To investigate the effects of 2-(4-methoxycarbonyl-2-tetradecyloxyphenyl)carbamoylbenzoic acid (CX09040) on protecting pancreatic β cells, the β cell dysfunction model mice were induced by injection of alloxan into the caudal vein of ICR mice, and were treated with compound CX09040. Liraglutide was used as the positive control drug. The amount and the size of islets observed in pathological sections were calculated to evaluate the β cell mass; the glucose stimulated insulin secretion (GSIS) test was applied to estimate the β cell secretary function; the oral glucose tolerance test (OGTT) was taken to observe the glucose metabolism in mice; the expressions of protein in pancreas were detected by Western blotting. The effects on the target protein tyrosine phosphatase 1B (PTP1B) were assessed by the PTP1B activities of both recombinant protein and the intracellular enzyme, and by the PTP1B expression in the pancreas of mice, separately. As the results, with the treatment of CX09040 in alloxan-induced β cell dysfunction mice, the islet amount (P<0.05) and size (P<0.05) increased significantly, the changes of serum insulin in GSIS (P<0.01) and the values of acute insulin response (AIR, P<0.01) were enhanced, compared to those in model group; the impaired glucose tolerance was also ameliorated by CX09040 with the decrease of the values of area under curve (AUC, P<0.01). The activation of the signaling pathways related to β cell proliferation was enhanced by increasing the levels of p-Akt/Akt (P<0.01), p-FoxO1/FoxOl (P<0.001) and PDX-1 (P<0.01). The effects of CX09040 on PTP1B were observed by inhibiting the recombinant hPTP1B activity with IC50 value of 2.78x 10(-7) mol.L-1, reducing the intracellular PTP1B activity of 72.8% (P<0.001), suppressing the PTP1B expression (P<0.001) and up-regulating p-IRβ/IRβ (P<0.01) in pancreas of the β cell dysfunction mice, separately. In conclusion, compound CX09040 showed significant protection effects against the dysfunction of β cell of mice by enlarging the pancreatic β cell mass and increasing the glucose-induced insulin secretion; its major mechanism may be the inhibition on target PTP1B and the succedent up-regulation of β cell proliferation.
Alloxan ; Animals ; Benzoates ; pharmacology ; Biological Assay ; Disease Models, Animal ; Glucose ; metabolism ; Glucose Tolerance Test ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Liraglutide ; pharmacology ; Mice ; Mice, Inbred ICR ; Molecular Weight ; Pancreas ; drug effects ; enzymology ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; Signal Transduction

OBJECTIVETo explore the role of metabolism of fatty substance and osteoclast activity during the process of steroid-induced necrosis of femoral head through mice model inducing and model index measurement.

METHODSForty SD male mice were divided into 2 groups randomly, the control group and the experiment group. After the gluteal injection of colibacillus endotoxin,the experiment group was given gluteal injection of prednisolone acetate 35.5 mg/kg per week, and 2 ml of normal saline to the control group. The mice were killed 12 weeks later and tested the content of Trap-5b, TC and TG of the blood serum. Vitodynamics, bone density were measured and sections of HE staining, Ca2+ and TRACP staining was made then statistic analysis was performanced.

RESULTSThe content of TC, TG and Trap-5b increased apparently (P < 0.01). Large amount of osteoclasts were found in local medullary cavity. There was severe bone loss and decrease of vitodynamics in subchondral bone (P < 0.01) in experiment group.

CONCLUSIONMetabolic disorder of fatty substance is the key pathogenesis of steroid-induced avascular necrosis of femoral head. Decrease of vitodynamics in subchondral bone due to hyperactivity and increase of osteoclast lead to collapse of femoral head directly.

Animals ; Bone Density ; Disease Models, Animal ; Fatty Acids ; metabolism ; Femur Head Necrosis ; metabolism ; physiopathology ; Humans ; Male ; Osteoclasts ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Steroids ; pharmacology

OBJECTIVETo observe the gene and protein expression of herpes simplex virus type I-thymidine kinase (HSV(1)-tk) in the ovarian tumor tissues and other organs after arterial infusion of HSV(1)-tk gene mediated by GE7 delivery system.

METHODSGE7-polylysine/pCMV-HSV(1)-tk/polylysine-HA20 complexes were constructed. Nine rats with induced ovarian tumor were divided into 3 groups, injecting the 4-element complexes or saline buffer through the ovarian artery and complexes through the tail vein, respectively. The ovarian tumors, hearts, livers, spleens, lungs and kidneys were obtained at 72 hours after injection. RT-PCR and Western Blot were preceeded to determine the expression of HSV(1)-tk gene and protein in the tumor tissues and other organs.

