BACKGROUND: P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. METHODS: A zinc finger protein-based P16 -specific DNA methyltransferase (P16-Dnmt) vector containing a "Tet-On" switch was used to induce extensive methylation of P16 CpG islands in normal human fibroblast CCD-18Co cells. Battery assays were used to evaluate cell immortalization and transformation throughout their lifespan. Cell subcloning and DNA barcoding were used to track the diversity of cell evolution. RESULTS: Leaking P16-Dnmt expression (without doxycycline-induction) could specifically inactivate P16 expression by DNA methylation. P16 methylation only promoted proliferation and prolonged lifespan but did not induce immortalization of CCD-18Co cells. Notably, cell immortalization, loss of contact inhibition, and anchorage-independent growth were always prevalent in P16-Dnmt&TERT cells, indicating cell transformation. In contrast, almost all TERT cells died in the replicative crisis. Only a few TERT cells recovered from the crisis, in which spontaneous P16 inactivation by DNA methylation occurred. Furthermore, the subclone formation capacity of P16-Dnmt&TERT cells was two-fold that of TERT cells. DNA barcoding analysis showed that the diversity of the P16-Dnmt&TERT cell population was much greater than that of the TERT cell population. CONCLUSION P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
Humans ; Telomerase/genetics* ; DNA Methylation/physiology* ; Fibroblasts/cytology* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cell Line ; Cell Transformation, Neoplastic/genetics*

This article introduced the background,drafting process,and main content of the Interim Measures for the Management of Surplus Drugs in Medical Institutions of Hubei Province(referred as the Measures).It focused on explaining the definition of surplus drugs and analyzing the requirements for drug dismantling,surplus drug billing,recovery and use procedures,special fund management,and duties and responsibilities of management departments.This paper aimed to guide readers to learn the Measures,understand the Measures and implement the Measures.It would help to improve the efficiency of medical resources,ensure medication safety,reduce patients'medication burden,and promote the rational use of medical insurance funds.

Objective:Principal Investigator (PI) system is the most common model of scientific research organization and management in colleges and universities. PI is the head of the laboratory or the leader of the research team who has the authority to manage the supporting team, funds, and space (laboratory). We aim to explore the advantages and problems of the PI system implementation and deeply understand how to effectively and scientifically manage the project management, personnel coordination, and fund use of the entire team to promote the scientific research output of the PI platform of medical schools in China.Methods:By concluding and analyzing the management experience and main bottlenecks of PI laboratories at home and abroad, and summarizing our center's experience in assisting the management of PI laboratories in life sciences, we explored a new model of PI system development suitable for China.Results:Under PI system, the person in charge systematically learns to operate his or her laboratory scientifically. Perfection and improvement of the methodologies of team formation, laboratory public affairs management, and laboratory fund management can effectively avoid existing problems and follow the intrinsic laws of scientific research development and truth-seeking, promote the development in discipline development, interdisciplinary cooperation, personnel training, and study style construction.Conclusions:As the leader and manager of the scientific research team, PI is critical to the development of scientific research in universities in China. The incubation of a new scientific management model for the PI team is conducive to promoting the scientific and technological innovation of the PI team and the long-term development of scientific research institutions.

Sarcopenia etiology is diverse and the pathogenesis is complex.It is closely related to limited activity, malnutrition and a variety of clinical diseases, which seriously affects the quality of life in the elderly and has become a global common health problem.This review focuses on the literature of non-drug interventions for sarcopenia in the past five years, focusing on the relationship of multimodal exercise, intestinal flora, parenteral nutrition and comprehensive intervention with sarcopenia, in order to provide a new basis for formulating scientific and effective non-drug intervention for sarcopenia.

