Objective To investigate the characteristic of the expression of facilitative glucose transporter 1 (Glut1) in bronchial aveolar carcinoma (BAC) and the relationship between expression of Glutl and fluorine-18 fluorodeoxyglucose (18F-FDG) uptake. Methods Twenty patients with BAC were imaged with 18F-FDG positron emission tomography (PET) before surgery. Maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean ) of tumor and standard uptake value of normal lung (SUVIung) were measured. The expression of Glutl was studied in paraffin sections by streptavidin peroxidase (SP) immunohistochemistry. Results All tumors of the patients could be detected by ^18F-FDG-PET. 18F-FDG uptake of tumor was higher than that of normal lung (SUV SUV and SUVlong were 3.09± 1.35, 2.37±1.03 and 0.39±0.09 respectively). The expression of Glutl were positive in all tumors (73. 8%± 14. 8% of positive cell rate, 2. 8 ± 0. 9 grade of staining intensity). Predominantly cytoplasm positive with weak staining intensity were observed in many tumors. Glutl negtive were observed in normal bronchial and lung parenchyma. Positive correlations were found among 18F-FDG uptake, Glut1 expression and tumor size (P〈0. 01). Conclusion Glutl expression with peculiarity in BAC is correlate with 18F-FDG uptake.
ObjectiveTo investigate the effects of dipyridamole (DP), one of the human equilibrative nucleoside transporters (hENTs) blockers, on 5-fluorouracil (5-FU) induced cell apoptosis and cell cycle changes of the pancreatic cancer Panc-1 cell line. MethodsPancreatic cancer cell line Panc-1 was divided into hENTs blocked group and hENTs unblocked group. The hENTs blocked group was further divided into two subgroups according to the DP concentration, 5 μmol/L DP group and 10 μmol/L DP group. Each group was incubated in culture medium with or without 1.5×106 ng/L 5-FU for 24 h. Cell apoptosis and cell cycle were detected by flow cytometry. Results①The apoptosis results of each group: Incubated in culture medium with 1.5×106 ng/L 5-FU for 24 h, the apoptosis rates of 5 μmol/L DP group and 10 μmol/L DP group were higer than those of hENTs unblocked group (Plt;0.05), and which of 10 μmol/L DP group was higer than that of 5 μmol/L DP group (Plt;0.05). Incubated in culture medium without 5-FU for 24 h, there were no significant differences of the apoptosis rates among three groups (Pgt;0.05). ②The cell cycle results of each group: Incubated in culture medium with 1.5×106 ng/L 5-FU for 24 h, the percentages of S phase cells in the 5 μmol/L DP group and 10 μmol/L DP group were less than those of hENTs unblocked group (Plt;0.05). The percentage of S phase cell of 5 μmol/L DP group reduced to 87.09% and that of 10 μmol/L DP group reduced to 74.06% as compared with hENTs unblocked group. 5-FU had little influence on G2 phase (Pgt;0.05) except for the percentage of G2 phase cells in the 5 μmol/L DP group increased significantly (Plt;0.05) as compared with the hENTs unblocked group. Incubated in culture medium without 5-FU for 24 h, there were no significant differences of the cell cycles among three groups (Pgt;0.05). ConclusionsIn pancreatic cancer Panc-1 cell, DP could enhance the cytotoxicity of 5-FU by blocking hENTs. The enhanced cytotoxicity is related to elevation of 5-FU concentration in cells, and unrelated to DP itself.
Sports-related traumatic brain injury (srTBI) is a traumatic brain injury (TBI) caused by sports, which can result in cognitive and motor dysfunction. Currently, research on the molecular mechanism of srTBI and related drug development mainly relies on monolayer culture models and animal models. However, many differences exist in cell populations and inflammatory responses between these models and human pathophysiological processes. Most of the researches derived from the models can’t effectively conducted translational research. Emerging three-dimensional (3D) in vitro models bridge the limitations of traditional models in simulating the pathophysiological processes of human srTBI and provide new means to understand srTBI. A literature has reported the research progress of emerging 3D in vitro models in neurological diseases, but there is a lack of systematic summary of the mentioned models in srTBI studies. Here, we review the research progress of emerging 3D in vitro models of srTBI, discuss the advantages and limitations of existing models, and further prospect the future trend of srTBI models. This paper aims to provide a new research perspective for researchers in tissue engineering and sports medicine to study the molecular mechanisms of srTBI and develop neuroprotective drugs.
