Objective To study the characteristics of pharmacokinetics and pharmacodynamics of insulin dry powder inhalation and its relative bioavailability as compared with subcutaneous injection of regular insulin. Methods In this open,single-center,randomized,two-period,cross-over,euglycemic glucose clamp study,18 healthy volunteers(14 men and 4 women),aged(24.9?1.7)years,with body mass index(20.6?1.2)kg/m~2, received the insulin dry powder inhalatin(80 U)or regular insulin(15 U)subcutaneous administration.The blood samples of this study at 0,20,30,40,50,60,70,80,90,100,110,120,135,150,165,180,195, 210,225,240,270,300,330,360,390,420,450 and 480 rain were taken for serum insulin measurement, meanwhile,glucose infusion rates(GIR)were determined per 5 minutes over a period of 8 hours.Results The C_(max)were(57.9?17.8 vs 114.5?29.7)mU/L(tested vs reference preparation),T_(max)were(46.7?45.6 vs 107.8?33.7)min,GIR_(max)were(3.35?0.98 vs 5.17?1.75)mg?kg~(-1)?min~(-1)and T_(GIRmax)were(88.3?17.0 vs 151.9?34.6)min.The relative bioavailability was(10.26?2.25)%,and the relative bioefficacy was(14.33?7.26)%.Conclusion The study shows that insulin dry powder inhalation is absorbed via lungs and its action sets in earlier than that of the regular insulin injected subcutaneously.These pharmacokinetie and pharmacodynamic data may provide a reliabe guide for further clinical trial.

Finite element analysis (FEA) is broadly used in engineering, it was initially applied to simulate and solve a variety of engineering mechanics, thermal, electromagnetics, and other physical problems. The principle is a collective to be composed by an infinite number of particles, and an unlimited number of degrees of freedom from the continuum approximation. Brekelmas and Ryblcki firstly applied the finite element method to orthopedic biomechanics research in 1972. The first cervical vertebra finite element model was established in 1982 by Hosey. With the computer and software technology advances in the past 20 years, finite element method in cervical spine biomechanics studies is increased and widespread.
Biomechanical Phenomena ; Cervical Vertebrae ; anatomy & histology ; physiology ; Finite Element Analysis ; Humans ; Models, Anatomic ; Models, Biological ; Movement

AIM: To examine the relationship between corneal lymphangiogenesis and hemangiogenesis after keratoplasty.METHODS: Nineteen human corneas were obtained from 19 patients undergoing a second corneal transplantation in Zhongshan Ophthalmic Center in 2005. Blood and lymphatic vessels in human transplanted corneas were identified by lymphatic vessel endothelial receptor(LYVE-1) and platelet endothelial cell adhesion modecule-1(PECAM-1) immunohistochemistry, and double enzyme-histochemistry; then the association of corneal blood vessel counting (BVC) with lymphatic vessel counting (LVC) was examined.RESULTS: Corneal hemangiogenesis was present in 12 cases (63%), and lymphangiogenesis occurred in 5 cases (26%) of human transplanted corneas. In addition, corneal lymphangiogenesis was only present in vascularized corneas. LVC was strongly and positively correlated with BVC(r=0.725;P<0.01).CONCLUSION: Corneal lymphangiogenesis develops after keratoplasty, and strongly associates with hemangiogenesis.

OBJECTIVETo investigate clinical characteristics of posterior cruciate ligament (PCL) injuries.

METHODSTo review all 326 patients with PCL injuries from January 2006 to June 2013 retrospectively, which were grouped according to injury patterns. The survey included the gender, age, sides, duration from injury to surgery, cause of injury and combined injuries. Compare the patient-specific factors between two groups.

RESULTSMale patients were the majority of PCL injuries (73%), and 30 to 50 years old patients accounted for 59%. 62.6% of all patients went for a doctor within one month after trauma. Traffic accidents were the main cause of PCL injuries (59%), especially motorcycle accidents (74.3%). Anterior cruciate ligament (ACL) injuries were the most common combined injuries (46.9%),followed by medial collateral ligament (MCL) (29.8%) and posterolateral corner (PLC) (26.1%). The meniscal tears accounted for 30.4% of total cases. The in-substance PCL injuries (71.5%) were far more than avulsion fractures (28.5%), and the former had more combined injuries than the later (P < 0.05). The causes of injuries were statistically different between two groups (P < 0.05). The prevalence of isolated avulsions was higher than isolated in-substance injuries (P < 0.05).

