Research progress of Parkin protein regulating mitochondrial homeostasis through ubiquitination in cardiovascular diseases / 中国药理学通报

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Ischemic myocardial contracture occurred in early stage of asphyxia-induced cardiac arrest in rats / 中华急诊医学杂志

Objective:To investigate the characteristics of ischemic myocardial contracture after asphyxia-induced cardiac arrest (CA).Methods:Asphyxia and ventricular fibrillation (VF) induced cardiac arrest model was established. Thirty-one male Wistar rats were randomly(random number) assigned to the sham, asphyxia and VF groups. Electrocardiogram and blood pressure during CA stage were recorded. Arterial blood was drawn for blood gas analysis at 0 min after CA. The length and width of the heart were measured at 0,2,4,6 and 8 min after CA. The myocardial ATP contents were measured at 0 and 8 min after CA.Results:Compared with the VF group, the time of CA induction was longer in the asphyxia group[ (237±20 ) s vs (3±1) s, P<0.05]. At 0 min after CA, severe hypoxemia, carbon dioxide retention and acidosis had occurred in the asphyxia group, while these indexes in the VF group were basically normal. The length and width of the heart in the asphyxia group decreased gradually after CA, the myocardial contracture reached the limit around 6 min after CA, while the cardiac morphology of the VF group did not change significantly during the observation period of 8 min after CA. Myocardial ATP content in the asphyxia group decreased significantly at 0 min after CA ( P<0.05), while the difference between the VF group and the sham group was not statistically significant ( P>0.05). Conclusions:Myocardial contracture occurrs in the early stage of asphyxia CA, which may be related to ATP consumption in the asphyxia stage.

Effect of ultrasound-guided vacuum-assisted excision verus open surgery for benign phyllodes tumors of breast on postoperative local recurrence / 中华外科杂志

To examine the effect of VAE and open surgery on the postoperativelocal recurrence of benign phyllodes tumors of breast and to investigate the clinical efficacy of VAE in the treatment of benign phyllodes tumors. The clinical data of 128 patients with benign phyllodes tumors of breast admitted to the Guangdong Women and Children Hospital from January 2013 to January 2018 were retrospectively analyzed. All patients were female, aged (37.7±9.1) years (range: 16 to 56 years). Eighty patients underwent ultrasound-guided VAE (minimally invasive group) and 48 patients underwent open surgery (open group). The -test, χ(2) test or Fisher exact probability method were used to compare the clinical characteristics of the two groups of patients. Logistic regression was used to analyze the prognostic factors of postoperative local recurrence. The maximum diameter of tumor in the minimally invasive group was smaller than that in the open group ((20.6±7.4) mm . (42.0±2.0) mm, -7.173, 0.000). The follow-up time was (36.4±1.8) months (range: 12 to 71 months). There were 7 cases of local recurrences during the follow-up period. The local recurrence rates in the minimally invasive and open groups were 5.0% (4/80) and 6.3% (3/48). The results of multivariate analysis showed that the maximum tumor diameter of 25 mm was an independent prognosis factor for postoperativelocal recurrence (0.122, 95: 0.016 to 0.901, 0.039). While surgical procedure, age, menopausal status and history of fibroadenomas in the ipsilateral breast is not an independent prognostic factor for postoperative local recurrence. In the minimally invasive surgery group, the local recurrence rates were 2.9% (2/69) and 2/11 in patients with tumor maximum diameters<25 mm and ≥25 mm, respectively. Local recurrence of breast benign phyllodes tumors is closely related to the tumor size. For patients with tumor diameter25 mm, the postoperative local recurrence rate of VAE is low, which can be used in clinical practice. Intraoperative complete resection to achieve a negative surgical margin should be guaranteed to avoid local recurrence.

Sevoflurane reduces cerebral injuries in rats resuscitated from cardiac arrest through down regulating the expression of Bax and Bak / 中华急诊医学杂志

