Objective To investigate the mechanism and optimal concentration of anrotinib on ovarian clear cell carcinoma.Methods Ovarian clear cell carcinoma cells were cultured in vitro,by using renal clear cell carcinoma cells and renal papillary cell carcinoma cells as control cancer cells,and the effects of different concentrations of anlotinib(5,10,15,20μmol/L)on the proliferation,migration,and invasion capabilities of three cancer cell lines were investigated.Compared with the experimental results of renal clear cell carcinoma cells and renal papillary cell carcinoma cells,the advantages of anlotinib on ovarian clear cell carcinoma cells were investigated and advanced its position in clinical practice.Results Anlotinib at the concentrations of 5,10,15,and 20μmol/L can effectively inhibit the proliferation,migration,and invasion ability of ovarian clear cell carcinoma cells,renal clear cell carcinoma cells,and renal papillary cell carcinoma cells.Among them,the optimal action concentration of anlotinib on all three cancer cells fell in the range of 5-10 μmol/L.However,in the three cancer cells,anlotinib was more potent in ovarian clear cell carcinoma cells.Conclusion The effect of anlotinib on ovarian clear cell carcinoma cells has obvious advantages over renal clear cell carcinoma cells and renal papillary cell carcinoma cells,with the optimal concentration of 5-10 μmol/L.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

Objective To investigate the mechanism and optimal concentration of anrotinib on ovarian clear cell carcinoma.Methods Ovarian clear cell carcinoma cells were cultured in vitro,by using renal clear cell carcinoma cells and renal papillary cell carcinoma cells as control cancer cells,and the effects of different concentrations of anlotinib(5,10,15,20μmol/L)on the proliferation,migration,and invasion capabilities of three cancer cell lines were investigated.Compared with the experimental results of renal clear cell carcinoma cells and renal papillary cell carcinoma cells,the advantages of anlotinib on ovarian clear cell carcinoma cells were investigated and advanced its position in clinical practice.Results Anlotinib at the concentrations of 5,10,15,and 20μmol/L can effectively inhibit the proliferation,migration,and invasion ability of ovarian clear cell carcinoma cells,renal clear cell carcinoma cells,and renal papillary cell carcinoma cells.Among them,the optimal action concentration of anlotinib on all three cancer cells fell in the range of 5-10 μmol/L.However,in the three cancer cells,anlotinib was more potent in ovarian clear cell carcinoma cells.Conclusion The effect of anlotinib on ovarian clear cell carcinoma cells has obvious advantages over renal clear cell carcinoma cells and renal papillary cell carcinoma cells,with the optimal concentration of 5-10 μmol/L.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Objective:To evaluate the economy of recombinant human thrombopoietin(rhTPO)combined with conventional therapy compared with conventional therapy in the treatment of sepsis-associated thrombocytopenia(SIT)from the perspective of China's health service system.Methods:The decision tree model was constructed,and the minimum cost analysis and cost-effectiveness analysis were used to evaluate the economy based on the characteristics of sepsis.The economy was judged by two willingness to pay thresholds,and then the stability of the results was tested by sensitivity analysis.Results:rhTPO combined with conventional therapy can save 520.58 yuan for each 1％increase in survival rate compared with conventional therapy alone,which is an absolute advantage program.The single factor sensitivity analysis showed that the daily cost of ICU medical service and the duration of CRRT in the control group and the daily cost of ICU medical service in the experimental group had a great influence on the results,and the stability of the parameter outcome was good.The probability sensitivity analysis showed that when the willingness to pay threshold changes ranged 0～268 074 yuan,rhTPO has a 100％economical probability.Conclusion:Under the existing evidence,rhTPO combined with conventional treatment for SIT treatment is more economical on the basis of improving survival rate and equal safety.

The ataxia telangiectasia mutated(ATM)gene is an important tumor suppressor gene and a key effector gene in regulating the repair of double-strand DNA breaks.It plays an indispensable role in maintaining genetic stability,facilitating cell cycle arrest,and modulating cell apoptosis.When the ATM gene mutates,it fails to effectively induce the phosphorylation of downstream targets,leading to impaired DNA repair mechanisms,genetic instability,and chromosomal structural abnormalities,ultimately promoting abnormal proliferation of tumor cells.Analysis of next-generation sequencing(NGS)datas reveals a relatively high mutation rate of the ATM gene in bladder cancer cells.Relevant studies have shown that ATM gene regulates the proliferation,invasion,and metastasis of bladder cancer cells through the signaling pathways such as nuclear transcription factor-κB(NF-κB)and Interferon-γ(IFNγ).Mutanted ATM gene can enhance patients'sensitivity to radiotherapy and chemotherapy,and boost the efficacy of immunotherapy,resulting in a generally better prognosis for patients with ATM gene mutation.This finding marks ATM gene as a potential therapeutic target and predictive prognosis biomarker for bladder cancer patients.Therefore,this article will comprehensively review the research on the ATM gene in bladder cancer from 3 aspects:the structural characteristics of the ATM gene and its tumor-suppressing and tumor-promoting functions,the mechanism of action of the ATM gene in the occurrence and development of bladder cancer,and the impact of the ATM gene on the treatment and prognosis of bladder cancer patients.Additionally,the future research directions of the ATM gene was prospected,with the aim of providing new targets for the drug treatment of bladder cancer,and bringing new hope for the treatment of bladder cancer patients.

