Suppression of HMGB1 inhibits neuronal autophagy and apoptosis to improve neurological deficits in rats following intracerebral hemorrhage / 南方医科大学学报

OBJECTIVE@#To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats.@*METHODS@#Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA.@*RESULTS@#The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05).@*CONCLUSION@#Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.

Exploration and practice of developing top-notch innovative medical personnel based on research-oriented hospital with thick cultivation culture / 中华医学教育探索杂志

In response to the major national strategic needs of "Healthy China" and "Innovation-Driven Development", Sichuan University, as a pilot university of "Excellent Doctor Education and Training Plan-Top Innovative Medical Personnel Training", has been exploring the training strategies since 2012. On the basis of the international theory of "The Third Generation of Medical Education based on Health System", we have innovatively put forward the new era of "Med+" education theory based on research-oriented hospitals (with medical/research/translational facility) and the two-level training paradigm from "cultivating professionalism" to "notch up to top" by planting three cultures. We have also developed a competency training system of "Five Integrated Curricula and Five Teaching & Learning Strategies". We have shifted from "didactic teaching" to "formative learning", edifying excellent doctors with "professionalism culture". We have initiated two kinds of top-notch plans, constructed a "1+2+3" innovation and entrepreneurship education system, explored "transformative learning" to incubate compound top-notch personnel with "innovative culture", opened up a "school-hospital unified" administrative system, built a PDCA closed-loop of quality control supported by mobile technology, and recast the "quality culture" to ensure shifting from "cultivating professionalism" to "notch up to top".

Research on innovative training model of medical undergraduate talents combining teaching and research / 中华医学教育探索杂志

The combination of teaching and research is an innovative training mode of medical undergraduate education in the new era, which aims to play the interaction of teaching with research, and promote this model while driving the innovation of the curriculum teaching system, thus propelling the medical undergraduate education in China to a new level. On the premise that basic teaching is fully guaranteed, in order to better construct and popularize the innovative mode, students, teachers and schools need to communicate and integrate repeatedly, and carry out the innovation training of scientific research throughout the whole process of medical undergraduate education. Students need to establish correct research values, teachers should renew their educational concepts and improve their sense of responsibility during the training of innovative medical undergraduate talents, and schools need to strengthen the supervision of students' scientific research and innovation activities and continuously improve relevant systems.

Comparison of surgical clipping and intravascular interventional therapy in treatment of intracranial wide-necked aneurysm / 中国医师进修杂志

Objective To compare the clinical effects and safety of surgical clipping and intravascular interventional therapy in treatment of intracranial wide-necked aneurysm.Methods The clinical data of 158 patients with intracranial wide-necked aneurysm from February 2010 to February 2013 were retrospectively analyzed,all patients were divided into two groups:surgical clipping group with 92 cases and intravascular interventional therapy group with 66 cases,the postoperative curative effects,treatment time,hospital stay,hospital expenses and postoperative complications between two groups were compared.Followed up for 10-46 months,the recurrence rate were compared.Results The good prognosis and defective rates between surgical clipping group and intravasular interventional therapy group had no significant difference [90.2％(83/92) vs.90.9％(60/66),9.8％(9/92) vs.9.1％ (6/66)] (x2 =0.298,P ＞ 0.05).The preoperative Hunt-Hess classification and CT Fisher classification between two groups had no significant difference (P ＞ 0.05).Six months after discharge,mRS score was used to evaluate the curative effect,the defective rates in same level patients between two kinds of treatment methods had no significantdifference (P ＞ 0.05).The treatment time,hospital stay in surgical clipping group were significantly longer than those in intravascular interventional therapy group [(4.03 ± 1.01) h vs.(1.61 ± 0.98) h,(15.90 ± 2.03) dvs.(13.20 ± 1.95) d],hospital expenses was significantly lower than that in intravascular intervention therapy group [61 829.4 ±320.6) yuan vs.(99 876.2 ±371.5) yuan] (P ＜0.05).The postoperative complications rate between two groups had no significant difference (P ＞ 0.05).Followed up for 31.3 (10-46) months,the recurrence rate in surgical clipping group was significantly lower than that in intravascular intervention therapy group [1.1％ (1/94) vs.8.8％ (6/68)] (P ＜ 0.05).Conclusion Surgical clipping and intravascular interventional therapy in treatment of intracranial wide-necked aneurysm has their own different characteristics,so patients' treatment methods should be based on their preoperative status (especially preoperative Hunt-Hess and Fisher classification) and patients' economic conditions.