CONCLUSIONIn the general population, in-substance PCL tears were dominant on PCL injuries. The prevalence of combined injuries was quite high, among which ACL injuries were the most common. Insertion avulsion fractures emerged mainly at the tibial side, which had less combined injuries than those suffered in-substance PCL injuries. The incidence of isolated insertion avulsion fractures was higher than isolated in-substance injuries.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Incidence ; Knee Injuries ; epidemiology ; Male ; Middle Aged ; Posterior Cruciate Ligament ; injuries ; Retrospective Studies ; Young Adult

Metastatic epidural compression of the spinal cord is a significant source of morbidity in patients with systemic cancer. With improvment of oncotheray, survival period in the patients is improving and metastatic cord compression is en- countered increasingly often. Surgical management performed for early circumferential decompression for the spinal cord com- pression with spine instability, and spine reconstruction performed. Patients with radiosensitive tumours without spine instabili- ty, radiotherapy is an effective therapy. Spinal stereotactic radiosurgery and minimally invasive techniques, such as vertebro- plasty and kyphoplasty, percutaneous pedicle screw fixation, radiofrequency ablation are promising options for treatment of cer- tain selected patients with spinal metastases.
Decompression, Surgical ; Humans ; Minimally Invasive Surgical Procedures ; Spinal Cord Compression ; therapy ; Spinal Neoplasms ; secondary ; therapy

Objective To observe the effect of inducible costimulator(ICOS) costimulation pathway blockade in rat limb allografts acute rejection by RNA interference. Methods Twenty-seven cases of modified hind llmb allotransplantation were performed from Wistar to SD rats. The rats were divided into 3 gronps(each n=9): the rejection group not given a special disposal; the control group, consisting of SD rats that received injection of pSilencer 4.1 and Sofast complex by vein post transplantation; and the interference group that received injection of pSilencer 4.1-ICOSshRNA and Sofast complex. On the eighth day posttransplantation, 3 rats were killed to study the pathological changes in each group. The expressions of ICOS gene in vivo were detected by flow cytometry and RT-PCR. The mixed lymphocyte reaction (MLR) was performed and eytokines in blood were measured by ELISA. The rest rats were used to record limb survival time. Results The mean survival time in rats of the rejection and the control groups were(11.34±1.21) and (11.14±1.32) days respectively. In the interference group, the mean survival time of limb allografts was (16.85±1.73) days(P<0.05). The rats in the rejection and the control groups experienced moderate to serious acute rejections with skin epidermal necrosis, a large quantity of lymphocyte infdtration, muscle cell necrosis and interstitial edema, while the pathological changes in rats of the interference group were mild. The splenocyte ICOS mRNA expression level in the interference group(18.75%) was significantly lower than that of the rejection group(100%) and the control group(98.51%). ICOS cell surface expression level as judged by the fluorescence intensity was 45.59±12.87 in the interference group, 103.72±21.76 in the rejection group, and 93.47±29.55 in the control group(F=6.89, P<0.05). In stimulation assays, a one-way mixed lymphocyte reaction stimulation index(SI), with spleen cells from Wistar and Lewis rats, respectively, the rejection group (5.26±0.42,5.18±0.29) and the control group (5.37±0.27,4.93±0.44) had significantly greater reactions than the interference group(2.37±0.35, 4.87±0.36), respectivily(F=7.29, P<0.05; F=6.19, P0.05). In the IFN-γ and IL-4 expression assays, reactions of the interference group (230.17±38.47,160.32±59.13) were lower than those of the rejection group(490.73±51.48,230.67±45.21) and the control group(480.15±43.96, 240.53± 47.36), (F=7.23,6.75, all P<0.01). Conclusions In vivo transfection of pSilencer 4.1-ICOS shRNA interference plasmid can effectively block T-cell co-stimulation pathway, suppress acute rejection, and prolong limb allografts survival.

OBJECTIVETo investigate the effect and mechanism of ghrelin and its synthetic peptide GHRP-6 on gastric motor in mice.

METHODSIn vivo, the dose-dependent effects of ghrelin (20,50,100,200 mug/kg) and GHRP-6 (20,50,100,200 mug/kg) on gastric emptying were measured by intragastric application of phenol red test which was adapted for use in mice. The effects of atropine, NG-nitro-L-arginine methyl ester (L-NAME), and D-Lys(3)-GHRP-6 (GHS-R antagonist) on the gastric motor induced by ghrelin and GHRP-6 (100 mug/kg) were also investigated. In vitro, the effects of ghrelin (0.01,0.1,1.0,10.0 mumol/L) and GHRP-6 (0.01,0.1,1.0,10.0 mumol/L) on spontaneous contraction of mice fundic muscle strips were studied as well.

RESULTSBoth ghrelin (50,100,200 mug/kg) and GHRP-6 (50,100,200 mug/kg) significantly accelerated gastric emptying (P<0.05), but they failed to accelerate gastric emptying in the presence of atropine, L-NAME and D-Lys(3)-GHRP-6 (P<0.05). Ghrelin (0.1, 1.0, 10.0 mumol/L) and GHRP-6 (0.1, 1.0, 10.0 mumol/L) induced significant contraction of fundic muscle strips in concentration-dependent manner (P<0.05), which could be blocked by tetrodotoxin.

CONCLUSIONGhrelin and its synthetic peptide GHRP-6 accelerate gastric emptying perhaps by activating GHS-R of cholinergic excitatory pathways and nitrergic nervous pathways in the enteric nervous system.

Animals ; Female ; Gastric Emptying ; drug effects ; Ghrelin ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Oligopeptides ; pharmacology ; Stomach ; drug effects ; physiology

BACKGROUNDDiabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 (GHRP-6), increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.