Objective:To investigate the current situation of standardized patient programs and standardized patient educators in China, and to analyze the existing problems in the implementation.Methods:Questionnaire survey was used in this study. The questionnaire was made by Delphi method, and distributed via E-mails or through the internet to medical colleges, affiliated hospitals and general hospitals across the country. Microsoft Office Excel 2016 was used for data reduction and analysis and cartography.Results:A total of 94 medical colleges and hospitals of 27 provinces and municipalities participated in the survey, of which 43.62% had carried out standardized patient programs. The primary factor affecting the program implementation was the lack of standardized patient educators. The existing trainers were mainly clinicians or nurses, and the main way of training the educators was to send them to other universities for learning. A majority of respondents (94.68%) think it is necessary to establish and formulate a unified national certification system for standardized patient educators.Conclusion:The development of standardized patient program is unbalanced in China, and the lack of standardized patient educators has become the primary factor restricting the development. In order to make standardized patients a greater role in medical education, we should encourage different types of personnel to join in the standardized patient training team, to clarify the responsibilities of standardized patient educators, to standardize the process of trainers training, and to establish the certification system of standardized patient educators.

Objective:To observe the effect of mechanical vibration on the expression of microRNA-214-3p and serum interleukin-1β (IL-1β) in the broken ends of fractured bones in ovariectomized rats.Methods:Thirty 3-month-old female Wistar rats were randomly divided into a control group, a model group, and a vibration group, each of 10. An operation of ovariotomy was performed in those of the model and vibration groups to establish osteoporosis model. Five months later a model of mid femur fracture was made with animals in all the groups. Five days after their fracture, the vibration group received 20 minutes of whole-body vibration treatment at 35Hz for 5 days a week, while the control group and the model group received natural rearing without any additional intervention At 2 and 6 weeks after the operation, the Lane-Sandhu X-ray scoring system was used to evaluate the quality of fracture healing, and reverse-transcription polymerase chain reactions and enzyme-linked immunosorbent assays were used to detect miR-214-3p in the fractured bones and the serum levels of IL-1β.Results:At 2 weeks and 6 weeks after the operation the average growth score of the broken ends in the model group was significantly lower than that of the control group, while that of the vibration group was significantly higher than the model group′s average. Compared with the control group at the same time point, the average miR-214-3p content of the model and vibration groups was significantly higher 2 and 6 weeks after the surgery. Compared with the model group, the average level of miR-214-3p of the fractured ends of the vibration group was significantly lower at 6 weeks. Two and six weeks after the surgery, the average IL-1β of the model group was significantly higher than the control group′s average, and that of the vibration group was significantly lower.Conclusion:Mechanical vibration can promote osteoporotic fracture healing by inhibiting the expression of miR-214-3p and reducing the level of IL-1β at the broken ends of fractured bones.

Objective:To understand the HIV antibody screening results among the preoperative examination patients in Beijing Tongren Hospital from 2008 to 2018.Methods:A retrospective analysis of the HIV antibody screening data of thepreoperative examination patients from 2008 to 2018 in Beijing Tongren Hospital was performed with software SPSS19.0. Trend chi-square was used to analyze the positive rate, age, marital status, household registration and so on.Results:Among the 750 013 clinical patients, 428 (0.057%) cases were screened anti-HIV positive and 370(0.049%) cases were confirmed anti-HIV positive when detected with western blotting.Most of the HIV-infectedindividuals were non-Beijing nationality, accounting for 60.27%.Among the 370 HIV-infected patients, there were 334 males (90.27%) and 36 females (9.73%). The age was distributed mainly between 20-40 years old (62.43%), secondly between 40-60 years old (28.65%).361 (97.57%)HIV-infected cases were transmitted by the sex and the MSM men increased from 2008 to 2018 (trend χ2=7.307, P=0.007). There were 22 cases (5.95%) with HBsAg positive, 11 cases (2.97%) with anti-HCV positive. Among the 159 HIV-positive patients (42.97%) companied with syphilis specific antibody positive, there were 64 cases (17.30%) with TRUST tests positive. Additionally, 178 (48.11%) HIV-infected patientsfirst visited doctors because of ocular disease in the hospital; secondly, 71 (19.19%) HIV-infected patientsfirst visited the dermatology. Conclusions:The number of HIV-infected patientsmarkedly increased from 2008 to 2018. The sexual transmission is still the main pathway for HIV infection, particularly homosexual transmission. Moreover, the results indicate that it is necessary to detect HIV antibody for the ocular disease patients.