Objective To elucidate whether glucose transporters-4 (GLUT-4) takes part in glucose uptake of mesenchymal stem cells (MSCs) and whether Akt gene improves translocation and expression of GLUT-4 in MSCs under hypoxic environment ex vivo. Methods MSCs, transfected by Akt gene and no, were cultured with normoxia (5% CO2) or hypoxia (94%N2, 1%O2 and 5% CO2) at 37 ℃ for 8 h. Glucose uptake was assayed by using radiation isotope 2-[3H]-deoxy-Dglucose (3H-G) and the expression of GLUT-4 protein and mRNA was assayed by immunocytochemistry, Western blot and RT-PCR, respectively. Results ①3 H-G intake of MSCs was significantly increased in hypoxiatransfection group than that in hypoxia-non-transfection 〔(1.39±0.13) fold, P<0.05〕, but which was lower than that in normoxia-non-transfection group, P<0.05. ②GLUT-4 was expressed by MSCs under any conditions. Compared with normoxia-non-transfection group, hypoxia decreased the expressions of GLUT-4 mRNA and protein significantly (P<0.05). ③Compared with hypoxianontransfection group, the expression of GLUT-4 〔mRNA(1.756±0.152) fold, total protein in cell (1.653±0.312) fold, protein in plasma membrane (2.041±0.258) fold〕 was increased in hypoxia-transfection group significantly (P<0.05), but which was lower than that in normoxianontransfection group (P<0.05). ④There was significantly positive relation between 3H-G intake and GLUT-4 protein expression in plasma membrane (r=0.415, P=0.001).Conclusion GLUT-4 may take part in glucose uptake of MSCs, and the capability of Akt gene to improve MSCs anti-hypoxia may be finished by its role in increasing the expression and translocation of GLUT-4.
Objective To validate the different expressions of human fxyd6 gene between normal bile duct tissues and malignant tumor tissues, and to observe the subcellular localization of human fxyd6 gene in human cholangiocarcinoma cells. MethodsThe different expressions between normal bile duct tissues and malignant tumor tissues were identified by RT-PCR. In situ polymerase chain reaction (IS-RT-PCR) was applied to detect the subcellular localization of fxyd6 gene in paraffin sections of human cholangiocarcinoma cells. Image analysis software was used to semiquantitatively determine the difference between normal and malignant tissues. ResultsHuman fxyd6 gene was highly expressed in cholangiocarcinoma tissues and lowly expressed in normal ones. There was a significant difference between the expressions of carcinoma cells and normal cells (P<0.05). IS-RT-PCR showed that fxyd6 gene localized in the kytoplasma of epithelial cells of human cholangiocarcinoma. ConclusionHuman fxyd6 gene may act as an essential component of the malignant transformation process in human cholangiocarcinoma.
Sodium-glucose cotransporter (SGLT) -2 inhibitors is a new type of oral sugar-lowering drug. Instead of relying on insulin, it lowers blood sugar by inhibiting the reabsorption of near-curvy tube glucose, which is drained from the urine. SGLT-2 inhibitors not only have a sugar-lowering effect, but also benefit significantly in cardiovascular disease, and this drug has the advantages of permeable diuretic, reducing capacity load, and improving ventricular remodeling. SGLT-2 inhibitors can improve the diastolic function of patients with heart failure with preserved ejection fraction (HFpEF) and reduce the risk of adverse cardiovascular events. SGLT-2 inhibitors can benefit patients with HFpEF. Therefore, this article will discuss the progress of SGLT-2 inhibitors in HFpEF.
