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.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

Objective To evaluate the effect of prophylactic intra-aortic balloon pump (IABP) on reduction of the incidence of major adverse cardiovascular events (MACE) occurred during perioperativeperiod.Methods A total of 246 high-risk patients with AMI admitted from October 2013 through October 2016 were divided into two groups:prophylactic IABP group (n =144) and remedial IABP group (n =102).The likely complications associated with IABP were observed such as dissecting aneurysm,thrombocytopenia,lower extremity thrombosis,anemia,hematoma at puncture site.The comparison of postoperative heart failure,cardiogenic shock and refractory arrhythmia,and nosocomial death between two groups was carried out.The difference in length of time for treatment with IABP between two groups was compared.Statistical analysis of measurement data expressed in (x) ± s using independent sample t test.Countdata expressed in percentage were compared with chi-square test.Non-normal distribution data were checked with median ± interquartile range.P ＜ 0.05 for the difference was concerned statistically significant.Results Gensini score was higher in prophylactic IABP group (t =2.311,P ＜ 0.05).In remedial IABP group,the operative time was longer (t =2.626,P ＜ 0.05),the higher rate of using therapeutic medicine was significant (x2 =60.105,P ＜0.01),the no reflow rate was higher (x2 =19.920,P ＜0.01),the amount of contrast agent used was greater (t =2.437,P ＜ 0.05),the in-hospital incidence of heart failure was higher (x2 =31.638,P ＜ 0.01),the rate of nosocomial postoperative cardiogenic shock was higher (x2 =7.793,P ＜0.01),and the number of in-hospital death increased (x2 =4.827,P ＜ 0.05).Compared with prophylactic IABP group,higher BNP (t =7.44 7,P ＜ 0.05),and lower LVEF (t =3.557,P ＜ 0.05)were found in remedial IABP group.Conculsion Prophylactic employment of IABP for the treatment of high-risk AMI patients effectively improved the survival rate and reduced peri-opearative MACE.

Objective To evaluate the feasibility and therapeutic efficacy of prophylactic implantation of intraaortic balloon pump in patients with high-risk coronary artery disease.Methods 121 patients with high-risk coronary heart disease who received prophylactic implantation of intraaortic balloon pump in percutaneous coronary intervention were enrolled as the treatment group (Group A),and another 119 patients with high-risk coronary heart disease who had conventional coronary intervention were enrolled as the control group (Group B).The rates of intraoperative malignant arrhythmia (ventricular tachycardia,ventricular fibrillation),acute left heart failure,cardiogenic shock and sudden death were compared between the two group.NT-proBNP levels,left ventricular systolic function and the rates of major adverse cardiac events,within 30 days of PCI and after 1 year were compared between the two groups.Results The event rates of intraoperative malignant arrhythmia,acute left heart failure,cardiogenic shock,and sudden death in Group A was significantly lower than those in Group B (all P ＜ 0.05).Postoperative hematoma were found in 2 cases,aortic dissection in 1 case and thrombocytopenia in 1 case in Group A without significant difference as compared to Group B (P ＞ 0.05).Within 30 days after PCI,NT-proBNP levels and left ventricular diastolic diameter in Group A were lower than those in Group B while the left ventricular ejection fraction in Group A was higher than that in Group B (all P ＜ 0.05).The rates of major cardiac adverse events,including sudden cardiac death and severe heart failure were lower than those in Group B (all P ＜ 0.05).At 1 year after PCI,the NT-proBNP levels left ventricular diastolic diameter in Group A were lower than those in Group B with the left ventricular ejection fraction in Group A was higher than that in Group B (all P ＜ 0.05).There were no significant differences in the rates of major cardiac adverse events,including sudden cardiac death and severe heart failure after 1 year(all P ＞ 0.05).Conclusions For patients with high-risk coronary heart disease undergoing coronary intervention,prophylactic implantation of intraaortic balloon pump may decrease the incidence of intraoperative complications,reduce the incidence of cardiac death and severe heart failure within 30 days,and improve the left ventricular function after 1 year.Its role in reducing long term major cardiac adverse events after 1 year still needs more clinical trials for funther justification.

