Objective To investigate the effect of ribonucleotide reductase regulatory subunit M2 （RRM2） on the malignant biological behavior and aerobic glycolysis of gastric cancer cells by regulating cyclin-dependent kinase （CDK） 1. Methods Human gastric cancer MKN-45 cells were divided into si-NC group （transfected with blank fragment）， CoCl₂+si-NC group （hypoxia control transfected with blank fragment）， CoCl₂+si-RRM2 group （hypoxia with RRM2 silencing）， CoCl₂+si-RRM2+pcDNA3.1 NC group （hypoxia with RRM2 silencing and blank vector） and CoCl₂+si-RRM2+pcDNA3.1 CDK1 group （hypoxia with RRM2 silencing and CDK1 overexpression）. The mRNA relative expression levels of RRM2 and CDK1 were analyzed by real time fluorescent quantitative reverse transcription PCR. Co-immunoprecipitation （CoIP） was used to analyze the interaction between RRM2 and CDK1 protein. MTT assay was used to analyze the proliferation activity of cells. The cell migration distance was detected by cell scratch assay. Cell apoptosis was detected by flow cytometry. Adenosine triphosphate （ATP） and glucose kit were used to detect ATP production and glucose consumption. The protein expressions of ENO1， RRM2， HK2， PKM2， GLUT1 and p-CDK1/CDK1 were detected by Western blotting. Results Real time fluorescent quantitative reverse transcription PCR results showed that the relative expression levels of CDK1 mRNA in si-NC group， CoCl₂+si-NC group and CoCl₂+si-RRM2 group were 1.01±0.15， 1.30±0.06 and 0.51±0.18， and the relative expression levels of RRM2 mRNA were 1.03±0.32， 1.59±0.28 and 0.44±0.17， respectively， and there were statistically significant differences （F=25.52， P=0.001； F=14.47， P=0.005）. The mRNA expressions of RRM2 and CDK1 in CoCl₂+si-NC group were higher than those in si-NC group. Compared with the si-NC group and the CoCl₂+si-NC group， the mRNA expressions of RRM2 and CDK1 were lower in the CoCl₂+si-RRM2 group （all P<0.05）. CoIP results showed that there was interaction between RRM2 and CDK1. MTT assay， cell scratch assay and flow cytometry showed that the cell proliferation activity of si-NC group， CoCl₂+si-NC group， CoCl₂+si-RRM2 group， CoCl₂+si-RRM2+pcDNA3.1 NC group and CoCl₂+si-RRM2+pcDNA3.1 CDK1 group were 1.04±0.01， 1.18±0.04， 0.84±0.03， 0.81±0.03 and 0.93±0.05， respectively. The cell migration distances were （301.83±2.75）， （369.67±0.76）， （176.50±6.38）， （175.83±3.69）， （254.17±1.61） μm， respectively. The apoptosis rates were 8.05%±0.21%， 5.75%± 0.20%， 28.28%±0.04%， 30.18%±1.51% and 17.79%±0.22%， respectively， all with statistically significant differences （F=73.82， P<0.001； F=1 600.01， P<0.001； F=787.15， P<0.001）. Compared with the si-NC group and CoCl₂+si-NC group， the proliferation and migration ability of cells in the CoCl₂+si-RRM2 group， CoCl₂+si-RRM2+pcDNA3.1 NC group and CoCl₂+si-RRM2+pcDNA3.1 CDK1 group were weaker， and the apoptosis rates were higher （all P<0.05）. Compared with the CoCl₂+si-RRM2+pcDNA3.1 NC group， the proliferation and migration ability of cells in the CoCl₂+si-RRM2+pcDNA3.1 CDK1 group were stronger， and the apoptosis rate was lower （all P<0.05）. The results of ATP and glucose detection showed that there were statistically significant differences in the amount of ATP production and glucose consumption among the above five groups （F=12.53， P<0.001； F=19.21， P<0.001）. Compared with the si-NC group， the glucose consumption of cells was lower in the CoCl₂+si-RRM2+pcDNA3.1 CDK1 group （P<0.05）. Compared with the CoCl₂+si-NC group， the ATP production and glucose consumption of cells in the CoCl₂+si-RRM2+pcDNA3.1 CDK1 group were lower （both P<0.05）. Compared with the CoCl₂+si-RRM2+pcDNA3.1 NC group， the ATP production and glucose consumption of the CoCl₂+si-RRM2+pcDNA3.1 CDK1 group were higher （both P<0.05）. Western blotting showed that there were statistically significant differences in the protein expressions of ENO1， RRM2， HK2， PKM2， GLUT1， and p-CDK1/CDK1 among the above five groups （all P<0.001）. Compared with the si-NC group and the CoCl₂+si-NC group， the protein expressions of ENO1， RRM2， HK2， PKM2， GLUT1 and p-CDK1/CDK1 in the CoCl₂+si-RRM2+pcDNA3.1 CDK1 group were lower （all P<0.05）. Compared with the CoCl₂+si-RRM2+pcDNA3.1 NC group， the protein expressions of ENO1， RRM2， PKM2， GLUT1 and p-CDK1/CDK1 in the CoCl₂+si-RRM2+pcDNA3.1 CDK1 group were higher （all P<0.05）. Conclusions Silencing RRM2 can inhibit the malignant biological behavior of gastric cancer cells and the occurrence of aerobic glycolysis by regulating CDK1.