Clinical observation of using surgery to treat hypertensive intracerebral hemorrhage (HICH) patients / 中国基层医药

Objective To discuss the clinical effects of using CT positioning keyhole approach to treat hy-pertensive intracerebral hemorrhage (HICH).Methods 85 cases of patients with hypertensive intracerebral hemor-rhage(HICH) were chosen and divided into two groups according to the operation methods:the observation group had 55 cases given CT positioning keyhole approach ,while the control group had 30 cases treated with traditional cranioto-my hematoma removal operation .All patients were supplemented by postoperative blood pressure control and nutrition -al support treatment .The average operation time ,hematoma disappearing time ,the length of hospital stay and re-bleed-ing rates and postoperative ability of daily life ( ADL) scores of the two groups were all carefully recorded and com-pared.Results The average operation time,hematoma disappearing time and hospital stay of the observation group were (66.5 ±12.8)min,(3.4 ±1.3)d,and (9.3 ±1.7)day which were all significantly lower than those of the con-trol group(193.5 ±23.7)min,(5.8 ±2.1)d and (15.2 ±3.8)d;T-test values of the two groups were 2.874,3.125 and 3.433 separately(P0.05).6 months′follow-up after opera-tion,in the control group 2 cases were lost to follow-up while in the observation group 3 cases were lost to follow-up;Using ADL to evaluate the two groups of patients with survival and continuous follow-up,we found that the observation group′s postoperative quality of life was better than that of the control group′s(μ=3.325,P<0.05).Conclusion Using CT positioning keyhole approach has smaller trauma , shorter operation time and faster postoperative recovery and other characteristics,which is an effective method for the treatment of hypertensive intracerebral hemorrhage(HICH).

Relationship between amyloid beta-protein and oxidative stress and the protective role of pituitary adenylate cyclase activating polypeptide against oxidative stress induced damage on neuro-2a cells / 中国应用生理学杂志

<p><b>AIM</b>To observe the relationship between amyloid beta-protein (Abeta) and oxidative stress and the protective role of pituitary adenylate cyclase activating polypeptide (PACAP, PACAP-27) against damage induced by oxidative stress (H2O2) in neurem-2a cells.</p><p><b>METHODS</b>With cultured neuro-2a cells the cell survival and apoptosis were measured by MTT assay, Hoechest33258 staining, DNA ladder and the percentage of small DNA fragment.</p><p><b>RESULTS</b>Concentration-dependent toxicity was induced with H2O2 treatment for 24 h. The neurotoxicity of H2O2 was increased by about 10 times with cotreatment neurons with amyloid beta-protein fragment 25-35 (Abeta(25-35)). While decrease the percentage of small DNA fragmentation the cell survival was increased with co-treatment with PACAP-27(which were added to the culture everyday). The effect of PACAP was not reversed with antagonist of PACAP receptor, PACAP(6-27).</p><p><b>CONCLUSION</b>Abeta and H2O2 can promote each other's neurotoxicity. Cultured neurons were protected by PACAP27 from the neurotoxicity of H2O2 but not through the activation of PACAP-27 receptor.</p>

Pituitary adenylate cyclase activating polypeptide protects neuro-2a cells from beta amyloid protein cytotoxicity by modulating intracellular calcium / 生理学报

MTT analysis and intracellular calcium measurement by using confocal laser scanning microscopy were used to study the possible mechanism of protective effect of pituitary adenylate cyclase activating polypeptide 27 (PACAP27) from beta amyloid protein (Abeta)-induced neurotoxicity. The results showed that treatment with PACAP (less than 0.1 micromol/L) increased the survival and reproductive ability of neuro-2a cells and protected the neuro-2a cells from being injured by Abeta. The protective effect of PACAP27 was reversed by the competitive PACAP receptor antagonist PACAP6-27. An increase in intracellular calcium was observed when the cells were challenged with Abeta and PACAP. But the calcium increase induced by Abeta kept stable for a long time while PACAP caused a transient rise in intracellular calcium. The intracellular calcium increase induced by Abeta was blocked by pretreatment with PACAP for 10 min. It is suggested that the neuroprotective effect of PACAP against neuronal damage induced by Abeta may result from its role in inhibiting the sustained rise in intracellular calcium.

