Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

Objective To observe the value of vector flow mapping(VFM)technique for assessing changes of left ventricular diastolic function in ovarian cancer(OC)patients who underwent postoperative chemotherapy.Methods Totally 37 OC patients who received postoperative chemotherapy were prospectively enrolled in chemotherapy group,while 40 healthy adults were taken as controls(control group).Routine echocardiography and VFM were performed for chemotherapy group before chemotherapy,after 3 and 6 cycles of chemotherapy,also for controls at enrollment,and comparison was performed between groups before chemotherapy,as well as among different time points within chemotherapy group,and the correlations of VFM results with hemoglobin and routine echocardiographic results in chemotherapy group were analyzed.Results No significant difference of age,body mass,body surface area(BSA),nor hemoglobin level,routine echocardiographic and VFM results before chemotherapy was found between groups(all P＞0.05).With the process of chemotherapy,hemoglobin level gradually decreased,the isovolumic relaxation period(IR),atrial systole period(AS)intraventricular pressure difference(IVPD)and intraventricular pressure gradient(IVPG)of the left ventricle gradually increased(adjusted P＜0.05),whereas routine echocardiography only showed that the left atrial volume index(LAVI)and the ratio of early mitral inflow velocity and the mean mitral annular early diastolic velocity(E/e')increased after 6 cycles of chemotherapy compared with those pre-chemotherapy(adjusted P＜0.05).In chemotherapy group,VFM results in all diastolic subphases were strongly correlated with hemoglobin levels(|r|=0.718 to 0.836,all P＜0.05),weakly to moderately correlated with LAVI(|r|=0.375 to 0.525,all P＜0.05)and moderately correlated with E/e'(|r|=0.424 to 0.537,all P＜0.05).Conclusion The diastolic function of left ventricle was probably damaged in early stage after postoperative chemotherapy in OC patients.VFM might detect slight changes of early diastolic function of left ventricle more sensitively than routine echocardiography.

Objective:To investigate the impact of the clinicopathological characteristics of anorectal malignant melanoma (ARMM) on the prognosis.Methods:The clinicopathological data of 40 ARMM patients undergoing surgery at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from Apr 2012 to Apr 2022 were collected, and the impact of different clinicopathological factors and treatment modalities on the overall survival of ARMM patients was investigated using Kaplan-Meier survival analysis and multifactorial Cox proportional risk model analysis.Results:Among 40 ARMM patients , 16 were male and 24 were female. The median age of onset was 61 yr. The median follow-up period for all patients was 47 (25-69) months, with a median survival of 19 (15-23) months and 1-year and 3-year survival rates of 74.3% and 21.7%, respectively. There was no statistically significant difference in survival time between the two groups of patients receiving wide local excision and abdominoperineal resection( χ2=1.281, P=0.258). Univariate analysis showed that overall survival in patients with ARMM was related to tumour diameter, depth of infiltration, specimen margin and lymph node metastasis ( χ2=1.281, P=0.039; χ2=3.760, P=0.042; χ2=6.581, P=0.010; χ2=21.683, P<0.001), and multivariate analysis suggested that lymph node metastasis was an independent risk factor for overall survival in patients with ARMM. Conclusion:Tumour diameter, depth of infiltration, specimen margin and lymph node metastasis were important prognostic influences in ARMM, and lymph node metastasis was an independent risk factor for overall survival in ARMM patients.

The death rate of colorectal cancer (CRC) is the fourth in worldwide. It is an important cause of cancer-related death and seriously affects the survival and quality of life of patients. Surgery, chemotherapy and radiotherapy are the main treatments for CRC. However, the overall survival of CRC patients has not been significantly improved. So the new treatments are urgently needed. Tumor immune escape plays a key role in tumor proliferation, recurrence and metastasis. Immune checkpoints programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) play an important role in tumor immune escape. Anti-PD-1/PD-L1 therapy has become a hotspot in cancer research. More and more studies have showed anti-PD-1/PD-L1 immunotherapy has achieved remarkable efficacy in the treatment of microsatellite instability-high (MSI-H) CRC. Therefore, this paper summarizes the clinical application of anti-PD-1/PD-L1 therapy in the treatment of CRC and the various strategies to improve its low response rate. And the predictive value of PD-L1 expression on the surface of tumor cells in the prognosis of CRC is also reviewed.

Objective:To explore the application value of a novel ultrasonic scale in the evaluation of sub-massive pulmonary embolism (sub-PE).Methods:Retrospective analyses were conducted in 137 patients with acute pulmonary embolism confirmed by computed tomography pulmonary angiography (CTPA) in the second affiliated hospital of Harbin Medical University from September 2017 to June 2019. They were divided into experimental set (77 cases) and testing set(60 cases). According to the European Society of Cardiology (ESC) guidelines for pulmonary embolism in 2019, the patients were classified into sub-PE(71 cases) and small pulmonary embolism(small-PE, 66 cases). Parameters in the experimental set were screened by statistical methods to make an ultrasonic scale, and then the patients in the testing set were scored by the scale. ROC curve was plotted to calculate the diagnostic efficacy of the ultrasonic scale for sub-PE.Results:①The patients of sub-PE were older than small-PE patients [(61.57±1.45) years vs (56.31±1.59) years, P=0.016], but there was no significant difference between the two groups in other general data( P>0.05). ②Within the 77 pulmonary embolism patients in the experimental set, 41(53.25%) were classified as the sub-PE and 36(46.75%) as the small-PE. Compared with the small-PE group, right ventricular diameter, pulmonary artery trunk diameter, right ventricle/left ventricle ratio, tricuspid regurgitation velocity, the Tei index and the inferior vena cava diameter in the sub-PE group increased significantly ( P<0.05), and right ventricular wall motion amplitude, right atrium area rate, right ventricular area rate, tricuspid annulus systolic displacement, collapse rate of inferior vena cava and pulmonary artery blood flow acceleration time decreased significantly ( P<0.05); ③Fifteen ultrasonic parameters were used in the ultrasonic scale. The scale in sub-PE group of the testing set was significantly increased compared with that in small-PE group (11.63±3.87 vs 4.43±1.96, P<0.001). ROC showed that the AUC in diagnosing sub-PE by ultrasonic scale was 0.96. When the cut-off value was 6.5, the sensitivity and specificity were 90.00% and 83.33%, respectively. Conclusions:The novel ultrasonic scale can provide a comprehensive and feasible ultrasound imaging method for evaluation of sub-PE.