Colorectal cancer （CRC） is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients， problems such as low quality of life， obvious side effects， and unsatisfactory clinical efficacy still exist， which cannot fully satisfy the overall needs of patients. For this reason， it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years， with the deepening of research， ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells， overcome tumor drug resistance， enhance anti-tumor efficacy， and prevent tumor progression and recurrence. Therefore， regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine （TCM） has been widely used in CRC treatment due to its advantages of multiple components， multiple targets， low drug resistance， and few side effects， and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways， such as iron metabolism， lipid metabolism， the cystine/glutamate antiporter system X_c^- （System X_c^-）/glutathione （GSH）/glutathione peroxidase 4 （GPX4）， ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀）/nicotinamide adenine dinucleotide phosphate ［NAD（P）H］， tumor protein 53 （p53）， nuclear factor erythroid-2-related factor 2 （Nrf2）， and non-coding RNA pathways to inhibit the growth and proliferation of CRC， thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC， therapeutic targets and prognosis-related markers associated with ferroptosis in CRC， and research progress on TCM targeting and regulating ferroptosis for CRC intervention， aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.

Colorectal cancer （CRC） is a common malignant tumor of the digestive tract with high morbidity and mortality. Although existing treatments can prolong the survival of patients， problems such as low quality of life， obvious side effects， and unsatisfactory clinical efficacy still exist， which cannot fully satisfy the overall needs of patients. For this reason， it is crucial to explore the mechanism underlying the development of CRC and to identify new treatment strategies. In recent years， with the deepening of research， ferroptosis has been gradually proven to effectively inhibit the proliferation and metastasis of CRC cells， overcome tumor drug resistance， enhance anti-tumor efficacy， and prevent tumor progression and recurrence. Therefore， regulating ferroptosis is expected to become a new strategy for the treatment of CRC. Traditional Chinese medicine （TCM） has been widely used in CRC treatment due to its advantages of multiple components， multiple targets， low drug resistance， and few side effects， and has gradually become a current research hotspot. Extensive studies have shown that TCM active ingredients and compound formulae can regulate ferroptosis-related pathways， such as iron metabolism， lipid metabolism， the cystine/glutamate antiporter system X_c^- （System X_c^-）/glutathione （GSH）/glutathione peroxidase 4 （GPX4）， ferroptosis suppressor protein 1 （FSP1）/coenzyme Q₁₀ （CoQ₁₀）/nicotinamide adenine dinucleotide phosphate ［NAD（P）H］， tumor protein 53 （p53）， nuclear factor erythroid-2-related factor 2 （Nrf2）， and non-coding RNA pathways to inhibit the growth and proliferation of CRC， thereby exerting anti-tumor effects. This review systematically summarized the mechanisms of ferroptosis related to CRC， therapeutic targets and prognosis-related markers associated with ferroptosis in CRC， and research progress on TCM targeting and regulating ferroptosis for CRC intervention， aiming to provide new perspectives and a theoretical basis for the prevention and treatment of CRC with TCM.