Objective:To understand the HIV antibody screening results among the preoperative examination patients in Beijing Tongren Hospital from 2008 to 2018.Methods:A retrospective analysis of the HIV antibody screening data of thepreoperative examination patients from 2008 to 2018 in Beijing Tongren Hospital was performed with software SPSS19.0. Trend chi-square was used to analyze the positive rate, age, marital status, household registration and so on.Results:Among the 750 013 clinical patients, 428 (0.057%) cases were screened anti-HIV positive and 370(0.049%) cases were confirmed anti-HIV positive when detected with western blotting.Most of the HIV-infectedindividuals were non-Beijing nationality, accounting for 60.27%.Among the 370 HIV-infected patients, there were 334 males (90.27%) and 36 females (9.73%). The age was distributed mainly between 20-40 years old (62.43%), secondly between 40-60 years old (28.65%).361 (97.57%)HIV-infected cases were transmitted by the sex and the MSM men increased from 2008 to 2018 (trend χ2=7.307, P=0.007). There were 22 cases (5.95%) with HBsAg positive, 11 cases (2.97%) with anti-HCV positive. Among the 159 HIV-positive patients (42.97%) companied with syphilis specific antibody positive, there were 64 cases (17.30%) with TRUST tests positive. Additionally, 178 (48.11%) HIV-infected patientsfirst visited doctors because of ocular disease in the hospital; secondly, 71 (19.19%) HIV-infected patientsfirst visited the dermatology. Conclusions:The number of HIV-infected patientsmarkedly increased from 2008 to 2018. The sexual transmission is still the main pathway for HIV infection, particularly homosexual transmission. Moreover, the results indicate that it is necessary to detect HIV antibody for the ocular disease patients.

Objective To evaluate the safety and effectiveness of enhanced recovery after surgery (ERAS) in laparoscopic radical gastrectomy for gastric cancer.Methods From May 2015 to July 2017,149 patients with gastric cancer in our department were prospectively enrolled and randomly divided into the ERAS group (n =75) and control group (n =74).Results In ERAS group compared to control group,the time to first passage of flatus was (51 ± 11)vs.(62 ± 11)h,first feeding time (46 ± 12) vs.(68 ±20)h,gastric tube removal time (13 ± 12)h vs.(70 ± 16) h,pain score on the first day after surgery (3.9 ±1.3) vs.(5.2 ±0.9),C-reaction protein level (8.5 ±2.6) mg/L vs.(10.1 ±3.0)mg/L,post-op hospital stay (6.9 ± 2.9) d vs.(11.2 ± 3.5) d,were all significantly different (all P ＜ 0.05).The postoperative complication rates was 25％ vs.28％ respectively,(x2 =0.101,P =0.750).Conclusions Enhanced recovery after surgery can promote the postoperative recovery and shorten the time of hospitalization in laparoscopic-assisted radical gastrectomy for gastric cancer.

Objective To identify the risk factors for postoperative complications after radical resection of rectal cancer, and study the influence of high ligation of the inferior mesenteric artery on postoperative complications of rectal cancer. Methods Clinical data of the patients who underwent radical resection of rectal cancer in the Affiliated Hospital of North Sichuan Medical College from January 2011 to December 2015 were analyzed. The χ 2test and t test were used for all the data. Results A total of 431 patients with rectal cancer were included, of which 80 cases were excluded, and finally 351 cases met the standard. Among them, 196 cases were in high ligation group, and 155 cases were in low ligation group. The total incidence of postoperative complications was 20.4 %(40/196) in the high ligation group and 27.1 %(42/155)in the low ligation group respectively,the difference of which was not statistically significant(χ2=1.336, P= 0.245). The incidence of anastomotic leakage was 10.2 % (20/196) in the high ligation group and 7.7 % (12/155) in the low ligation group respectively, and there was no significant difference between them (χ2=0.529, P= 0.467). Logistic regression analysis revealed that gender (OR= 2.102, 95 % CI 1.278-3.459, P=0.003), body mass index (OR= 2.492, 95 % CI 1.070-5.800, P= 0.027), with or without anemia before surgery(OR=2.203,95 % CI 1.085-4.472,P=0.029), and location of tumor(OR=2.861, 95 % CI 1.288-16.007,P=0.019) were independent risk factors for postoperative complications. Conclusions High ligation of the inferior mesenteric artery does not increase the incidence of postoperative complications after radical resection of rectal cancer. Anastomotic leakage after rectal cancer resection is related to gender, body mass index,with or without anemia before surgery,and location of tumor.