A GRIP-1-EZH2 switch binding to GATA-4 is linked to the genesis of rhabdomyosarcoma through miR-29a.

Terminal differentiation failure is an important cause of rhabdomyosarcoma genesis, however, little is known about the epigenetic regulation of aberrant myogenic differentiation. Here, we show that GATA-4 recruits polycomb group proteins such as EZH2 to negatively regulate miR-29a in undifferentiated C2C12 myoblast cells, whereas recruitment of GRIP-1 to GATA-4 proteins displaces EZH2, resulting in the activation of miR-29a during myogenic differentiation of C2C12 cells. Moreover, in poorly differentiated rhabdomyosarcoma cells, EZH2 still binds to the miR-29a promoter with GATA-4 to mediate transcriptional repression of miR-29a. Interestingly, once re-differentiation of rhabdomyosarcoma cells toward skeletal muscle, EZH2 was dispelled from miR-29a promoter which is similar to that in myogenic differentiation of C2C12 cells. Eventually, this expression of miR-29a results in limited rhabdomyosarcoma cell proliferation and promotes myogenic differentiation. We thus establish that GATA-4 can function as a molecular switch in the up- and downregulation of miR-29a expression. We also demonstrate that GATA-4 acts as a tumor suppressor in rhabdomyosarcoma partly via miR-29a, which thus provides a potential therapeutic target for rhabdomyosarcoma.

Application of "priority approach of uncinate process" in laparoscopic pancreaticoduodenectomy:A report of 200 cases / 中国实用外科杂志

OBJECTIVE: To explore the value of "priority approach of uncinate process" in laparoscopic pancreaticoduodenectomy. METHODS: The data of 200 patients who underwent laparoscopic pancreaticoduodenectomy in the No.2 Department of Hepatobiliarypancreatic Surgery, the First Hospital of Jilin University from April 2015 to October 2018 were analyzed retrospectively. RESULTS: All the 200 patients successfully completed laparoscopic pancreaticoduodenectomy, including 1 case of laparoscopic pancreaticoduodenectomy combined with right hemicolectomy,2 cases of laparoscopic pancreaticoduodenectomy combined with pancreaticocotailectomy,and 2 cases of laparoscopic pancreaticoduodenectomy combined with portal vein reconstruction(end-to-end anastomosis). The mean operation time was(281±49)min,including the specimen removal time(91±15)min,and the intraoperative blood loss was 50-850 mL(122±53)mL. The mean postoperative hospital stay was(16±9)days. Eight-teen cases(9.0%)had grade B pancreatic fistula and 3 cases(1.5%)had grade C pancreatic fistula. Postoperative anastomotic bleeding in 2 cases(1.0%). Intraperitoneal hemorrhage was found in 14 cases(7.0%), and delayed gastric emptying in 9 cases(4.5%).Biliary fistula was found in 11 cases(5.5%). There were 2 deaths(1.0%). Postoperative pathological diagnosis showed that ductal adenocarcinoma of the head of pancreas was in 33 cases(16.5%),the pancreas intraductal papillary mucinous tumor in 15 cases(7.5%),head of the pancreatic neuroendocrine tumors in 6 cases(3.0%),pancreatic ductal epithelial hyperplasia in 1 case(0.5%),solid pancreatic head fake papilloma in 9 cases(4.5%),pancreatic head capsule adenomas in 5 cases(2.5%),chronic pancreatitis in 1 case(0.5%),duodenal adenocarcinoma in 4 cases(2.0%), duodenal stromal tumor in 2 cases(1.0%), duodenal benign space-occupying lesions in 11 cases(5.5%),periampullary carcinoma of non pancreatic head origin in 105 cases(52.5%)and benign periampullary tumors in 9 cases(4.5%). CONCLUSION: "Priority approach of uncinate process" is safe,rapid and effective in laparoscopic pancreaticoduodenectomy,which is worthy of further promotion and application in clinic.

EGF Protects Cells Against Dox-Induced Growth Arrest Through Activating Cyclin D1 Expression.

It has been reported that the antitumor drug doxorubicin (Dox) exerts its toxic effects via GATA-4 depletion and that over-expression of GATA-4 reverses Dox-induced toxicity and apoptosis; however, the precise mechanisms remain unclear. In this study, we observed, for the first time, that EGF protects cells against Dox-mediated growth arrest, G2/M-phase arrest, and apoptosis. Additionally, EGF expression was down-regulated in Dox-treated cells and up-regulated in GATA-4 over-expressing cells. Utilizing real-time PCR and western blotting analysis, we found that the expression of the cell cycle-associated protein cyclin D1 was inhibited in GATA-4-silenced cells and Dox-treated cells and was enhanced in GATA-4 over-expressing cells and EGF-treated cells. Furthermore, EGF treatment reversed the inhibited expression of cyclin D1 that was mediated by GATA-4 RNAi or Dox. Our results indicate that EGF, as a downstream target of Dox, may be involved in Dox-induced toxicity as well as in the protective role of GATA-4 against toxicity induced by Dox via regulating cyclin D1 expression, which elucidates a new molecular mechanism of Dox toxicity with important clinical implications.

