As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

OBJECTIVETo explore the clinical application of sural neurovascular pedicle fasciocutaneous reversed island flap to repair soft-tissue defection of the ankle and foot.

METHODSFrom Sep. 1994 to Oct. 2004,29 patients with soft-tissue defects in the ankle and foot were repaired by use of sural neurovascular fasciocutaneous reversed island flap, including 15 cases of traumatic defects, 11 cases of burns and 3 cases of chronic ulcer. The flap area ranged from 5 cm x 7 cm to 12 cm x 20 cm, and the length of pedicle from 5 cm to 12 cm.

RESULTSThe flaps survived totally in 27 cases, the distal necrosed partially and secondary free-skin grafting were further conducted in 2 cases. Twenty-one cases were followed-up for 3 to 60 months,the circulation, color and texture of the flaps were excellent and 2-point discrimination was 10 - 15 mm. The appearance and function of ankle joints were good.

CONCLUSIONThis flap has sufficient blood supply and a high survival rate; It is convenient in design, dissection and without sacrifice of major arteries. So, it is an effective method for the reconstruction of soft-tissue defects in ankle and foot.

Adolescent ; Adult ; Ankle Injuries ; surgery ; Female ; Foot Injuries ; surgery ; Humans ; Male ; Middle Aged ; Skin Transplantation ; methods ; Soft Tissue Injuries ; surgery ; Sural Nerve ; blood supply ; Surgical Flaps ; blood supply ; Young Adult

Objective Few studies are reported on the relationship of subclinical hypothyroidism ( SCHT ) with visfatin and endothelin .This study aimed to investigate their relationship in patients with cerebral infarction . Methods A total of 200 cerebral in-farction patients treated in The Second Affiliated Hospital of Hainan Medical University from January 2011 to July 2017 were divided in-to a control ( with normal thyroid function , n=40 ) , a mild SCHT ( with thyroid-stimulating hormone TSH <10 mIU/L, normal free triiodothyronine FT3 and normal free thyroxine FT4, n=60), a se-vere SCHT (with TSH≥10 mIU/L, normal FT3 and normal FT4, n=60) , and a clinical hypothyroidism ( CHT ) group ( with TSH ≥4 mIU/L, decreased FT3 and decreased FT4, n=40).The mild SCHT patients were subdivided into medication group A and non-medication group A, and the severe SCHT patients into medication group B and non-medication group B, 30 in each group, those in the medica-tion groups A and B treated by routine therapy plus oral levothyrocine , and those in the non-medication groups A and B by routine ther-apy only.We recorded the age, gender, body mass index, blood pressure, blood glucose, blood lipid, and thyroid function of the pa-tients, and compared the levels of visfatin and endothelin among different groups . Results The level of visfatin was significantly ele-vated in the severe SCHT and CHT groups as compared with the controls ([46.3±10.1] and [49.5±13.6] vs [40.2±9.7] ng/mL, P<0.05), and so was it in medication group B as compared with non-medication group B at 6 months after treatment ([42.9±6.4] vs [39.3±5.5] ng/mL, P<0.05). Conclusion Visfatin is closely related with thyroid hormone in cerebral infarction patients with se -vere subclinical hypothyroidism .Examination of thyroid function is necessary for cerebral infarction patients for the sake of early detec -tion of severe subclinical hypothyroidism and timely intervention .

OBJECTIVETo discuss the value of pre-operative semen analysis of patients with varicocele as a predictive restore index of sperm motility and fertilizing capacity after varicocelectomy.

METHODSSemen analysis was carried out with computer-aided sperm analyzer in 107 patients with varicocele and all patients were referred to the clinic with diagnosis of male infertility. Stratification of patients as group A (n = 32), B ( n = 36) and C (n = 39) was based on pre-operative total motile sperm count (TMSC). Follow-up included semen analysis and pregnancy data after three months following left or bilateral varicocelectomy.

RESULTSThe average post-operative TMSC increased significantly when compared with the pre-operative. However, a mean absolute increase in group A and B was better than that in group C (P < 0.05). Of the 68 patients in groups A and B based on pre-operative TMSC, 56 patients' TMSC (82.4%) was > or =20 x 10(6) after varicocelectomy, and that of only 8 (20.5%) patients in group C was > or =20 x 10(6) following varicocelectomy. Of the 98 patients wives, 36 had natural conception. Pregnancy rates in groups A and B were higher than that in group C (P < 0.05).

CONCLUSIONVaricocelectomy may be the most effective method to patients with varicocele with pre-operative TMSC > or = 5 x 10(6), but it may be not the best method for patients with severe oligoasthenospermia (pre-operative TMSC < 5 x 10(6)).