Ferroptosis is a form of iron dependent cell death,which is closely related to the progress and prognosis of bladder cancer(BCa).Among them,erroptosis related genes(FRGs)play an important role in the biological effects of BCa,such as participating in regulating the proliferation,migration,metastasis,drug resistance,immune regulation,and therapeutic efficacy of BCa cells.In addition,FRGs are also important biomarkers for predicting the prognosis of tumor patients.However,the specific mechanism of action of FRGs in BCa remains elusive.How to use FRGs to predict the prognosis of BCa and guide the treatment of BCa is still in the exploratory stage.Therefore,exploring the regulatory and predictive role of FRGs in BCa is particularly important for the diagnosis and treatment of BCa.This article aims to systematically elucidate the role of FRGs in the occurrence,development,treatment,and prognosis of BCa.To provide theoretical reference for further exploring the treatment of refractory and drug-resistant BCa patients,and constructing prognostic risk prediction models.

Objective:This study aimed to analyze cytomegalovirus (CMV) reactivation and its influencing factors in patients with B-lymphocyte malignancy who received chimeric antigen receptor T (CAR-T) cell therapy.Methods:This study retrospectively reviewed patients with B-lymphocyte malignancy who received CAR-T cell therapy in the First Affiliated Hospital of Soochow University from January 2021 to December 2023. The data of patients who underwent CMV-DNA detection and/or pathogen metagenomic sequencing twice or more within 100 days after CAR-T cell therapy were analyzed. The clinical characteristics of the CMV reactivation and non-activation groups were compared. The factors related to CMV reactivation were analyzed with the Chi-square test and nonparametric rank sum test, and the risk factors were examined with Logistic regression.Results:This study included 86 patients, among whom 18 (20.9%) had CMV reactivation, and the median time of reactivation was 20 (1-95) days. All of the 18 patients had CMV viremia, and no CMV disease was observed. Seven patients turned to the latent state after continuing acyclovir antiviral therapy, and 11 patients returned to the latent state after upgrading the antiviral therapy to first-line drugs, including ganciclovir and foscarnet sodium. Six or more courses of anti-tumor treatment before CAR-T cell therapy, allogeneic hematopoietic stem cell transplantation within 2 years before CAR-T cell therapy, non-remission before treatment, and the use of high-dose glucocorticoids and/or tocilizumab were related to CMV reactivation, among which allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and the use of high-dose glucocorticoids and/or tocilizumab treatment were independent risk factors for CMV reactivation.Conclusion:Patients with B-lymphocyte malignancy who received CAR-T cell therapy have the risk of CMV reactivation, especially for those who received allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and those who received high-dose glucocorticoids and/or tocilizumab treatment.

Objective:To assess the predictive value of dosiomics in predicting the occurrence of bone marrow suppression (BMS) in patients with pelvic tumors during radiotherapy.Methods:A retrospective analysis was conducted on the clinical data and radiotherapy planning documents of 129 patients with pelvic region tumors who underwent radiotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2019 to January 2023. The region of interest (ROI) was outlined for bone marrow in the pelvic region by Accu Contour software in planning CT, and the ROI was exported together with the dose distribution file. According to a stratified randomization grouping method, the patients were divided into the training set and test set in an 8 vs. 2 ratio. The dosiomic features were extracted from the ROI, and the two independent samples t-test and the least absolute shrinkage and selection operator (LASSO) algorithm was employed to identify the best predictive characteristics. Subsequently, the dosiomic scores were calculated. Clinical predictors were identified through both univariant and multivariate logistic regression analyses. Predictive models were constructed by using clinical predictors alone and combining clinical predictors and dosiomic scores. The efficacy of predictive model was assessed by plotting the receiver operating characteristic (ROC) curve and evaluating its performance through the area under the ROC curve (AUC), the calibration curve, and decision curve analysis (DCA). Results:Fourteen dosiomic features that showed a strong correlation with the occurrence of BMS were screened and utilized to calculate the dosiomic scores. Based on both univariant and multivariate logistic regression analyses, chemotherapy, planning target volume (PTV) and V 5 Gy were identified as clinical predictors. According to the combined model, the AUC values for the training set and test set were 0.911 and 0.868, surpassing those of the clinical model (AUC=0.878 and 0.824). Furthermore, the analysis of both the calibration curve and DCA suggested that the combined model had higher calibration and net clinical benefit. Conclusion:The combined model has a high diagnostic value for predicting BMS in patients with pelvic tumors during radiotherapy.