy of each parameter in predicting tumor necrosis rate was analyzed by receiver operating characteristic(ROC) curve.Results:The ADC values of the two groups at different stages of NAC were compared. Except for the intermediate ADCmid and ADCpost in the poor response group ( P = 0.226), all the ADC values were statistical differences ( P<0.05). There were significant differences in ADCmid and ADCpost between the good response group and the poor response group (1.52 ± 0.39 vs. 1.39 ± 0.25, 1.65 ± 0.16 vs. 1.46 ± 0.44, P<0.05), but there was no significant difference in ADCpre between the two groups ( P>0.05). ROC curve showed that the area under the curve of ADCmid, ADCpost and △ADC3 (ADCpost -ADCpre) were 0.897, 0.810 and 0.714, respectively, and ADCmid had the best diagnostic efficiency. Conclusions:ADCmid, ADCpost and △ADC3 can be used to evaluate the efficacy of NAC in osteosarcoma. The ADCmid can provide some reference for the adjustment and improvement of clinical treatment.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective:To explore the expression of microRNA-3162-3p in different clinical stages of childhood primary immune thrombocytopenia(ITP)and its significance.Methods:Ninety-six children with ITP were enrolled and divided into new diagnosis group(n=40),persistent group(n=30)and chronic group(n=26)according to the course of disease.80 healthy children were selected as the control group.Peripheral blood mononuclear cells(PBMNC)of ITP children and healthy children were isolated and cultured,and the expression of microRNA-3162-3p in PBMNC of subjects was detected by real-time fluorescence quantitative PCR.The contents of IL-17,IL-23,IL-10 and TGF-β in PBMNC of subjects were determined by ELISA.The correlation between microRNA-3162-3p and platelet count,IL-17,IL-23,IL-10 and TGF-β was analyzed.Results:Compared with the control group,the expression of microRNA-3162-3p and IL-10 in PBMNC and platelet count of ITP children were significantly decreased(P＜0.05),while IL-17,IL-23 and TGF-β were significantly increased(P＜0.05).With the prolongation of the disease course,the expressions of microRNA-3162-3p and IL-10 in PBMNC and platelet count were significantly decreased(P＜0.05),while the expressions of IL-17,IL-23 and TGF-β were significantly increased(P＜0.05).The expression of microRNA-3162-3p in PBMNC was positively correlated with platelet count and IL-10(r=0.716,0.667),and negatively correlated with IL-17,IL-23,and TGF-β(r=-0.540,-0.641,-0.560).Conclusion:MicroRNA-3162-3p expression is significantly reduced in PBMNC of children with ITP,and is involved in the regulation of Th17/Treg imbalance,which can be used as a potential therapeutic target of ITP.

AIM To investigate the effects of stir-frying,processing with butter and carbonizing by stir-frying on oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis.METHODS The volatile oils and fatty oils were extracted by steam distillation method and Soxhlet extraction method,respectively,after which the extraction rates were determined.GC-MS was applied to analyzing the kinds and relative contents of oil components,after which cluster analysis was performed.RESULTS After the processing,the two medicinal materials demonstrated increased extraction rates of fatty oils and decreased extraction rates of volatile oils(except for processing with butter),the extraction rates of oil components in Gleditsiae sinensis Fructus were higher than those in Gleditsiae Fructus Abnormalis,and the reduced relative contents of toxic olefin benzene components were observable.CONCLUSION The kinds and relative contents of oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis exist obvious differences,the former displays better medicinal quality,whose processing mechanism in alleviating dryness and strength may contribute to the reduction of relative contents of toxic olefin benzene components.

Objective To investigate the evaluation effect of lung ultrasound (LUS) score on the severity and prognosis of severe pneumonia in children. Methods A total of 120 children with severe pneumonia admitted to the intensive care unit (ICU) of Anhui Provincial Children's Hospital from January 2020 to May 2023 were included in the study. Lung ultrasound examination, clinical pulmonary infection score (CPIS), pediatric critical illness score (PCIS), and oxygenation index (OI) were analyzed before and after treatment, and the levels of various indicators in children were compared. According to OI value, the children were divided into low-risk group (OI≥300, 84 cases) and high-risk group (OI < 300, 36 cases). Based on the analysis of the prognosis of the children, they were divided into survival group and death group. Pearson correlation analysis was used to analyze the correlation between LUS score and CPIS score, PCIS score, and OI. Receiver operating characteristic (ROC) curves were drawn to calculate the area under the curve, sensitivity, and specificity of LUS score in evaluating the prognosis of children. Results After treatment, both LUS score and CPIS score of 120 cases were lower than before treatment, while PCIS score and OI were higher than before treatment (P < 0.05). Before treatment, the LUS score and CPIS score in the low-risk group were lower than those in the high-risk group, while the PCIS score and OI were higher than those in the high-risk group (P < 0.05). Among the 120 children, 87 survived(survival group) and 33 died(death group). Before treatment, the LUS score and CPIS score in the survival group were lower than those in the death group, while the PCIS score and OI were higher than those in the death group (P < 0.05). LUS score was positively correlated with CPIS score and negatively correlated with PCIS score and OI (P < 0.05). The area under the curve of LUS score in evaluating the prognosis of children was 0.899, with sensitivity and specificity of 0.758 and 0.863, respectively. Conclusion Lung ultrasound score plays a guiding role in the evaluation of severity and prognosis of severe pneumonia in children, with high sensitivity and specificity in prognosis evaluation.