Adult ; Female ; Follow-Up Studies ; Humans ; Infertility, Male ; physiopathology ; surgery ; Ligation ; Male ; Pregnancy ; Pregnancy Rate ; Semen ; physiology ; Sperm Count ; Sperm Motility ; Varicocele ; physiopathology ; surgery

Aneurysm, Dissecting/surgery* ; Aorta, Thoracic/surgery* ; Aortic Aneurysm, Thoracic/surgery* ; Blood Vessel Prosthesis Implantation ; Humans ; Treatment Outcome ; Vascular Surgical Procedures

OBJECTIVETo evaluate the effects of rapamycin (RPM)-loaded poly (lactic-co- glycolic) acid (PLGA) nanoparticles (NPs) on the proliferation, distribution of cell cycle, and expression of p27 protein in human umbilical arterial vascular smooth muscle cell (HUASMC) in vitro.

METHODSThe primarily culture model of HUASMC was successfully established by explant-attached method in vitro. The cells were administrated with different doses of RPM, and RPM-PLGA NPs were observed as treat groups compared with PLGA NPs and M231-SMGs medium cultured group. The effect of RPM-PLGA NPs on proliferation of HUASMC was assessed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetry method. The influences of RPM-PLGA NPs on the cell cycle and cellular growth kinetics of HUASMCs were tested by flow cytometry. The effect of RPM-PLGA NPs on the expression of p27 protein of HUASMCs was assessed through an immunohistochemical method.

RESULTSCompared with the control group, the proliferation of HUASMCs was inhibited by 50 microg/L and higher concentration of RPM-PLGA NPs in a dose-dependent manner (P < 0.05). The numbers of cells entering cell cycle of S/G2/M phases were significantly lower in RPM-PLGA NPs and RPM treated groups. Histologically, the expression of p27 were up-regulated in 500 microg/L RPM-PLGA NPs and 100 microg/L RPM treated group (all P < 0.01 ) when compared with the control group.

CONCLUSIONSRPM-PLGA NPs has a similar effects as RPM in inhibiting the growth of in vitro cultured HUASMC. It can remarkably suppress the expression of in vitro cultured HUASMC p27 protein, arrest its cell cycle at G1/S phase, and inhibit its proliferation.

Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Drug Carriers ; Humans ; Lactic Acid ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; Nanoparticles ; Polyglycolic Acid ; Sirolimus ; administration & dosage ; pharmacology ; Umbilical Arteries ; cytology

OBJECTIVETo sought to engineer and characterize a biodegradable nanoparticles (NPs) containing rapamycin which use poly (lactic-co-glycolic) acid (PLGA) as the carrier matrix and to assess its in vivo release characteristics by local drug delivery system intravascularly.

METHODSRapamycin-loaded PLGA NPs were prepared by an emulsification/solvent evaporation technique, and NPs size distribution was assessed by submicro laser defractometer. The particle morphology was observed by scanning electron microscopy. In vitro release from the NPs was performed in TE buffer at 37 degrees C under rotation utilizing double-chamber diffusion cells on a shake stander. In vivo NPs intravascular local delivery were performed by DISPATCH catheter in New Zealand rabbit abdominal aorta and Chinese experimental mini-pigs coronary artery models.

RESULTSBiodegradable rapamycin loaded PLGA NPs were constructed successfully by emulsification solvent-evaporation technique. The diameter of rapamycin-PLGA NPs was around 246.8 nm with very narrow size distribution, and rapamycin-NPs showed good spherical shape with smooth uniform surface. Rapamycin loaded in NPs were around was 19.42%. Encapsulation efficiency of drug was over 77.53%. The in vitro release of rapamycin from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. After a single 10 minutes infusion of rapamycin-PLGA NPs suspension (5 mg/ml) under 20.27 kPa through DISPATCH catherter in vivo, the mean rapamycin levels at 7 day and 14 day were (2.438 +/- 0.439) and (0.529 +/- 0.144) microg/mg of the dry-weight of the artery segments (2 cm) which local delivery were administrated.

CONCLUSIONSPLGA NPs controlled drug delivery system for intraarterial local anti-proliferative drug delivery can potentially improve local drug concentration and prolong drug residence time in animal model in vivo. It should be appropriate for further study of its therapy efficiency in human.

Animals ; Aorta, Abdominal ; drug effects ; Coronary Vessels ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Infusions, Intra-Arterial ; Lactic Acid ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Polyglycolic Acid ; chemistry ; Rabbits ; Sirolimus ; administration & dosage ; pharmacokinetics ; Swine ; Swine, Miniature