Objective To investigate the neuroprotective mechanism of sevoflurane in rats resuscitated from cardiac arrest (CA).Methods A ventricular fibrillation-induced CA model was established.Forty Wistar rats were randomly divided into the sham group,sevoflurane group and control group.Apoptosis-related proteins were measured by Western blot at 24 h after restoration of spontaneous circulation (ROSC).The status of mitochondrial permeability transition pore (MPTP) were measured using a spectrophotometer,and the mitochondrial membrane potential (MMP) were measured with JC-1 fluorescent probe.At 72 h after ROSC,the apoptotic index of neurons in hippocampal CA1 region was counted by TUNEL staining.Results The protein expression of Bax,Bak,cleaved-caspase 9,cleavedcaspase 3 and cytosolic cytochrome c were lower in the sevoflurane group (all P＜0.05),the protein expression of Bcl-2 was higher in the sevoflurane group compared with the control group (P＜0.05).The sevoflurane group had a less opening status of MPTP and a higher MMP compared with the control group (all P＜0.05).The sevoflurane group had less apoptotic neurons compared with the control group (P＜0.05).Conclusion By up-regulating the expression of Bcl-2,down-regulating Bax and Bak,sevoflurane could reduce the apoptosis of neurons and decrease the opening of MPTP,eventually reduce cerebral injuries.

Aconitum in treatment of rheumatoid arthritis: benefit-risk assessment / 中国中药杂志

Rheumatoid arthritis (RA) has the characteristics of long course of disease and difficulty in treatment. The conventional therapy may easily induce adverse drug reactions or events (ADR/ADE) due to the long-time medication. Thus, it should be given special attentions to treatment benefit and medication risk of RA patients. Aconitum, a kind of toxic traditional Chinese herbs, is an important complement therapy for RA, with some controversy in clinical application. Coming straight to the practical problem of combined use of traditional Chinese medicines (TCM) and Western medicines (WM), this study conducted quantitative assessment on the benefits and risks of Aconitum using combined with WM or not, which was carried out by the method of multi-criteria decision analysis model. RevMan 5.2 software was used to separately analyze the results of every index of 21 random clinical trials (RCTs) of Aconitum exclusive use in the treatment of RA, and 49 RCTs of Aconitum combined use with WM. The merged results indicated that as compared with the conventional therapy of WM, no matter the exclusive use or the combined use of Aconitum could improve the efficacy and decrease the incidence of ADR/ADEs. Based on the benefit-risk assessment decision tree of RA treatment, Hiview 3 software and Crystal Ball Monte Carlo simulation were used to calculate the benefit value, risk value and benefit-risk value of Aconitum exclusive use and the combined use of Aconitum with WM. The results showed that the combination therapy had significantly better benefits than Aconitum exclusive using, difference value was 15, (95%CI[9.72, 20.25]), but the risk of combined use was higher difference value=23, （95%CI[15.57, 30.55]）. In comprehensive consideration of the benefit and risk, the total benefit-risk value of using Aconitum alone was 58, while that of the combination therapy was 55, and the probability of the former superior to the latter was 81.07%. The study showed that Aconitum was the important therapy to supply RA treatment. In clinical application, the patient's acceptability of benefit and risk need to be considered; if patients cannot bear the risk, the combination use of Aconitum and WM is not recommended.

Advances in small molecular drugs targeted mutant p53 / 中国药理学通报

Tumor suppressor p53 protein can regulate the tran-scription of target genes, to control cell apoptosis, aging and other life activities,but mutant p53 is prone to losing antitumor function, thus promoting tumor development. At present, p53 protein has become one of the hot targets for the treatment of cancer. This article mainly introduces the structure and mechanism of small molecular compounds with restoring activity of mutant p53 as the target.

Gene transfer system mediated by PEI-cholesterol lipopolymer with lipid microbubbles / 药学学报

The properties of polyethyleneimine-cholesterol cationic lipopolymer (PEI-Chol) as gene carries and its gene transfer efficiency in vitro with lipid microbubbles were presented in this paper. PEI-Chol lipopolymer was synthesized by linking cholesterol chloroformate to the amino groups of branched poly(ethyleneimine) (PEI) of 1 800. The structure and molecular weight of PEI-Chol were confirmed by IR, 1H NMR and MADI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry), respectively. The average molecular weight of PEI-Chol was approximately 2 000. The gene delivery system of bubble/PEI-Chol/DNA was constructed by mixed PEI-Chol/pDNA (N/P 10:1) complexes with lipid microbubbles (2-8 microm) which were prepared by DPPC, DSPE-PEG2000 and perfluoropropane with the reverse phase evaporation technique. pEGFP-Cl (enhanced green fluorescent protein) was used as report gene to investigate the DNA condensing ability of PEI-Chol lipopolymer by agarose gel electrophoresis. And their cytotoxicity and in vitro transfer efficiency of different complexes were compared with each other in A549 and MCF-7. The results indicated PEI-Chol lipopolymer can condense plasmid DNA when N/P ratio upto 4, PEI-Chol complexes and bubble/PEI-Chol/DNA complexes were nontoxic to A549 and MCF-7 when formulated at the N/P ratio of 10/1 as determined by MTT assay. This bubble/PEI-Chol/DNA delivery system provided good transfer efficiency with other desirable characteristics such as against-precipitation of plasma proteins. In conclusion, bubble/PEI-Chol/DNA complex is a novel non-viral gene delivery system.