EGF is required for cardiac differentiation of P19CL6 cells through interaction with GATA-4 in a time- and dose-dependent manner.

The regulation of cardiac differentiation is critical for maintaining normal cardiac development and function. The precise mechanisms whereby cardiac differentiation is regulated remain uncertain. Here, we have identified a GATA-4 target, EGF, which is essential for cardiogenesis and regulates cardiac differentiation in a dose- and time-dependent manner. Moreover, EGF demonstrates functional interaction with GATA-4 in inducing the cardiac differentiation of P19CL6 cells in a time- and dose-dependent manner. Biochemically, GATA-4 forms a complex with STAT3 to bind to the EGF promoter in response to EGF stimulation and cooperatively activate the EGF promoter. Functionally, the cooperation during EGF activation results in the subsequent activation of cyclin D1 expression, which partly accounts for the lack of additional induction of cardiac differentiation by the GATA-4/STAT3 complex. Thus, we propose a model in which the regulatory cascade of cardiac differentiation involves GATA-4, EGF, and cyclin D1.

Development and prospect of dynamic dummy research / 医用生物力学

The dynamic dummy plays an important role in the research of protecting human beings from impact environment. To collect data from dummy in dangerous impact tests is the fundamental method used in developing protection equipment and systems in aerospace, automobile and other industries. The performances of a dummy depend on its simulation degree, as well as the quality and quantity of sampled signals. The dummy technology abroad is now indispensable in developing the protection of aviation ejection and rescue system, and also beneficial to automobile and other industries. China had no Chinese characterized dummy applied until the year of 2003 when the dynamic dummy was created in Institute of Aviation Medicine, and the dummy has equivalent high performance as that made by the United States and has been availably exerted in aviation. For evaluating the impact injuries on Chinese human beings, it is necessary to further develop Chinese characterized dummy series, and to establish the all-around criteria by strengthening application of digital virtual dummy in impact environment study.

Pilot load analysis under Herbst maneuver based on flight simulation / 医用生物力学

Objective To obtain the multi-axis load histories on physiological coordinate of the pilot when performing Herbst maneuver by flight simulation, and make analysis on the obtained typical data. Methods The 3D geometrical model of the aircraft was established in CAD software based on design parameters of the fourth-generation aircraft, 6 key motion parameters of mass center were obtained by flight simulation, and 3D human body model was developed according to anthropometric measurement data of Chinese male pilot; based on the location of cabin and seat in the aircraft, the assembly model with both the aircraft and human body was established and the multi-axis load histories at different locations of human body under Herbst maneuver were obtained through kinematics analysis of the human-aircraft system. An analytic case of Herbst maneuver at altitude of 3 km and flight velocity of 90 m/s was carried out. Results The load histories at chest, foot and head of human body were basically coincided, but Gy histories between the chest and hand were different; the Gy peak value of hand was about 1.6 g; under the multi-axis loads, the +Gx peak value was about 3.0 g, being the maximum. Conclusions The load histories of aircraft mass center cannot be used as those of human body because it may have some deviation, and the Gy histories for hand cannot be replaced by load histories of other locations on human body when they are used for analysis on effects of multi axis load on operating behaviors of the aircraft.

Insulin induces proliferation and cardiac differentiation of P19CL6 cells in a dose-dependent manner.

Insulin is a peptide hormone produced by beta cells of the pancreas. The roles of insulin in energy metabolism have been well studied, with most of the attention focused on glucose utilization, but the roles of insulin in cell proliferation and differentiation remain unclear. In this study, we observed for the first time that 10 nmol/L insulin treatment induces cell proliferation and cardiac differentiation of P19CL6 cells, whereas 50 and 100 nmol/L insulin treatment induces P19CL6 cell apoptosis and blocks cardiac differentiation of P19CL6 cells. By using real-time polymerase chain reaction (PCR) and Western blotting analysis, we found that the mRNA levels of cyclin D1 and α myosin heavy chain (α-MHC) are induced upon 10 nmol/L insulin stimulation and inhibited upon 50/100 nmol/L insulin treatment, whereas the mRNA levels of BCL-2-antagonist of cell death (BAD) exists a reverse trend. The similar results were observed in P19CL6 cells expressing GATA-6 or peroxisome proliferator-activated receptor α (PPARα). Our results identified the downstream targets of insulin, cyclin D1, BAD, α-MHC, and GATA-4, elucidate a novel molecular mechanism of insulin in promoting cell proliferation and differentiation.

Insulin induces C2C12 cell proliferation and apoptosis through regulation of cyclin D1 and BAD expression.