The study was to investigate the hemorheologyic changes of group A blood recipient transfused with large amounts of group O whole blood, by erythrocyte count, sympexis index, erythrocyte deformation index, erythrocyte rigid index and whole blood reduced viscosity, 60 ml of group A whole blood were added with 9, 12, 15 and 18 ml of group O whole blood (which corresponds to the 4 000 ml whole blood added with 600, 800, 1 000 and 1 200 ml whole blood). The mixed blood was incubated at 37 degrees C with mixing at 80 times per minute. Samples were taken from the mixed blood at 30 minutes, 2, 4, 8, 12 and 24 hours after culture, and the hemorheology of the mixed whole blood was determined by FASCO-series type 3020B automatic rheograph apparatus. The results showed that there were no differences of erythrocyte count, sympexis index, erythrocyte deformation index, erythrocyte rigid index and whole blood reduced viscosity among all different kinds of mixed whole blood, and there was no difference of sympexis index at different times, but there were obvious differences of erythrocyte count, erythrocyte deformation index, erythrocyte rigid index and whole blood reduced viscosity. It is concluded that blood transfusion of 1,200 ml group O whole blood to a recipient with 50 kg of body weight but with different blood type in emergent situation may exert no harm to the erythrocytes of recipient in a short term.
ABO Blood-Group System ; Blood Group Incompatibility ; blood ; prevention & control ; Blood Transfusion ; Erythrocyte Count ; Erythrocytes ; cytology ; Flow Cytometry ; instrumentation ; methods ; Hemodynamics ; Hemorheology ; Humans

Objective The epidemiological characteristics of congenital heart disease(CHD)among Tibetan children whose age ranged from 4 to 18 at different altitude were investigated in Qinghai province.Methods 32 578 Tibetan children living at 2535 m,3600 m and 4200 m were surveyed with the following 3 steps:prescreened,counterchecked and diagnosed with color Doppler.The entity distribution was then analysed and the age and gender were compared respectively.Resuits 235 CHD cases were identified.The total morbidity was 7.21‰.CHD morbidity was rising with the increase of altitude with 5.45‰ at 2535 m,6.80‰ at 3600 m and 9.79‰ at 4200 m respectively.There were significant static differences between 4200 m and the others with χ2=7.002(P＜0.01)to 2535 m and χ2=5.540(P＜0.05)to 3600 m.However,there was no statistical difference between 2535 m altitude and 3600 m altitude.The morbidity in different age had no statistical difference at 2535 m altitude but statistically increased with the increase of age at 3600 m and 4200 m.The total ratio of 16-18 age was significantly higher than other age periods with χ2=10.79(P＜0.005)to 4-7 age period and with χ2=5.60(P＜0.05)to 8-12 age period.The atrial septal defect(ASD)morbidity rates in three places was 39.1%followed by ventricular septal defect(VSD)with 32.8%and patent duetus arteriosus(PDA)with 24.7%.However,the constitute of CHD was different in different altitudes that VSD with 43.5%at 2535 m.ASD with 42.8%at 3600 m and PDA with 50.8%at 4200 m which was the highest morbidity.Conclusion Morbidity.constitutes and difference in gender and age were related to altitude.

OBJECTIVETo investgate the effects of rapamycin(RPM)and RPM-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(NPs)on the apoptosis of human umbilical arterial vascular smooth muscle cells(HUASMCs)in vitro and expression of bcl-2 and p27(kip1) protein.

METHODSHUASMCs were cultured in vitro and divided to RPM and RPM-PLGA-NPs groups treated at 3 different concentration by 12 and 24 hours,with M231-smooth muscle growth supplements medium and null-PLGA-NPs treated groups as controlled. The apoptosis of HUASMCs was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and flow cytometry. The expressions of bcl-2 and p27(kip1) were detected by streptacidin/peroxidase immunohistochemical method. The effect on cellular proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidecolorimetry.

RESULTSThe proliferation of HUASMCs was inhibited by RPM and RPM-PLGA-NPs in a dose-dependent manner. DNA electrophoresis showed DNA ladder in RPM and RPM-PLGA-NPs groups and classical scalar strips in control groups. The apoptotic indexes of RPM 100 ng/ml group and RPM-PLGA-NPs 500 ng/ml group detected by flow cytometry were(45.45<2.36)% and(35.04<5.64)%,respectively,which were significantly higher than that of M231-smooth muscle growth supplements control group [(2.60<0.95)%,all P<0.01]. The apoptotic indexes of groups incubated with RPM and RPM-PLGA-NPs for 24 hours were significantly higher than those of groups which incubated for 12 hours(P<0.05,P<0.01). The positive expression indexes(PEI)of p27(kip1) and bcl-2 protein were higher in RPM and RPM-PLGA-NPs groups than that of control groups. The Spearman's rank correlation coefficient test showed that there was no significant correlation between the PEI of p27(kip1) and the apoptotic indexes in the RPM group and RPM-PLGA-NPs group(P>0.05).

CONCLUSIONSRapamycin-loaded PLGA nanoparticles and rapamycin have similar effects in inhibiting proliferation and inducing apoptosis;meanwhile,they upregulate the expression of p27(kip1) protein without downregulating the expression of bcl-2 protein in HUASMCs in vitro. RPM-PLGA-NPs has more potent pro-apoptotic effect than equivalent dose of RPM but is not linearly correlated with the p27(kip1) expression level.

Apoptosis ; Cell Proliferation ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p27 ; Humans ; In Situ Nick-End Labeling ; Lactic Acid ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Nanoparticles ; Polyglycolic Acid ; Sirolimus ; Umbilical Arteries