Application of predictive model based on CT radiomics and machine learning in diagnosis for occult locally advanced esophageal squamous cell carcinoma before treatment: A two-center study.

PURPOSE: Development and validation of a radiomics model for predicting occult locally advanced esophageal squamous cell carcinoma (LA-ESCC) on computed tomography (CT) radiomic features before implementation of treatment. METHODS: The study retrospectively collected 574 patients with esophageal squamous cell carcinoma (ESCC) from two medical centers, which were divided into three cohorts for training, internal and external validation. After delineating volume of interest (VOI), radiomics features were extracted and subjected to feature selection using three robust methods. Subsequently, 10 machine learning models were constructed, among which the optimal model was utilized to establish a radiomics signature. Furthermore, a predictive nomogram incorporating both clinical and radiomics signatures was developed. The performance of these models was evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis as well as measures including accuracy, sensitivity, and specificity. RESULTS: A total of 19 radiomics features were selected. The multilayer perceptron (MLP), which was found to be optimal, achieved an AUC of 0.919, 0.864 and 0.882 in the training, internal and external validation cohorts, respectively. Similarly, MLP showed good accuracy in distinguish occult LA-ESCC in subgroup of cT1-2N0M0 diagnosed by clinicians with 0.803 and 0.789 in two validation cohorts respectively. By incorporating the radiomics signature with clinical signature, a predictive nomogram demonstrated superior prediction performance with an AUC of 0.877 and accuracy of 0.85 in external validation cohort. CONCLUSION: The radiomics and machine learning model can offers improved accuracy in prediction of occult LA-ESCC, providing valuable assistance to clinicians when choosing treatment plans.

Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study.

Purpose: The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery. Methods: Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis. Results: A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016). Conclusion: In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.

ß-C-H Allylation of Trialkylamines with Allenes Promoted by Synergistic Borane/Palladium Catalysis.

Functionalization of the C(sp3 )-H bonds of trialkylamines is challenging, especially for reactions at positions other than the α position. Herein, we report a method for ß-C(sp3 )-H allylation of trialkylamines. In these reactions, which involve synergistic borane/palladium catalysis, an enamine intermediate is first generated from the amine via α,ß-dehydrogenation promoted by B(C6 F5 )3 and a base, and then the enamine undergoes palladium-catalyzed reaction with an allene to give the allylation product. Because the hydride and the proton resulting from the initial dehydrogenation are ultimately shuttled to the product by B(C6 F5 )3 and the palladium catalyst, respectively, these reactions show excellent atom economy. The establishment of this method paves the way for future studies of C-H functionalization of trialkylamines by means of synergistic borane/transition-metal catalysis.

C3-Cyanation of Pyridines: Constraints on Electrophiles and Determinants of Regioselectivity.

Methods for C-H cyanation of pyridines are rare. Here, we report a method for C3-selective cyanation of pyridines by a tandem process with the reaction of an in situ generated dihydropyridine with a cyano electrophile as the key step. The method is suitable for late-stage functionalization of pyridine drugs. The low reduction potential of the electrophile and effective transfer of the nitrile group were found to be essential for the success of this method. We studied the reaction mechanism in detail by means of control experiments and theoretical calculations and found that a combination of electronic and steric factors determined the regioselectivity of reactions involving C2-substituted pyridines.

[miR-129 in the diagnosis, treatment and prediction of clinical prognosis of prostate cancer].

OBJECTIVE: To explore the value of miR-129 in the diagnosis, treatment and prediction of the clinical prognosis of PCa by observing the correlation between miR-129 and the progression of the malignancy. METHODS: This retrospective analysis included 310 male patients who visited the Department of Urology of the General Hospital of Eastern Theater Command from January 2014 to January 2022, 80 as normal healthy men, 80 with BPH, and the other 150 with PCa treated by radical prostatectomy without chemotherapy, radiotherapy or androgen-deprivation therapy. We determined the miR-129 expression in the serum and prostatic tissue of all the subjects by real-time quantitative PCR (RT-qPCR), performed pathological grading of the primary cancerous and pericancerous (≥ 3 cm from the focus) prostate tissues from the 150 PCa patients, collected the demographic and clinical data on all the subjects, and analyzed the correlation of their demographic data with the clinical parameters. We selected and transfected PC-3 and DU-145 cell lines with miR-129 precursor or miR-129 scramble, assessed the proliferation ability of each cell line and detected the expression levels of related proteins by cell proliferation assay and Western blot. RESULTS: The expression of miR-129 was significantly decreased in the serum of the PCa patients compared with that in the normal healthy men and BPH patients (P < 0.01), so was it in the PCa tissue in comparison with that in the pericancerous prostatic tissue (P < 0.01), and it was negatively correlated with the preoperative serum PSA level (P < 0.001), histological grade (P < 0.001), pathological stage (P < 0.001), Gleason score (P < 0.001), lymph node metastasis (P = 0.02), angiolymphatic invasion (P = 0.021) and biochemical recurrence (BCR) (P=0.001). Kaplan-Meier analysis showed a strong correlation of down-regulated miR-129 expression with a lower BCR-free survival rate, while multivariate survival analysis indicated that the expression of miR-129 was an independent prognostic indicator of BCR-free survival of the PCa patients (P < 0.001). Highly expressed miR-129 significantly inhibited the proliferation of PCa cells by regulating the expressions of cell cycle-regulatory proteins. CONCLUSION: The expression of miR-129 is significantly down-regulated in PCa tissues, which plays an important role in inhibiting the proliferation of PCa cells and tumor progression and improving BCR-free survival. Therefore, miR-129 can be considered as a new independent biomarker for the diagnosis, treatment and prediction of the clinical prognosis of PCa.