Objective To investigate the effectiveness and safety of volumetric modulated arc therapy (VMAT) hypofractionated radiotherapy and intensity modulated conformal radiotherapy technique (IMRT) conventional fractionated radiotherapy after breast cancer radical operation.Methods Eighty-five patients with breast cancer modified radical operation admitted and treated in this hospital from March 1,2021 to De-cember 30,2021 were selected as the research subjects and divided into the VMAT group (n=41) and the IM-RT group (n=42) according to the random number table method.The VMAT group adopted the hypofrac-tionated radiotherapy,with the single fractionated dose of 2.9 Gy/frequency and radiotherapeutic total dose of 43.5 Gy/15 frequencies;the IMRT group adopted the IMRT conventional fractionated radiotherapy,with the single fractionated dose of 2.0 Gy/frequency and radiotherapeutic total dose of 50.0 Gy/25 frequencies.The planning target region V95,V110,conformity index,homogeneity index,treatment time,V5,V20,V30,average dose (Dmean) in the affected side lung,humeral head Dmean and heart V30,Dmean were compared between the two groups.Meanwhile,local recurrence,distant metastasis,disease-free survival and acute and chronic radiation injury were compared between the two groups.Results Compared with the IMRT group,V95 in the VMAT was higher,V110 and homogeneity index were lower,the treatment time was shorter,V5 in the affected lung,Dmean and Dmean in the affected humeral head were lower,V30 in the affected lung was higher,heart V30 in the left side breast cancer was lower,heart Dmean in the right side breast cancer was lower,and the differences were statistically significant (P<0.05).All patients survived without local relapse.The distant metastasis rate and disease free survival rate had no statistical difference between the two groups (P>0.05).Follow up lasted for 12 months,the incidence rates of grade Ⅰ-Ⅱ acute radiodermatitis,radiation esophagitis,chronic radioder-matitis and radiation pneumonia had no statistical differences between the two groups (P>0.05).The inci-dence rate of grade Ⅰ-Ⅱ shoulder dysfunction in the VMAT group was lower than that in the IMRT group with statistical difference (P<0.05).No grade Ⅱ and above acute and chronic radiation injury in the two groups occurred.Conclusion VMAT hypofractionated radiotherapy after breast cancer radical operation is safe and effective.

Objective To calculate the pre-stretching of the microscopic components of the aortic wall under physiological homeostasis by considering a three-dimensional(3D)residual stress field.Methods The aortic wall was simplified into a double-layer ideal circular tube,and the 3D residual stress field of the vascular wall was calculated based on a 3D expansion angle experiment.Then,the in vivo stress distribution characteristics under mean blood pressure and the pre-stretching of each microscopic constituent of the vascular wall under a physiologically steady state were obtained.The inverse problem was constructed according to the internal pressure-radius relationship measured in vivo.Physiological homeostasis of the aorta was considered the reference state,and inversion identification of the material parameters of the aorta in vivo was realized while integrating the three residual stress fields.Results When residual stress was not considered,the mean stress of the middle membrane was greater than that of the outer membrane.When residual stress was considered,the outer membrane bore more stress than the middle membrane,and the outer membrane protected the middle membrane.The pre-stretching of the middle film with residual stress was lower than that without residual stress,whereas the pre-stretching of the outer film was higher than that without residual stress.Moreover,the pre-stretching of the outer membrane collagen fibers was greater than that of the middle membrane collagen fibers.The in vivo calculations of the material parameters of the aorta were performed using physiological homeostasis as the reference configuration,and the proportion of each component was consistent with the experimental results.However,the proportion of elastin in the outer membrane was significantly overestimated when the non-stress configuration was used as the initial configuration,which was inconsistent with the experimental results.Conclusions Residual stress significantly influences the pre-stretching and physiologically steady mechanical states of the microscopic components of the aortic wall.Therefore,it is necessary to fully consider the influence of residual stress to establish the physiologically steady state of the aortic wall accurately.Furthermore,it is also necessary to fully consider the 3D characteristics and layer specificity of residual stress in the in vivo identification of material parameters.

Multidrug resistance (MDR) is the main factor of tumor recurrence and chemotherapy failure in clinical practice. Its mechanism is relatively complex, and one of the most thoroughly studied mechanism is the overexpression of P-glycoprotein (P-gp) on tumor cell membrane. Most of the chemotherapy drugs are p-gp substrates, and tumor cells will transport the chemotherapy drugs to the extracellular through p-gp mediated active transport, so that the concentration of effective drugs in the cell is reduced, resulting in drug resistance, leading to the decline of clinical efficacy. The reversal agent of P-gp can reduce the intracellular pumping of chemotherapeutic drugs by regulating the expression and transport activity of P-gp, and enhance the sensitivity of tumor cells to chemotherapeutic drugs, thus improving the therapeutic effect. In this paper, we will summarize the natural plant active ingredients that can reverse P-gp mediated MDR to provide reference for clinical and related studies.