Effect of different ways of insulin infusion in parenteral nutrition patients on activation and concentration of insulin and blood glucose control:a prospective randomized comparison study / 中华外科杂志

<p><b>OBJECTIVE</b>To compare activation and concentration of insulin, and blood glucose control in patients between insulin added into "all in one" bags and syringes at parenteral nutrition (PN).</p><p><b>METHODS</b>From April 2006 to August 2006, 20 consecutive patients after gastrointestinal operations were recruited and randomized to instillation group and pump group. In instillation group, the insulin was directly added into PN and transfused. In pump group, the insulin was added into syringes and transfused by infusion pump. Activation and concentration of insulin, and blood glucose in patients were measured at beginning infusion, infused 1000 ml, infused 2000 ml, and remained 100 ml daily for the first 3 days after operation.</p><p><b>RESULTS</b>There was a tendency of decrease for the activation and concentration of insulin in both groups with the time. There was no significant difference of activation of insulin between the two groups (P = 0.347). There were no significant differences of blood glucoses between the two groups, and between the four time points in each groups (P > 0.05). There were no complications association with blood glucoses in the two groups.</p><p><b>CONCLUSIONS</b>Both of activation and concentration of insulin at PN decreased gradually and slightly with the time no matter the ways of insulin infusion. Activation of insulin and blood glucoses in patients are no significant differences between the two groups. Insulin can be safely added into "all in one" bags at PN.</p>

Pulmonary artery perfusion with hypothermic solution inhibits the apoptosis of lung parenchymal cells during cardiopulmonary bypass / 中华外科杂志

<p><b>OBJECTIVE</b>To study effects of pulmonary artery perfusion with hypothermic solution on the apoptosis of lung parenchymal cells during cardiopulmonary bypass.</p><p><b>METHODS</b>Forty children with tetralogy of Fallot were divided into control group (n = 20) and protective group (n = 20). The patients in control group were performed using routine approaches. Patients' pulmonary artery were infused with 4 degrees C protective solution during cardiopulmonary bypass in protective group. Lung biopsy specimens were obtained after operations in order to study the apoptosis of lung parenchymal cells using tunnel techniques. At same time, patients' pulmonary functions and clinic index were monitored.</p><p><b>RESULTS</b>The rate of apoptosis cells of lung parenchymal cells was (18 +/- 7)% in control group, whereas (10 +/- 2)% in protective group. There was significant difference between both groups (t = -2.95, P < 0.05). Index O(2) in protective group was higher than that in control group at 0, 6 and 12 hours after operations [(492 +/- 172), (444 +/- 104), (489 +/- 58) mm Hg versus (369 +/- 126), (347 +/- 107), (340 +/- 119) mm Hg, t = 2.59, P < 0.05; t = 2.88, P < 0.01; t = 5.06, P < 0.01, respectively)]. The time of mechanical ventilation was significantly shorter in protective group than in control group [(15 +/- 11) hours versus (26 +/- 15) hours, t = -2.76, P < 0.01].</p><p><b>CONCLUSION</b>Pulmonary artery perfusion with hypothermic solution can inhibit the apoptosis of lung parenchymal cells and relieve cardiopulmonary bypass-induced lung injury.</p>

Effects of epimedium total flavonoids phytosomes on preventing and treating bone-loss of ovariectomized rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effects of Epimedium total Flavonoids Phytosomes on preventing and treating bone-loss of the castrate osteoporosis rat model.</p><p><b>METHOD</b>The osteoporosis model was established with 4-month-odl panther's rats, their ovaries on both sides castrated. Dual energy X-ray scanning was used to determine the bone density, and immunity and ELASA were used to assay concentration of estradiol and IL-6 in serum respectively, then determine their effect.</p><p><b>RESULT</b>The BMP and E2 of high dosage group nilestriol group and normal group are higher than those of model group (P < 0.01), while their content of IL-6 is apparently lower than that of model group(P < 0.01).</p><p><b>CONCLUSION</b>The osteoporosis model was established successfully and the using of EFP can improve the bone density, enhance E2 level and decrease the IL-6 concentration in serum.</p>