AIMTo discuss the effect of Pitavastatin on angiogenesis in vivo and its mechanism in Klotho heterozygous deficient mice.

METHODSThe heterozygous deficient Klotho mice (kl +/-) and wild mice (kl +/+) from the same litter were used to establish the animal model of hind-limb ischemia and grouped into control and Pitavastatin group, respectively. Hind-limb blood flow was evaluated using Laser Doppler perfusion imager (LDPI) before treatment and after operation of hind-limbs. The capillaries in muscle of limbs were counted by means of CD-31 labeled immuno-fluorescence. The phosphorylation of Akt (Protein kinase B) in cells was measured by direct immunohistochemical technique. The expression of vascular endothelial growth factors (VEGFs) in muscle of limbs was assessed using Western blotting.

RESULTSAfter treatment of Pitavastatin, the blood flow in ischemic limbs of the Kl +/- and wild mice improved obviously, the ratio of blood flow area in ischemic limb to that in non-ischemic limb increased and the density of capillaries increased in ischemic limbs of the Kl +/- and wild mice. Pitavastatin enhanced the phosphorylation of Akt and the expression of VEGF in ischemic limbs of the Kl +/- and wild mice.

CONCLUSIONPitavastatin has the pro-angiogenesis effect in vivo and the VEGF-p-Akt-NO pathway may be involved in the mechanism of the effect of Pitavastatin.

Angiogenesis Inducing Agents ; pharmacology ; Animals ; Heterozygote ; Ischemia ; Male ; Mice ; Mice, Knockout ; Quinolines ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVEWe investigated the effects of pitavastatin on angiogenesis and perfusion in C3H/He mice with unilateral hind limb ischemia.

METHODSC3H/He mice treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per gavage for 1 week underwent unilateral hind limb ischemia surgery and were treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme histochemical technique, vascular endothelial growth factors (VEGFs) expression in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by chrome dioxide Griess method.

RESULTSLower extremity perfusion was significantly improved in pitavastatin treated mice vs. controls as measured by LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment was associated with significantly increased capillary count [(47 +/- 11) vs. (26 +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho-Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P < 0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P < 0.05) and VEGF protein expression in ischemic limbs were also significantly increased in pitavastatin group than those in control group.

CONCLUSIONSPitavastatin enhances angiogenesis and perfusion in CsH/He mice with limb ischemia.

Animals ; Disease Models, Animal ; Ischemia ; physiopathology ; Lower Extremity ; blood supply ; Male ; Mice ; Mice, Inbred C3H ; Neovascularization, Physiologic ; drug effects ; Nitric Oxide ; blood ; Quinolines ; pharmacology ; Vascular Endothelial Growth Factors ; metabolism

Objective To evaluate the self-treatment effectiveness on patients with ehwnic Keshan disease.Methods Twenty patients with chronic Keshan disease were selected from individuals with Keshan disease in Fuyu County,Heilongjiang Province.They were trained three times every three months of self management including pathogenetic condition education,general guidance,drug therapy,and they also taught how to adiust the doBe of drug according to their illness.Major symptom score,heart rate(HR),ultrasoundcardiogram (UCG)index and cardiac functional grading of these patients at basehne,after 3 months and 6 months of treatment were compared.Results The 20 patients rated their main symptoms score as(15.03 ±6.77)before self- treatrnent,and significantly decreased to(7.25±4.82)and(6.70±4.90)after 3 and 6 months treatment(P<0.01); the heart rate(HR) was (76.40±12.06) beats per minute(bpm)before self-treatment,and dramatically decreased to (69.95±12.63),(67.15±9.76)bpm after 3 and 6 months treatment(P<0.01).As for UCG detecting index,left atrial diameter(Lad)aIld left ventricular end-diastolic diameter(LVEDd)Was(37.85 ±5.23)nun and(52.49± 9.38)mm separately before self-treatment,and notablely decreased to(36.77 ±5.63),(52.15 ±9.24)mm,and (35.29±5.50),(50.81±8.88)mm respectirely after 3 and 6 months of treatment(P<0.01 or<0.05);left ventricuIar ejection fractiOII(LVEF)markedly increased(P<0.05),from(55.15±15.80)%at baseline to(57.35± 12.51)%at 3 months and(60.30±13.42)%at 6 months;there were no significant differences in mitral flow E/A ratio changes before and after treatment(P>0.05);compared with prior to the treatment.cardiac function grading was significantly better aftertreatmentfor 3 months(T=36.0,P<0.05),but not after 6 months(T=17.5,P> 0.05).Conclusions The patients'serf-treatment is effective,which we recommend to uphold and widespread.