Objective To investigate the epidemiological information of patients in pre-hospital medical care for our large and medium-sized cities and probe the patients' characteristic. Method The data in 2008 were exported from the computer databases of 8 large and medium-sized cities' emergency medical centers in our country.The thorough records of data were conducted to statistical analysis. Results ( 1 ) The scheduling time, running time, rescue time, returning time, total time and service radius in the pre-hospital medical care group were 2.16± 1.10(min), 14.01 ±6.82(min), 12.12±5.96(min), 14.08± 6.85(min), 42.34± 20.21(min)and 8.50±4.18(km), and the above parameter in the non-death group were 2.19 ± 1.13(min), 14.15 ± 7.14(min),11.60±6.72(min), 14.92 ±6.89(min), 41.86± 19.53(minutes) and 8.63±4.31(Km), and the above parameter in the death group were 2.10± 1.08(min), 13.68 ± 7.14(min), 25.25 ± 12.34(min), 13.75±6.48(min), 54.74 ± 25.47(min) and 7.86± 3.91(Km), and the above parameter in the non-sudden cardiac death group were2.09± 1.03(min), 13.58±6.78(min), 25.53± 12.34(min), 13.60± 6.54(min), 53.79±23.77(min) and 7.67 ± 3.86(Km), and the above parameter in the sudden cardiac death group were 2.12 ±1.02(min), 14.10±7.05(min), 24.79± 12.08(min), 13.79±6.61(min), 54. 80 ± 25. 36( min) and 7.90±3.92(Km) respectively. The scheduling time, running time, returning time and service radius in the death group were less than those of the non-death group, but the rescue time and total time of the former were more than those of the latter respectively ( P ＜ 0.05 or P ＜ 0. 001 ). The scheduling time and returning time didn' t have significant difference between the sudden cardiac death group and the non-sudden cardiac death group respectively ( P ＞ 0.05), but the running time, total time and service radius of the sudden cardiac death group were more than those of the non-sudden cardiac death group, and the rescue time of the former was less than that of the latter respectively ( P ＜ 0.05 or P ＜ 0.001 ). (2)The patients' amount in pre-hospital medical care group, the non-death group, the death group, the non-sudden cardiac death group and the sudden cardiac death group were at most in first quarter, and the least time slice of patients' amount were 4:00～ 6:00, 4:00～6:00, 4:00～ 6:00, 22:00～ 24:00, 2:00～4:00 respectively, and the most time slice of patients' amount were 20:00～ 22:00, 20:00～22:00, 8:00～ 10:00, 2:00 ～ 4:00, 8:00 ～ 10:00 respectively. (3)In 241 876 cases of pre-hospital medical care group, the patients' amount of trauma was at most, whose age grades was by far among21 ～50, and the others in sequence were nervous system, circulatory system, other group, digestive system, respiratory system and poisoning group respectively, whose age grades in nervous system, circulatory system and respiratory system was by far above 51, especially above 70. The patients' age grades in other group and digestive system had two climax age groups, which the one was 21 ～ 30, and the other was above 70. The patients' age grades in poisoning group was by far among 21 ～ 50, which the patients' amount of acute alcoholism was at the most. (4) In 12 568 cases of death group, the death amount of circulatory system, other group, respiratory system, nervous system and digestive system ranked at the lst,2nd,4th,5th 8th respectively, whose age grades was by far above 51, especially above 70,and the patients' amount of sudden cardiac death was at the most in the death amount of circulatory system. The death amount of trauma and poisoning group ranked at the 3rd, 6th respectively, whose age grades was by far among 21 ～ 50. (5)The total amount, the death amount and the sudden cardiac death amount of male patients were more than those of female patients. (6)The percentage of the death group to the pre-hospital medical care group was 5.20%, and the percentage of the sudden cardiac death group to the pre-hospital medical care group was 1.29%,and the percentage of the sudden cardiac death group to the death group was 24.87 %, and the percentage of the sudden cardiac death group to the circulatory system group was 67.33 %. Conclusions ( 1 )The trauma and the sudden cardiac death are the overriding reason of disease and the overriding reason of death in our large and medium-sized cities respectively. (2) It is very important to cut the death rate of the middle-old age patients by strengthening prevention and cure of cardiovascular and cerebrovascular diseases, discerning the critical illness early and improving the level of pre-hospital medical care. (3)It is a strong method to decrease the total amount and the death amount of the trauma, especially in traffic accident, by strengthening safety in production, observing traffic regulation and enhancing the legal awareness.