Objective:To establish a model C-GALAD for detecting hepatocellular carcinoma (HCC) from the chronic liver disease and healthy people based on the serum markers.Methods:A clinical cohort including 229 hepatocellular carcinoma patients, 2 317 patients with chronic liver disease and 982 healthy people, was retrospectively collected from eight hospitals or physical examination institutions from April 2018 to October 2020. The data were divided into a training set and a testing set by stratified sampling with a 6∶4 ratio. A predictive model was established on the training set using a logistic backward regression method and validated on the testing set. In addition, clinical data from March to July 2021 in Beijing You′ an Hospital affiliated to Capital Medical University, including 84 patients with liver cancer and 204 patients with chronic liver disease collected were used for external independent validation of the model. The receiver operating characteristic curve (ROC) area under curve (AUC), the sensitivity and the specificity were used to evaluate the effectiveness of the model.Results:Through the logistic backward regression method, the seven signatures including age, gender, alpha-fetoprotein (AFP), alpha-fetoprotein alloplasm-3 ratio (AFP-L3%), des-gamma-carboxyprothrombin(DCP), platelet (PLT) and total bilirubin (TBIL) were selected as risk factors in the detection model. The area under the ROC curve (AUC) of the model on the testing set was 0.954, with an 88.04% sensitivity and a 94.85% specificity, and the AUC of model on the external independent validation set was 0.943, with an 89.29% sensitivity and a 90.2% specificity, which were better than other published models.Conclusion:The C-GALAD Ⅱ model can accurately predict the risk of hepatocellular carcinoma occurrence, and thus provide a trustworthy diagnosis method of hepatocellular carcinoma.

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthetic pathway of polyamines and catalyzes the decarboxylation of ornithine to produce putrescine. Inhibition of ODC activity is a potential approach for the prevention and treatment of many diseases including cancer, as the expression levels and the activities of ODC in many abnormal cells and tumor cells are generally higher than those of normal cells. The discovery and evaluation of ODC inhibitors rely on the monitoring of the reaction processes catalyzed by ODC. There are several commonly used methods for analyzing the activity of ODC, such as measuring the yield of putrescine by high performance liquid chromatography, or quantifying the yield of isotope labelled carbon dioxide. However, the cumbersome operation and cost of these assays, as well as the difficulty to achieve high-throughput and real-time detection, hampered their applications. In this work, we optimized a real-time label-free method for analyzing the activity of ODC based on the macromolecule cucurbit[6]uril (CB6) and a fluorescent dye, DSMI (trans-4-[4-(dimethylamino) styryl]-1-methylpyridinium iodide). Finally, the optimized method was used to determine the activities of different ODC inhibitors with different inhibition mechanisms.
Bridged-Ring Compounds ; Imidazoles ; Ornithine ; Ornithine Decarboxylase ; Ornithine Decarboxylase Inhibitors ; Putrescine

Objective:To explore the efficacy and safety of urethroplasty combining the reconstruction of urethral plate with the enlargement of urethral cavity in the treatment of short penile urethral atresia or severe stricture.Methods:From January 2017 to September 2020, 10 patients, 22 to 78 years old and the average age 48, with short penile urethral atresia or severe stricture were treated in the Department of Urology, Henan University People’s Hospital, Henan Provincial People’s Hospital. The lengths of the stenotic or atresic segment were 0.2-0.5 cm, with an average length of 0.3 cm. They were all treated with one-stage urethroplasty to reconstructe urethral plate and enlarge urethral cavity with free prepuce skin grafts or pedicled flaps adjacent to the stenosis. By the guidance of urethral dilator, the strictured urethra was incised longitudinally on the ventral side of penis to the distance of 0.5 cm into the normal urethral mucosa at both ends. The stricture or atresic scar tissue of the urethra was removed. The distal and proximal corpus spongiosum were appropriately dissociated, and the urethral mucosa at the both ends of the dorsal side was anastomosed intermittently to reconstruct the urethral plate. Free prepuce skin grafts were used in 4 cases, and pedicled flaps adjacent to the stenosis were used in 6 cases to enlarge the urethral cavity.Results:In this study, the operation time ranged from 75 minutes to 100 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 ml to 65 ml, with an average of 45.5 ml. Followed up from 3 months to 3 years postopreatively, all of them did not have painful erection and penile curvature during erection, and felt the same as before in sexual life. Urinary flow rates were significantly improved in 9 cases, and the maximum flow rate was more than 15 ml/s. One recurred patient was cured after urethral dilatation.Conclusions:The one-stage urethroplasty combined the reconstruction of urethral plate with the enlargement of urethral cavity. The urethral plate was reconstructed through urethral resection of narrow segment and the urethral cavity was enlarged with free skin or pedicled flap. This technique has the advantages of a simple and safe operation with a high success rate and a less complication rate. It is an effective procedure to repair short penile urethral atresia or severe stricture.