OBJECTIVETo assess the effect of oxidative stress in development of acute high altitude response (AHAR) during the process of strong physical work at high altitude and its change after return to lower altitude.

METHODSNinety-six officers and soldiers of rapid entering into high altitude (3 700 m) with strong physical work were analyzed, all subjects were male, aged 18-35 years. According to the symptomatic scores of AHAR were divided into 3 groups: severe AHAR (group A, n = 24), mild AHAR (group B, n = 47) and without AHAR (group C, n = 25). Levels in serum 8-iso prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at higher altitude stayed 50 d and after return to lower altitude (1 500 m) 12 h and 15 d, and 50 healthy volunteers (group D) at 1 500 m altitude served as controll.

RESULTSLevels of serum 8-iso-PGF2alpha and MDA [(9.53 +/- 0.47) microg/L, (8.91 +/- 0.39) micromol/L] were significantly higher in group A than those in group B [(8.34 +/- 0.42) microg/L, (7.31 +/- 0.32) micromol/L] , group C [(7.02 +/- 0.48) microg/L, (6.41 +/- 0.23) micromol/L] and group D [(5.13 +/- 0.56) microg/L, (5.48 +/- 0.33) micromol/L], (all P < 0.01), and serum SOD [(52.08 +/- 3.44) micro/ml] was significantly lower in group A than that in group B [62.27 +/- 2.54) micro/ml], group C [(71.99 +/- 3.35) micro/ml] and group D [(80.78 +/- 3.44) micro/ ml] (all P < 0.01), there were significant differences between group B and C, C and D (all P < 0.01). At altitude 3 700 m 50 d, AHAR scores was positively correlated with serum 8-iso-PGF2alpha and MDA (all P < 0.01), negatively correlated with SOD (P < 0.01). Serum 8-iso-PGF2alpha and MDA were negatively correlated with SOD (all P < 0.01). Levels of serum 8-iso-PGF2alpha and MDA were significantly higher at altitude of 3 700 m 50 d than those at altitude of 1 500 m 12 h,15 d in group D (all P < 0.01), and serum SOD was significantly lower than that at 1 500 m 12 h,15 d in group D (all P < 0.01), there were significantly difference between at 1 500 m 12 h and 15 d (all P < 0.01), there were no difference between at 15 d in group D (all P > 0.05).

CONCLUSIONThe more serious of oxidative stress and oxidative/antioxidative imbalance, the more serious of AHAR, oxidative stress and oxidative/antioxidative imbalance may be involved in the development of AHAR. The changes were obviously improved after return to lower altitude 12 h, and recovered to normal after 15 d.

Adolescent ; Adult ; Altitude ; Altitude Sickness ; physiopathology ; Humans ; Male ; Oxidative Stress ; physiology ; Physical Exertion ; physiology ; Young Adult

OBJECTIVETo explore the strategy of damage control in clinical treatment of multiple injuries headed by cervical spinal cord injury.

METHODSA retrospective analysis was performed in 32 patients. Cervical fractures associated with tetraplegia occurred in 18 patients, traumatic intervertebral disk hernia associated with tetraplegia in 2 patients, and cervical fractures and dislocation associated with tetraplegia in 12 patients. Seventeen cases were combined with craniocerebral injury, 7 combined with pulmonary contusion, multi-fractures of rib or hemopneumothorax, 2 combined with pelvic fracture and other 8 combined with fracture of limbs. The neural function was assessed by the American Spinal Injury Association (ASIA) scale.

RESULTSThirty-one patients were followed up for an average of 14 months. Of them, 10 got complete recovery, 13 obtained improvement of more than one ASIA grade, 8 did not improve, and 1 died.

CONCLUSIONSFor the emergency treatment of multiple injuries headed by cervical spinal cord injury, the damage control strategy is the principle to follow. The final operations are preferably performed within 5 to 10 days after injury so as to raise the successful rate of remedy.