ObjectiveTo compare the effectiveness using bone transport and bone shortening-lengthening by Ilizarov technique for tibial bone and soft tissue defects. MethodsBetween January 2004 and May 2012,31 patients with tibial bone and soft tissue defects were managed by Ilizarov technique,the clinical data were retrospectively analyzed.Bone transport was used in 18 cases (group A),and bone shortening-lengthening in 13 cases (group B).There was no significant difference in age,gender,type of fracture,defect location,size of bone and soft defects,and time from injury to operation between 2 groups (P>0.05).Postoperative complications were observed;Paley's criterion was used to assess the bone healing and function recovery of the limb. ResultsAll the flaps survived and healing of wounds by second intention was obtained in all cases of group A;healing of wounds by first intention was obtained in 1 case,delayed healing in 3 cases,and healing by second intention in 9 cases in group B.All patients were followed up 1.5-4.5 years (mean,2.4 years).Pin loosening or pin tract infection occurred in 15 cases of group A and in 10 cases of group B,and limb length discrepancy in 1 case of group B;there was no significant difference in the rate of complication (χ2=0.003,P=0.955).In the distracted zone,all fractures healed naturally with excellent scale.The healing time was (251±39) days in group A,and was (239±45) days in group B,showing no significant difference (t=0.800,P=0.430);the healing index was (4.26±0.19) d/mm in group A,and was (4.13±0.19) d/mm in group B,showing no significant difference (t=1.775,P=0.086).In the bone defect zone,natural healing was obtained in 12 cases and healing after second operation or bone grafting in 6 cases,with healing time of (341±55) days (excellent in 17 cases and good in 1 case) in group A;natural healing was obtained in 11 cases and healing after second operation or bone grafting in 2 cases,with the healing time of (295±62) days (excellent in 12 cases and good in 1 case) in group B;and there was significant difference in the healing time (t=2.195,P=0.036),but no significant difference in the healing scale (Z=-1.693,P=0.091).At last follow-up,the function recovery was excellent in 7 cases,good in 6 cases,and fair in 5 cases in group A,and was excellent in 3 cases,good in 6 cases,and fair in 4 cases in group B,showing no significant difference (Z=-0.660,P=0.509). ConclusionUsing bone transport or bone shortening-lengthening by Ilizarov technique for tibial bone and soft tissue defects,the overall outcomes are similar,but the healing of bone defect zone is faster when using bone shortening-lengthening.
ObjectiveTo systematically review the association between the insertion/deletion (I/D) polymorphism of angiotension-converting enzyme (ACE) gene and the athletes' performance in endurance sports. MethodsDatabases including PubMed, EMbase, CNKI, CBM, VIP, and WanFang Data were searched up to August 1st, 2015 to collect case-control studies about the association between ACE I/D polymorphism and the athletes' performance in endurance sports. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsA total of 37 case-control studies involving 3 032 athletes and 10 857 controls were included. The results of meta-analysis showed that significant association was found between ACE I/D polymorphism and the athletes' performance in endurance sports (DD+DI vs. Ⅱ: OR=0.75, 95%CI 0.67 to 0.83, P<0.01; DD vs. Ⅱ: OR=0.73, 95%CI 0.61 to 0.87, P<0.01; DI vs. Ⅱ: OR=0.74, 95%CI 0.66 to 0.83, P<0.01; D vs. Ⅰ: OR=0.85, 95%CI 0.77 to 0.94, P<0.01). Specifically, the ACE I/D polymorphism was significantly associated with the performance of male athletes in endurance sports (DD+DI vs. Ⅱ: OR=0.73, 95%CI 0.61 to 0.88, P<0.01; DD vs. Ⅱ: OR=0.75, 95%CI 0.60 to 0.93, P=0.01; DI vs. Ⅱ: OR=0.70, 95%CI 0.60 to 0.93, P<0.01; D vs. Ⅰ: OR=0.87, 95%CI 0.77 to 0.97, P=0.01). Subgroup analysis of ethnicity showed that, in Caucasians, except for genetic model DD vs. DI+Ⅱ, the other 4 genetic models were significantly associated with the athletes' performance in endurance sports (DD+DI vs. Ⅱ: OR=0.74, 95%CI 0.65 to 0.84, P<0.01; DD vs. Ⅱ: OR=0.72, 95%CI 0.58 to 0.90, P<0.01; DI vs. Ⅱ: OR=0.73, 95%CI 0.64 to 0.84, P<0.01; D vs. Ⅰ: OR=0.87, 95%CI 0.81 to 0.94, P<0.01); in Africans, significant associations with the athletes' performance in endurance sports were found in genetic model DD vs. DI+Ⅱ (OR=0.75, 95%CI 0.57 to 0.98, P=0.04), genetic model DD vs. Ⅱ (OR=0.62, 95%CI 0.42 to 0.92, P=0.02), and genetic model D vs. Ⅰ (OR=0.80, 95%CI 0.66 to 0.96, P=0.02); in Asians, no significant association was found between ACE I/D polymorphism and the performance of athletes of difference races in endurance sports. ConclusionCurrent evidence indicates that the ACE I/D polymorphism may be associated with the performance of athletes especially male athletes and the Caucasian subgroup in endurance sports. ACE allele D is negatively associated with the athletes' performance in endurance sports, while allele I is positively associated with the athletes' performance in endurance sports. Due to the quality limitations of included studies, more high quality case-control or cohort studies are needed to verify the above conclusions.