Objective To construct a predictive model of ≥ grade 2 radiation esophagitis （RE） in patients with esophageal cancer during concurrent radiochemotherapy （CRT） based on machine learning （ML） algorithm. Methods A retrospective analysis was conducted on the clinical data of 276 patients with esophageal cancer who had received CRT at Lu'an Hospital of Anhui Medical University from January 2018 to January 2023. The occurrence of RE was evaluated according to grading criteria of RE developed by American Radiation Therapy Oncology Group， with ≥ grade 2 RE as the outcome event. After screening variables through the least absolute shrinkage and selection operator （LASSO） regression， the dataset was re-established. The dataset was then divided into training set （n=193） and testing set （n=83） in a 7∶3 ratio and included in four ML models： random forest （RF）， decision tree （DT）， extreme gradient boosting （XGBoost）， and support vector machine （SVM）. In the models， data training and model optimization were conducted in the training set， and model performance was evaluated in the testing set using the receiver operator characteristic （ROC） curve. The area under the curve （AUC）， accuracy， precision， sensitivity， and F1 score were calculated to assess the model. SHAP analysis was used to explain the optimal model. Results By the end of follow-up， 91 cases （32.97%） of esophageal cancer patients had experienced ≥ grade 2 RE during CRT. There were statistically significant differences in tumor lesion length （Z=-5.53， P<0.001）， Karnofsky performance status （KPS） score （χ²=5.92， P=0.015）， the Eastern Cooperative Oncology Group （ECOG） score （χ²=4.01， P=0.045）， hypertension （χ²=15.35， P<0.001）， diabetes （χ²=13.06， P<0.001）， white blood cell count （Z=-6.59， P<0.001）， neutrophil count （Z=-6.72， P<0.001）， and radiotherapy dose （χ²=9.81， P=0.002） between ≥ grade 2 RE occurrence group （n=91） and no occurrence group （n=185）. After LASSO regression screening， 7 characteristic variables were ultimately selected， which were tumor lesion length， ECOG score， KPS score， neutrophil count， hypertension， diabetes， and radiotherapy dose. ROC curve analysis showed that the XGBoost model had better predictive performance， with an AUC of 0.90， accuracy of 0.82， precision of 0.80， sensitivity of 0.73， and F1 score of 0.76. The AUC， accuracy， precision， sensitivity， and F1 score of RF model were 0.89， 0.78， 0.76， 0.48， and 0.59， respectively. The AUC， accuracy， precision， sensitivity， and F1 score of DT model were 0.72， 0.72， 0.44， 0.60， and 0.52， respectively. The AUC of SVM model was 0.74， with an accuracy of 0.82， precision of 0.52， sensitivity of 0.88， and F1 score of 0.65. The XGBoost model was explained using SHAP analysis， which indicated that the tumor lesion length， neutrophil count， hypertension， diabetes， and radiotherapy dose had a strong predictive ability for the occurrence of ≥ grade 2 RE during CRT in esophageal cancer patients. Conclusions The model established based on the XGBoost method has good predictive performance for the occurrence of ≥ grade 2 RE in esophageal cancer patients during CRT. Meanwhile， combined with SHAP analysis， it can provide an intuitive understanding of the impact of important features in the model on the outcome.