Objective To explore the pattern of early expression and secretion of tissue factor(TF)in vascular endothelial cells induced by heat stress.Methods Thirty SPF-rated C57BL/6 male mice were randomly divided into five groups:the control group and groups of indicated recovery time,including 0,3,6,and 9 h in room temperature after heat stress(n=6).Mice in the heat stress groups were exposed to an animal incubator to reach 42.5℃for core body temperature for heat stroke.We analyzed the histopathological changes in the liver,lung,and kidney tissues with HE staining.We measured the TF mRNA in mice tissues by RT-qPCR and the plasma concentration of TF in mice with a commercial ELISA kit.Human umbilical vein endothelial cells(HUVECs)were placed in a culture incubator to build an in vitro heat stress model.HUVECs were divided into five groups,including a control group and groups of indicated recovery time,including 0,3,6,and 9 h after heat stress.We quantified the expression of TF mRNA and protein in HUVEC cells by RT-qPCR,Western blotting,and immunofluorescence and measured the secreted TF with a commercial ELISA kit.Results No significant pathological injury was observed in the tissues of the control group.Mice treated with heat stress had various degrees of structural injuries and hemorrhagic and inflammatory changes in multiple tissues.Compared to control group,the expression of TF mRNA significantly increased in the kidney of heat stress-treated mice with 0 and 3 h recovery time(1.719±0.018,1.241±0.178 vs.1.000±0.063),the lung with 3 h recovery time(2.444±0.511 vs.1.000±0.106)and the liver with 6 h recovery time(7.312±0.618 vs.1.000±0.147)(P<0.05).The concentration of TF in plasma also sustainedly elevated in mice with 0,3,6,and 9 h recovery time after heat stress as compared to control group[(132.426±17.920)pg/ml,(119.400±10.267)pg/ml,(107.374±13.495)pg/ml,(163.767±22.810)pg/ml vs.(75.479±13.831)pg/ml,respectively,P<0.01].The expression levels of TF mRNA were higher in heat stress HUVECs with 6 h and 9 h recovery time than the control cells(1.905±0.354,2.564±0.297 vs.1.000±0.097,P<0.01).Secreted TF in the supernatant from HUVECs treated with heat stress and different recovery time also increased significantly[(36.309±4.101)pg/ml,(38.425±5.484)pg/ml,(41.655±4.380)pg/ml,(43.586±4.718)pg/ml vs.(14.996±0.254)pg/ml,P<0.01].Conclusion Heat stress increased early expression and secretion of TF in vascular endothelial cells.Vascular endothelial cells may be a main source of circulating TF in heat stroke.

Objective To investigate the effect of inhaled corticosteroids(ICS)on adverse outcomes in chronic obstructive pulmonary disease(COPD)(COPD-CAP)patients with community-acquired pneumonia(CAP).Methods The clinical data of COPD-CAP patients who visited the respiratory department of respiratory of Wenzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2021 to January 2023 was retrosspective collected.They were divided into an ICS group and a non ICS group based on whether they were eligible for ICS treatment.A univariate analysis was used to compare the differences in general data,imaging outcomes(multilobed infiltration and pleural effusion),and clinical outcomes(non-invasive mechanical ventilation,invasive mechanical ventilation,ICU admission,and 30-day mortality)between two groups.The Logistic regression was used to explore the relationship between ICS and imaging and clinical outcomes.Result A total of 120 COPD patients were included in this study,including 38 in the ICS group,62 in the non ICS group.The univariate results showed that COPD-CAP patients in the ICS group had lower GOLD scores,PSI scores,and CURB-65 scores(P＜0.05).The multivariate Logistic regression showed that the use of ICS reduces the risk of multi leaf infiltration[OR=0.291,95％CI(0.123,0.687),P=0.005],pleural effusion[OR=0.309,95％CI(0.105,0.908),P=0.033],non-invasive mechanical ventilation[OR=0.040,95％CI(0.012,0.129),P＜0.001],invasive mechanical ventilation[OR=0.099,95％CI(0.013,0.783),P=0.028],ICU occupancy[OR=0.207,95％CI(0.056,0.762),P=0.018],and 30-day mortality[OR=0.179,95％CI(0.039,0.822),P=0.027].Conclusion ICS reduces the risk of multilobed infiltration,pleural effusion,mechanical ventilation usage,ICU occupancy,and 30-day mortality in COPD patients admitted to CAP.

The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium unveiled numerous research advances which provide meaningful insights into the selection of treatment regimens of prostate cancer. Precision multi-treatment based on patients’ characteristics has become the predominant approach, including the use of a three-drug combination therapy for metastatic hormone-sensitive prostate cancer, and poly adenosine diphosphate ribose polymerase inhibitor therapy for metastatic castration-resistant prostate cancer. Nuclear medicine therapy and radiotherapy are also receiving significant attention. Integrated nuclear medicine diagnosis and therapy show immense potential for non-metastatic castration-resistant prostate cancer. Additionally, for localized prostate cancer, stereotactic body radiotherapy is a preferred alternative to surgery. This article sheds light on several key studies presented at the conference, focuses on prostate cancer treatment at different stages, and intends to enhance the therapeutic outcome for prostate cancer patients.