Objective:To explore the efficacy and safety of urethroplasty combining the reconstruction of urethral plate with the enlargement of urethral cavity in the treatment of short penile urethral atresia or severe stricture.Methods:From January 2017 to September 2020, 10 patients, 22 to 78 years old and the average age 48, with short penile urethral atresia or severe stricture were treated in the Department of Urology, Henan University People’s Hospital, Henan Provincial People’s Hospital. The lengths of the stenotic or atresic segment were 0.2-0.5 cm, with an average length of 0.3 cm. They were all treated with one-stage urethroplasty to reconstructe urethral plate and enlarge urethral cavity with free prepuce skin grafts or pedicled flaps adjacent to the stenosis. By the guidance of urethral dilator, the strictured urethra was incised longitudinally on the ventral side of penis to the distance of 0.5 cm into the normal urethral mucosa at both ends. The stricture or atresic scar tissue of the urethra was removed. The distal and proximal corpus spongiosum were appropriately dissociated, and the urethral mucosa at the both ends of the dorsal side was anastomosed intermittently to reconstruct the urethral plate. Free prepuce skin grafts were used in 4 cases, and pedicled flaps adjacent to the stenosis were used in 6 cases to enlarge the urethral cavity.Results:In this study, the operation time ranged from 75 minutes to 100 minutes, with an average of 85.6 minutes. Intraoperative blood loss ranged from 20 ml to 65 ml, with an average of 45.5 ml. Followed up from 3 months to 3 years postopreatively, all of them did not have painful erection and penile curvature during erection, and felt the same as before in sexual life. Urinary flow rates were significantly improved in 9 cases, and the maximum flow rate was more than 15 ml/s. One recurred patient was cured after urethral dilatation.Conclusions:The one-stage urethroplasty combined the reconstruction of urethral plate with the enlargement of urethral cavity. The urethral plate was reconstructed through urethral resection of narrow segment and the urethral cavity was enlarged with free skin or pedicled flap. This technique has the advantages of a simple and safe operation with a high success rate and a less complication rate. It is an effective procedure to repair short penile urethral atresia or severe stricture.

Objective To simulate the interaction between the stent graft (SG) and the aortic wall with finite element (FE) analysis by considering the influence of residual stress field, so as to study the stent influence on stress distributions of the aortic wall. Methods The three-dimensional (3D) residual stress field was generated in an idealized bi-layered thick-wall aortic model via a stress-driven anisotropic growth model by reducing the transmural stress gradient. Upon virtually deploying the SG, the stress on the aortic wall was calculated. Results The 3D residual stress field, corresponding to an opening angle of 117.5°, was shown to reduce the transmural stress gradient in both the circumferential and axial directions. The maximum stress was found at the contact area between aortic wall and wave peak of the stent. At 20% oversize ratio of the stent, the maximum stresses on the aortic wall in circumferential and axial direction were 412 and 132 kPa, respectively, while the in-plane shear stresses σrθ and σrz were both 78 kPa. Under residual stress, the maximum radial, circumferential and axial stresses were decreased by 14.9%, 40.5% and 33.8%, respectively, while the maximum shear stresses σrθ ，σrz，σθz were reduced by 2.5%, 7.1% and 27%, respectively. With the increase of oversize ratio from 10% to 20%, the maximum radial, circumferential and axial stresses were increased by 316%, 129% and 41%, respectively, while the maximum shear stresses σrθ ，σrz，σθz were increased by 661%, 450% and 466%, respectively. Conclusions The residual stress can effectively reduce the transmural stress gradient. Both the residual stress and the oversize ratio of the stent play an important role in modulating the wall stress distribution and the maximum stress.