METHODSA diabetic guinea pig model was produced by intraperitoneal (i.p.) injection of streptozotocin (STZ, 280 mg/kg). Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 (10 - 100 microg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor (GHS-R) antagonist, D-Lys(3)-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 (100 microg/kg) was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 (0.01 - 10 micromol/L) on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction (RT-PCR).

RESULTSWe established a guinea pig model of delayed gastric emptying. Ghrelin (20, 50, or 100 microg/kg) and GHRP-6 (20, 50, or 100 microg/kg) accelerated gastric emptying in diabetic guinea pigs with gastroparesis (n = 6, P < 0.05). In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 (100 microg/kg) failed to accelerate gastric emptying (n = 6, P < 0.05). D-Lys(3)-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist (n = 6, P < 0.05). Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs (n = 6, P < 0.05). RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.

CONCLUSIONSGhrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.

Animals ; Diabetes Mellitus, Experimental ; complications ; Female ; Gastric Emptying ; drug effects ; Gastroparesis ; drug therapy ; physiopathology ; Ghrelin ; therapeutic use ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Oligopeptides ; therapeutic use ; Receptors, Ghrelin ; analysis ; Streptozocin

Background There is multi-dimensional order of spatial stereopsis perception in human,however,current stereopsis examination is zero-order of position disparity.A multi-dimensional space perception model is very important for the detection of stereoacuity.Objective This study was to screen the deficit of zero-order,first-order,second-order multi-dimensional spatial stereopsis perception in amblyopia and strabismus children and to explore the association of zero-order,first-order,second-order spatial perception deficit.Methods Multidimensional spacial perception was examined in 79 children aged 4-14 years in Beijing Children' s Hospital.Nineteen normal children,19 children with ametropia amblyopia,12 children with anisometropic amblyopia,18 children with strabismus and 11 children with strabismus combined amblyopia were included this study.The random-dot and line spatial stereopsis perception in zero-order,first-order and second-order were examined with a new system of multidimensional space perception screening.Written informed consent was obtained from each subject or custodian before any ocular examination associated with this study.Results Absence of zero-order,first-order,second-order random-dot channel was found in 24 children (24/79,30.4％),18 children (18/79,22.8％) and 24 children (24/79,30.4％) respectively,with an average percentage of 27.9％.Absence of zero-order,first-order,second-order line channel was examined in 37 children (37/79,46.8％),37 children (37/79,46.8％),32 children (32/79,40.5％),with an average percentage of 44.7％.In the children with a deficiency of the zero-order spatial perception,the children who still remained the first-order or/and second-order spatial perception of random-dot accounted for 41.6％ and that of lines accounted for 43.2％.In children without deficiency of zero-order random-dot or lines spatial space perception,deficiency of first-order and/or second-order spatial perception was in 37.5％ children.Various order spatial perception deficiency was seen in children suffering from amblyopia or strabismus compared with normal group(P ＜ 0.05).Conclusions There exists spatial perception deficiency in children with amblyopia or strabismus.The patients with zero-order spatial perception absence partially remain a first-order or/and second-order spatial perception;while the patients with normal zero-order spatial perception might have first-order or second-order spatial perception deficiency.The multi-dimensional space perception model has a directive role for the training of visual information process and the treatment of spatial perceptual learning in children with amblyopia or strabismus.

OBJECTIVETo evaluate the midterm follow-up results of extended release of posterior clearance in total knee arthroplasty.

METHODSA total of 120 patients with knee osteoarthritis were equally randomly assigned to the experimental group and control group, and underwent unilateral TKA from March 2010 to March 2012. In experimental group, there were 21 males and 39 females with an average age of (62.2±10.9) years old. In the control group, there were 25 males and 35 females with an average age of (64.9±11.4) years old. All the patients were performed using the anterior knee approach. During operation, after osteotomy of the tibia and the femoral condyle, extended release of the posterior knee clearance were taken in experimental group, while only the clearance of osteophyte in the posterior condyle were performed in the control group. The KSS scores including knee functional score and knee clinical score,as well as the range of motion (ROM) of patients, were compared between the two groups at midterm follow-up.

RESULTSTotally 49 patients in the experimental group and 54 patients in the control group were followed up, and the median follow-up time was 46 months. The knee functional score of patients in the experimental group was 91.3±3.4, which was better than 86.4±3.9 of patients in the control group; initiative ROM of flexion of patients in the experimental group was (133.2±5.9)°, which was better than (126.9±7.4)° of patients in the control group. There were no significant difference of knee clinical score between 86.9±4.6 of patients in the experimental group and 85.7±5.1 of patients in the control group, and the initiative ROM of extension between (0.5±1.1)° and (0.3±1.2)°.

CONCLUSIONExtended release of the posterior knee clearance contributes to the knee function and initiative flexion ROM during a midterm follow-up and patients benefit.

Aged ; Arthroplasty, Replacement, Knee ; methods ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; physiopathology ; surgery ; Range of Motion, Articular