Adolescent ; Adult ; Cervical Vertebrae ; injuries ; Emergency Treatment ; Female ; Humans ; Male ; Middle Aged ; Multiple Trauma ; etiology ; surgery ; Quadriplegia ; Retrospective Studies ; Spinal Cord Injuries ; surgery

Objective In order to investigate etiology and molecular-epidemiological characteristics of enterovirus associated encephalitis (EAE) in Zhejiang,2008-2012.Method Cerebrospinal fluid and stool specimens were collected from suspected EAE patients,who were admitted to our hospitals.RD and Hep-2 cell lines were used to isolate enterovirus (EV).Serotypes of these EV isolates were identified through neutralization test by using serotype specific anti-sera.VP 1 genes of these isolates were sequenced,compared and used for the construction of phylogenetic tree.Results 127 (20.6％) human enterovirus (HEV) strains were isolated from 616 samples,which were collected from 610 patients.Serotypes of these EV isolates,including 60 coxsackievirus (CV),and 67 Echovirus (E) appeared to be CVA9,CVB1,CVB3-5,E3,E4,E6,E9,El4,E25 and E30,respectively.Predominant EV serotypes on EAE from 2008 to 2012 were seen as CVB3,CVB5,E6,E30 and E30,respectively.The full length of VP1 genes from different EV isolates was between 834 and 918 nucleotides.The VP1 gene similarities between these isolates and the reference strains were from 76.7％ to 85.0％ (nucleotides level) and 91.1％ to 97.9％ (amino acids level).The VP1 genes from E6 serotype isolates appeared most diverged,reaching 20.4％ (nucleotides level) attd 4.8％ (amino acids level).Based on the generated phylogenetic tree,all the EV isolates were fallen on the same branch of HEV-B,and the isolates in the same serotype formed one sub-branch,suggesting there existed geographical and temporal effects.E6 isolates diverged into two branchlets.Conclusion EVs from HEV-B were the etiologic agents for EAE in Zhejiang province from 2008 to 2012.All these EV isolates showed 12 serotypes,with predominant isolates varied every year.E30 was determined as the most dominant serotype while serotype E6 diverged into two sub-genetypes.

Objective:To forecast the reduce of medical direct expenses of China from 2016 to 2020,under the circumstances that some outpatients and inpatients of tertiary hospitals and secondary hospitals could be distributed to primary medical institutions.Methods:According to the number of outpatients,number of inpatients,medical expenses of outpatients per visit,and medical expenses of inpatients per visit in the first grade,second grade and third grade public hospitals from 2006 to 2015,the corresponding visit numbers and costs from 2016 to 2020 were forecasted based on liner regression model.The percentages of transferable patients out of all patients in different levels of institutions could be equal to 10％,20％ and 30％.The direct medical expense could be saved after the distribution were calculated.Results:If the trend of health service utilization from 2016 to 2020 were equal to the sample,the third grade hospitals would keep the fast increasing of outpatient expenses and patients.8％,16％ and 24％ of the total expenses would be saved if 10％,20％ and 30％ patients in third and second were led to the second and first grade medical institutions.Conclusion:It needed to slowdown the increasing trend of medical expenses,lead patients visit hospitals reasonably,strengthen the construction capacity of second grade medical and health institutions,meanwhile,the medical and health service system construction should adjust the distribution ratio.

The glymphatic system is a cerebrospinal fluid-interstitial fluid exchange system dependent on the water channel aquaporin-4 polarized on astrocyte endfeet, which is proposed to account for the clearance of abnormal proteins (e.g. β-amyloid) and metabolites (e.g. lactate) from the brain. Accumulating studies have revealed that glymphatic activity during sleep and general anesthesia is dramatically enhanced, while its function is significantly damaged during aging, traumatic brain injury, Alzheimer's disease, stroke, and diabetes. The glymphatic hypothesis is a breakthrough in the field of neuroscience recently, which would considerably enhance our comprehension on the cerebrospinal fluid circulation and its role in the maintenance of brain homeostasis. In this review, we briefly introduced the conceptualization of glymphatic system, summarized the recent progresses, and prospected its future investigation and potential clinical application.

Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine (TMP), one of the most widely used medicinal compound isolated from traditional Chinese herb, is usually employed for anti-oxidation, anti-inflammation, anti-platelet aggregation, anti-lipid, anti-fibrosis, as well as activating blood, removing stasis, dilating small arteries, improving microcirculation and antagonizing calcium. In the present paper, the anti-adhesion effect of TMP were reviewed. TMP was found to play a multi-target and muti-link role in anti-adhesion by inhibiting hyperplasia of collagen and overexpression of adhesion-related factors and reducing the concentration of white blood cells and fibrin in plasma. Because previous studies mostly focused on in vitro experiments and animal experiments, there is an urgent need for clinical research with abundant indicators to further prove its anti-adhesion potency. Future basic research should concentrate on the development of TMP as a biological material.