ObjectiveTo summarize the effectiveness and experience of Wanger grade 3-5 diabetic foot treated with vacuum sealing drainage (VSD) combined with transverse tibial bone transport.MethodsBetween March 2015 and January 2018, 21 patients with refractory diabetic foot who failed conservative treatment were treated with VSD combined with transverse tibial bone transport. There were 15 males and 6 females, aged 55-88 years (mean, 65 years). The diabetes history was 8-15 years (mean, 12.2 years). The duration of diabetic foot ranged from 7 to 84 days (mean, 35.3 days). The size of diabetic foot ulcer before operation ranged from 2 cm×2 cm to 8 cm×5 cm. According to Wanger classification, 8 cases were rated as grade 3, 11 cases as grade 4, and 2 cases as grade 5. Among the 21 cases, angiography of lower extremity before operation was performed in 5 cases, CT angiography of lower extremity in 16 cases, all of which indicated that the arteries below the knee were narrowed to varying degrees and not completely blocked. Preoperative foot skin temperature was (29.28±0.77)℃, C-reactive protein was (38.03±31.23) mg/L, leukocyte count was (9.44±2.21)×109/L, and the visual analogue scale (VAS) score was 6.8±1.5, and ability of daily living (Barthel index) was 54.3±10.3.ResultsAfter operation, 2 patients with Wanger grade 4 and smoking history failed treatment and had an major amputation (amputation above ankle joint) at 30 days and 45 days after operation, respectively. One patient with Wanger grade 5 and chronic heart failure died of cardiac arrest at 60 days after operation. The remaining 18 patients were followed up 6-24 months (mean, 9.2 months). The external fixator was removed at 40-62 days after operation, with an average of 46 days. All the wounds healed, with a healing time of 50-120 days (mean, 62.5 days). The pain of 18 patients’ feet was relieved obviously, and there was no recurrence of ulcer in situ or other parts. There was no complication such as tibial fracture and ischemic necrosis of lower leg skin after operation. After ulcer healing, the foot skin temperature was (30.86±0.80)℃, C-reactive protein was (22.90±18.42) mg/L, VAS score was 2.4±1.2, and Barthel index was 77.3±4.6, all showing significant differences when compared with preoperative ones (P<0.05); the leukocyte count was (8.91±1.72)×109/L, showing no significant difference (t=1.090, P=0.291).ConclusionVSD combined with transverse tibial bone transport can effectively promote the healing of Wanger grade 3-5 diabetic foot wounds, but smokers, unstable blood glucose control, and chronic heart failure patients have the risk of failure.
ObjectiveTo evaluate the effectiveness of Ilizarov technique-based transverse tibial bone transport on the treatment of severe diabetic foot ulcer (Wagner grades 3 to 5) complicated with systemic inflammatory response syndrome (SIRS).MethodsBetween August 2014 and December 2017, 33 patients with severe diabetic foot and SIRS were treated with Ilizarov technique-based transverse tibial bone transport. There were 27 males and 6 females, with a mean age of 60.6 years (range, 34-79 years). All of them suffered from type 2 diabetes mellitus. The duration of diabetes was 1-28 years (mean, 10 years) and the duration of diabetic foot was 1-12 months (mean, 2.7 months). According to Wagner classification, there were 8 cases in grade 3, 23 cases in grade 4, and 2 cases in grade 5. The wound healing condition was observed after operation, and the limb salvage rate was calculated. The changes in body temperature, heart rate, respiratory rate, white blood cell count, erythrocyte sedimentation rate, and C-reactive protein concentration were assessed. The skin temperature of the dorsum of the foot was measured, and the visual analogue scale (VAS) score was used to evaluate the improvement of foot pain.ResultsAll 33 patients were followed up 3-30 months (mean, 14.1 months). All ulcers healed and the healing time was 3-12 months (mean, 5.3 months); the limb salvage rate was 100%. Postoperative body temperature, heart rate, respiratory rate, white blood cell count, erythrocyte sedimentation rate, and C-reactive protein concentration were significantly lower than those before operation (P<0.05). The skin temperature of the dorsum of the foot was (32.64±2.17)℃ at 1 month after operation, which was significantly improved when compared with preoperative value [(31.28±1.99)℃] (t=0.05, P=0.00); but there was no significant difference in skin temperature compared with healthy side [(32.46±2.10)℃] (t=2.04, P=0.41). The VAS score was 2.4±0.7 at 1 month after operation, which was significantly improved when compared with preoperative score (4.3±0.8) (t=3.10, P=0.00).ConclusionIlizarov technique-based transverse tibial bone transport is an effective way to treat severe diabetic foot complicated with SIRS. It can promote foot ulcer healing and avoid amputations.