RESULTSIn the group of arterial injection with 4-element complexes, the HSV(1)-tk gene and protein were expressed strongly in the tumor tissues, while little or none was detected in other organs. In the group of arterial injection with saline buffer, no HSV(1)-tk gene and protein was detected in both tumor tissues and other organs. In the group of tail vein injection, none was detected in tumor tissues and only little was found in the livers, spleens, lungs and kidneys.

CONCLUSIONHigh target and gene transfer rates can be obtained when HSV(1)-tk gene is transferred via the artery route mediated by GE7 delivery system. HSV(1)-tk protein can be expressed after the gene transfer. The results may provide a new strategy for target killing of HSV(1)-tk/GCV system in ovarian tumors.

9,10-Dimethyl-1,2-benzanthracene ; Adenocarcinoma ; chemically induced ; genetics ; metabolism ; Animals ; Female ; Gene Transfer Techniques ; Herpesvirus 1, Human ; genetics ; Infusions, Intra-Arterial ; Ovarian Neoplasms ; chemically induced ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Thymidine Kinase ; biosynthesis ; genetics

To approach the effect of CCAAT/enhancer binding proteins (C/EBPs) on un-terminal differentiation of HL-60 cells after treatment with Arsenic Trioxide ( As_2O_3) . Methods The changes of cell morphology were observed by Wright staining, the alteration in the cell proliferation was determined by WST1 experiment and the NBT reduction assay was used to detect the differentiation condition of cells, determination and analysis cell cycle. The expressions of C/EBP? and C/EBP? mRNA in HL-60 cells exposed to ATRA and As_2O_3 were assayed by semi-quantitative RT-PCR. Results It was found that ATRA could up- regulate the mRNA expression of C/EBP? obviously, but down-regulate the mRNA expression of C/EBP?. As_2O_3 could up-regulate the mRNA expression of C/EBP? lightly, down-regulate the expression of C/EBP?. Conclusion Both of ATRA and As_2O_3 can down-regulate the mRNA expression of C/EBP?,but there is no significant difference between these two groups,ATRA and As2O3 can up- regulate the mRNA expression of C/EBP?, with significant differences (P

DNA barcoding is a rapidly developing frontier technology in the world and will be useful in promoting the quality control and standardization of traditional Chinese medicine. Until now, many studies concerning DNA barcoding have focused on leaf samples but rarely on Chinese herbal medicine. There are three issues involved in DNA barcoding for traditional Chinese medicinal materials: (1) the extraction methods for total DNA of the rhizomes of the medicinal materials; (2) intra-specific variation among samples from different places of origin; (3) accuracy and stability of this method. In this study, Gentianae Macrophyllae Radix was used to verify the stability and accuracy of DNA barcoding technology. Five regions (ITS2, psbA-trnH, matK, rbcL, and ITS) were tested for their ability to identify 86 samples of Gentianae Macrophyllae Radix and their adulterants. After improving the DNA extraction method, genomic DNA from all samples was successfully obtained. To evaluate each barcode's utility for species authentication, PCR amplification efficiency, genetic divergence, and species authentication were assessed. Among all tested regions only ITS2 locus showed 100% of PCR amplification and identification efficiencies. Based on the established method, we successfully identified two samples of Gentianae Macrophyllae Radix bought in pharmacy to the original species.
DNA Barcoding, Taxonomic ; methods ; DNA, Plant ; analysis ; genetics ; Drug Contamination ; Genetic Variation ; Genome, Plant ; Gentiana ; classification ; genetics ; Plant Roots ; genetics ; Plants, Medicinal ; genetics ; Polymerase Chain Reaction ; methods ; Quality Control ; Sequence Analysis, DNA ; Species Specificity

BACKGROUNDThis study aimed to evaluate the effects of standard rescue procedure (SRP) in improving severe trauma treatments in China.

METHODSThis study was conducted in 12 hospitals located in geographically and industrially different cities in China. A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment. A regional network (system) efficiently integrating prehospital rescue, emergency room treatments, and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments. Treatment outcomes were compared between before and 1 year after the implementation of the SRP.

RESULTSThe outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP. Implementation of the SRP led to efficient cooperation and information sharing of different treatment services. The emergency response time, prehospital transit time, emergency rescue time, consultation call time, and mortality rate of patients were 24.24 ± 4.32 min, 45.69 ± 3.89 min, 6.38 ± 1.05 min, 17.53 ± 0.72 min, and 33.82% ± 3.87% (n = 441), respectively, before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min, 22.39 ± 4.32 min, 3.26 ± 0.89 min, 3.45 ± 0.45 min, and 20.49% ± 3.11%, separately (n = 495, P < 0.05) after that.