Insulin is a secreted peptide hormone identified in human pancreas to promote glucose utilization. Insulin has been observed to induce cell proliferation and myogenesis in C2C12 cells. The precise mechanisms underlying the proliferation of C2C12 cells induced by insulin remain unclear. In this study, we observed for the first time that 10 nM insulin treatment promotes C2C12 cell proliferation. Additionally, 50 and 100 nM insulin treatment induces C2C12 cell apoptosis. By utilizing real-time PCR and Western blotting analysis, we found that the mRNA levels of cyclinD1 and BAD are induced upon 10 and 50 nM/100 nM insulin treatment, respectively. The similar results were observed in C2C12 cells expressing GATA-6 or PPARα. Our results identify for the first time the downstream targets of insulin, cyclin D1, and BAD, elucidate a new molecular mechanism of insulin in promoting cell proliferation and apoptosis.

Dynamic responses of head-neck complex in pilots during arrested deck landing / 医用生物力学

Objective To analyze the dynamic response and strain of the major muscles in head-neck complex of pilot with or without wearing the helmet during carrier aircraft arrested deck landing. Methods Ten-rigid body dynamic model of human head-neck complex was created including head, seven cervical vertebrae and two thoracic vertebrae; mechanical properties of the ligaments, intervertebral discs and other surrounding soft tissues were described by lumped parameter method; mechanical properties of the 15 pairs of muscles in this human head-neck complex were represented by non-linear stress-strain relationship. The model was validated by using experimental data of dynamic responses from the human head-neck complex in a set of different types of automobile crashes. Results The overload curve and strain of this 15 pairs of muscles in head-neck complex of the pilot during arrested deck landing were obtained. The results showed that the extension of splenius cervicis was the largest. The strain of splenius cervicis could reach 50% when the pilot wore the helmet, and it could reach as high as 56% if the helmet’s weight was 2.7 kg. Conclusions Wearing helmet would extend the stretch of neck muscles, and the simulation result could be used for further evaluation on head/neck injury of the pilot.

Study on neck injuries in military pilots / 医用生物力学

Objective To investigate the present situation of neck injuries in military pilots, analyze possible factors that induce neck injuries and how such injuries could influence flight training, and provide suggestions for relevant physiological researches and engineering solutions. Method Questionnaires were carried out among 1 924 military pilots, including pilots of primary trainer, attacker, fighter, bomber, transporter and helicopter. The questionnaire consist of 2 parts: (1) pilots’ basic information, such as unit, age, type of aircraft, flying hours, height, weight, etc. (2) relevant issues on neck injuries, including symptoms and their influences on flight, reasons that cause the injuries, etc. Statistical analyses were conducted according to the questionnaire results. Results The investigation showed that 71.3% of the pilots had uncomfortable neck symptoms and 60.4% of them had befallen such symptoms during flight. 33.7% of the pilots had suffered neck pain and 19.2% of them reported that such pains took place during flight. Factors such as acceleration, weight of helmet and long duration of flight would be the main reasons resulting in the discomfort of neck. Bomber pilots showed the highest proportion either on the neck discomfort or on the neck pain. Conclusions Neck injuries have become the frequently occurring illness in Chinese military pilots and have affected their daily flight. The study also foresees an increased tendency on pilots’ neck injuries due to the growing requirements of flight load and training strength on fighter and attacker pilots. Therefore, great importance should be attached on neck injuries of military pilots and further studies should be conducted on physiological investigations and engineering solutions.

Application of emulational trunk dummy in evaluating the opening shock of life saving parachute / 医用生物力学

Objective To carry out quantitative investigation on application of emulational trunk dummy (ETD) in evaluating the opening shock of life saving parachute and provide a more reliable test method for further development. Method ETD equipped with parachute was tested in the impact experiment, where a 63.4 kg impact block was dropped from the height of 0.20 m，0.40 m，0.60 m，0.80 m respectively to simulate different opening shocks. The opening shocks were deducted by measured forces on harness and acceleration loads at the center of dummy's thorax. For comparison, 5 rigid trunk dummies (RTD) were tested under the equivalent impacts. As the contrast test, 24 male healthy subjects were also exposed under such impacts with standing and sitting posture respectively. Results Under the same impact, the peak impact value on harness exhibited maximum on RTD, minimum on subjects with sitting posture, and medium on ETD. There were significant differences between each experimental group (P<0.01). With different impact loads, the peak impact value on ETD was 2 795，3 873，4 816 and 5 736 N respectively, which was correspondingly close to that of subjects with standing posture(2 541，3 042，3 720 and 4250 N). Conclusions The result of opening shock gathered from ETD is closer to that from RTD due to ETD’s viscoelasticity, which shall certainly influence the measured opening shock. Therefore, ETD is suggested to be used in the development of live saving parachute.

Biomechanics in aviation / 医用生物力学

Pilots are usually under various different mechanical loads during flights, which can affect their musculoskeletal and cardiovascular system and even bring them injuries. Biomechanics mainly studies the mechanics and mechanobiology in medicine and biology. Aviation biomechanics studies the physiological response to different complicated mechanical loads during flights and the countermeasures. The research fields of aviation biomechanics include: mechanical loads on human body injury and related countermeasures, durative loads, vibration and noise on the physiological effects of human body and related comtermeasures, etc.