Activation of PACAP receptor could protect cultured hippocampal neurons against beta amyloid peptide induced neurotoxicity / 中国应用生理学杂志

<p><b>AIM</b>To observe the protective role of pituitary adenylate cyclase activating polypeptide (PACAP) on hippocampal neuronal apoptosis induced by beta amyloid peptide in the culture.</p><p><b>METHODS</b>Hippocampal neurons were isolated from 1d old SD rat and neuronal survival and apoptosis were measured by MTT assay and DNA ladder.</p><p><b>RESULTS</b>25 micromol/L Abeta could induce neuron apoptosis while co-treatment with PACAP could increase the survival of hippocampal neurons. The antagonist of PACAP receptor, P6-27, could reverse the effect of PACAP.</p><p><b>CONCLUSION</b>PACAP could protects cultured neurons from the neurotoxicity of Abeta through the activation of PACAP receptor and may have a bright use in treatment of neurodegenerative disease.</p>

Protective effect of Shenfu injectio pretreatment on myocardium against ischemia-reperfusion injury in diabetic rabbits / 中华麻醉学杂志

Objective To investigate the protective effect of pretreatment with Shenfu injectio(SFI)on myocardium against ischemia-reperfusion(I/R)injury in diabetic rabbits.Methods Forty healthy adult male rabbits weighing 2.4-3.2 kg were used in this study.Type I diabetes mellitus was induced by intravenous alloxan 120 mg?kg~(-1) and confirmed by fasting blood glucose＞11.1 mmol?L~(-1).The animals were randomly divided into 5 groups(n=8 each):groupⅠsham operation;groupⅡI/R and groupⅢ,Ⅳ,ⅤSFI+I/R.I/R was produced by occlusion of the anterior descending branch of left coronary artery(LAD)for 60 min.The occlusion of LAD was then released for reperfusion.In sham operation group(Ⅰ)LAD was exposed but not occluded.In groupⅢ,ⅣandⅤSFI 5,10 and 15 ml?kg~(-1) was givenⅣrespectively 30 min before myocardial ischemia.MAP,HR,left ventricular developed pressure(LVDP),?dp/dt_(max),left ventricular end-diastolic pressure(LVEDP)and Vmax were recorded immediately before ischemia(T_0,baseline),at 5 min of ischemia(T_1),immediately before reperfusion(T_2)and at 5,15,60,90,120 min of reperfusion(T_(3-7)).The animals were killed and hearts removed for determination of infarct size and microscopic examination of the ultrastructure of LAD using transmission electron microscope.Results MAP,HR,LVDP,?dp/dt_(max) and Vmax were significantly decreased while LVEDP was significantly increased during reperfusion as compared to the baseline values at T_0 in I/R group. I/R produced myocardial infarct and damage to the endothelial cells of LAD.The harmful effect of I/R was attenuated by different doses of SFI.SFI 10 ml?kg~(-1) provided best effect.Conclusion Pretreatment with SFI can protect the myocardium against I/R injury in diabetic rabbits.SFI 10 ml?kg~(-1) produces better effect.

TREATMENT OF TOTAL AVULSION THE WHOLE HAND WITH DIGITAL NERVES PRESERVATION AND UPPER ABDOMINAL BAG-SHAPED SKIN FLAP / 解放军医学杂志

The treatment of total avulsion of the hand is somewhat difficult and the result usually not satisfactory. Four cases of such patients were treated from 1983 to 1987. After routine debridement, digital nerves and its surrounding adipose tissue were preserved. An "S" shape skin flap was designed an raised in the contralateral upper abdominal quadrant to cover the injured hand like a bag, so that both sides of the hand were covered. The donor area (12cm2) was directly sutured. Nerve endings might grow into the flaps because of the preservation of digital nerves. Three patients were followed-up for 2 to 6 years, the injured hands regained good pain sensation as well as stereognostic and temperatuer sensations. The function of the hand is satisfactory, but the flap looked bulky and multiple plastic operations were necessary to seperate the fingers.