Objective To investigate the predictive value of maximum tumor diameter and the peripheral blood neutrophil to lymphocyte ratio （NLR） before radiotherapy for the occurrence of esophageal fistula after radiotherapy in patients with esophageal squamous cell carcinoma （ESCC）. Methods A total of 98 patients with ESCC who underwent radiotherapy in Hefei Cancer Hospital， Chinese Academy of Sciences from February 2017 to February 2021 were selected， and the patients were divided into esophageal fistula group （13 cases） and no esophageal fistula group （85 cases） according to whether esophageal fistula occurred during the follow-up process. The prognostic nutritional index （PNI）， NLR， and systemic inflammatory response index （SIRI） were calculated. Univariate and multivariate logistic regression were used to analyze the influencing factors of esophageal fistula， and the predictive value of each indicator was evaluated by using the receiver operator characteristic （ROC） curve. Results There were no statistically significant differences in age， smoking history， diabetes mellitus history， gender， concurrent chemotherapy and alcohol history between the esophageal fistula group and the no esophageal fistula group （all P>0.05）， while there were statistically significant differences in PNI （t=2.24， P=0.041）， NLR （t=3.75， P=0.001）， SIRI （t=2.68， P=0.015）. Univariate analysis showed that tumor length （OR=1.16， 95%CI： 1.01-1.35， P=0.043）， maximum tumor diameter （OR=1.63， 95%CI： 1.11-2.39， P=0.012）， PNI （OR=0.83， 95%CI： 0.71-0.98， P=0.023）， NLR （OR=1.94， 95%CI： 1.20-3.12， P=0.007） and SIRI （OR=1.82， 95%CI： 1.03-3.24， P=0.041） were related to esophageal fistula. Multivariate analysis showed that maximum tumor diameter （OR=2.17， 95%CI： 1.02-4.94， P=0.033） and NLR （OR=2.40， 95%CI： 1.89-6.59， P=0.018） were independent influencing factors for the development of esophageal fistula in patients with ESCC after radiotherapy. ROC curve analysis showed that the area under the curve of maximum tumor diameter before radiotherapy combined with NLR for predicting esophageal fistula in patients with esophageal squamous cell carcinoma after radiotherapy was 0.83 （95%CI： 0.74-0.90）， which was greater than that of maximum tumor diameter before radiotherapy （0.71， 95%CI： 0.63-0.81， Z=1.80， P=0.039） and NLR （0.74， 95%CI： 0.67-0.85， Z=1.64， P=0.046） alone. Conclusions The maximum tumor diameter before radiotherapy and NLR are closely related to the occurrence of esophageal fistula in ESCC after radiotherapy， and these factors are expected to serve as key predictors of the occurrence of esophageal fistula.

Although patients with stage pT_2-3N₀M₀ thoracic esophageal squamous cell carcinoma are staged earlier， their postoperative local recurrence and distant metastasis rates are higher， resulting in a low five-year survival rate of such patients. The current neoadjuvant treatment for such patients is still in the research stage， and whether to give adjuvant radiotherapy and chemotherapy after surgery is still controversial. In addition， the prognostic factors of patients with pT_2-3N₀M₀ thoracic esophageal squamous cell carcinoma have not yet been clarified， and the causes of recurrence and metastasis are not yet clear. Therefore， it is of great significance to clarify treatment strategies and explore the impact of prognostic factors on improving the survival rate of such patients， which is expected to provide new directions for improving the prognosis and survival rate of patients with pT_2-3N₀M₀ thoracic esophageal squamous cell carcinoma.

Esophageal cancer is one of the leading causes of death from cancer worldwide. Radiotherapy plays an important role in the treatment of esophageal cancer. Compared with photon radiotherapy， proton radiotherapy significantly reduces normal organ dose due to its unique biophysical properties， which makes this modality potential ideal for esophageal cancer treatment. Proton radiotherapy plays an important role in radical radiotherapy， neoadjuvant radiotherapy and re-radiotherapy for esophageal cancer. The efficacy is equivalent to or better than that of photon radiotherapy， and proton radiotherapy is superior than photon radiotherapy in security. The combination of proton radiotherapy and immunotherapy， the increase of radiotherapy dose， and large-scale randomized controlled studies based on intensity-modulated proton radiotherapy technology will be hot topics for further research.

The early diagnosis rate of esophageal cancer is low， and most of the patients are already in the middle or late stage when diagnosed， making treatment difficult， shortening the survival period and resulting in an extremely poor prognosis. In recent years， the continuous development of targeted therapy and immunotherapy has significantly improved the survival rate and therapeutic effect of esophageal cancer patients. Analyzing the research progress of targeted therapy and immunotherapy for esophageal cancer is of great significance and can provide reference for guiding the treatment of esophageal cancer.

In recent years， studies have found that the abnormal expression of rhythm genes is closely related to the risk of occurrence and the progression of the disease course of colorectal cancer. In addition， chronotherapy based on the circadian rhythm theory has shown certain effects in the clinical treatment of colorectal cancer， but there are still great limitations. Therefore， it is very important to clarify the mechanism of action of rhythm genes in the occurrence and development of colorectal cancer， which may provide a theoretical basis for the clinical application of chronotherapy.