CONCLUSIONSStaff training and SRP can significantly improve the efficiency of severe trauma treatments in China.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Emergency Medical Services ; standards ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Wounds and Injuries ; Young Adult

Aim To investigate whether resveratrol (Resveratrol, Res) induces cardiomyocyte protection by increasing intracellular zinc ion and its possible signal mechanism. Methods H9c2 cells were routinely cultured and 2-deoxyglucose (2-DG) was used to establish an endoplasmic reticulum stress (ERS) model. The experiment was randomly divided into control group, 2-DG group, Res +2-DG group, TPEN + Res + 2-DG group and 3-MA + Res +2-DG group. Cell viability was detected by MTT and CCK-8; the expression levels of ERS molecular chaperone proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) and autophagy proteins LC3 II / I, p62 and p-AMPK were detected by Western blot; the expression of LC3 protein was measured by cellular immunofluorescence; the mitochondrial membrane potential (Aijjm) and the intracellular zinc ion level were measured by laser scanning confocal microscope. Results Compared with the control group, 2-DG reduced cell activity and resveratrol inhibited the changes caused by 2-DG, which was reversed by zinc chelator TPEN. 2-DG increased GRP78 and GRP94 expression and resveratrol inhibited the protein changes caused by 2-DG, which was reversed by TPEN. 2-DG increased the expression of LC3 II / I, p-AMPK and decreased the expression of p62, and resveratrol promoted the effect of 2-DG. 2-DG increased the fluorescence intensity of LC3, and resveratrol enhanced the effect of 2-DG, which was reversed by TPEN and 3-MA. 2-DG reduced the red fluorescence intensity of mitochondrial TMRE and green fluorescence intensity of intracellular zinc ions, and resveratrol inhibited these changes caused by 2-DG, which was also reversed by TPEN and 3-MA. The above differences were all statistically significant (P < 0. 05). Conclusion Resveratrol increases intracellular zinc to promote ERS-induced autophagy and prevent the mPTP opening in H9c2 cardiac cells.

Objective: To explore the effects of bicycle ergometer rehabilitation training on quadriceps and walking ability of patients with lower limb dysfunction caused by extensive burns. Methods: A prospective randomized controlled study was conducted. A total of 40 patients with extensive burns who met the inclusion criteria and were admitted to Tongren Hospital of Wuhan University＆Wuhan Third Hospital from December 2017 to December 2020 were selected. According to the random number table, the patients were divided into conventional training group (16 males, 4 females, aged (45±10) years) and combined training group (13 males, 7 females, aged (39±8) years). Patients in conventional training group were given conventional rehabilitation therapy such as joint loosening, lower limb strength training, walking training, and pressure therapy, while patients in combined training group were given additional bicycle ergometer rehabilitation training on the basis of conventional rehabilitation. For patients in the 2 groups before and after a 2-month's treatment, the thickness of quadriceps was measured by ultrasonic diagnostic instrument, the muscle strength of quadriceps was measured by portable muscle strength tester, the walking ability was tested with a 6-min and a 10-meter walk tests, and the patients' satisfaction for treatment effects was assessed using the modified Likert scale. Data were statistically analyzed with independent or paired sample t test, Mann-Whitney U test, Wilcoxon signed rank test, or chi-square test. Results: After 2-month's treatment, the quadriceps thickness of patients in combined training group was (3.76±0.39) cm, which was significantly thicker than (3.45±0.35) cm in conventional training group (t=2.67, P<0.05); quadriceps thickness of patients in conventional training group and combined training group after 2-month's treatment was significantly thicker than that before treatment (with t values of 5.99 and 8.62, respectively, P<0.01). After 2-month's treatment, the quadriceps muscle strength of patients in combined training group was significantly greater than that in conventional training group (Z=2.69, P<0.01); quadriceps muscle strength of patients in conventional training group and combined training group after 2-month's treatment was significantly greater than that before treatment (with Z values of 3.92 and 3.92, respectively, P<0.01). After 2-month's treatment, the 6-min walking distance of patients in combined training group was (488±39) m, which was significantly longer than (429±25) m in conventional training group (t=5.66, P<0.01); the 6-min walking distance of patients after 2-month's treatment in conventional training group and combined training group was significantly longer than that before treatment (with t values of 13.16 and 17.92, respectively, P<0.01). After 2-month's treatment, the 10-meter walking time of patients in combined training group was significantly shorter than that in conventional training group (t=3.20, P<0.01); and the 10-meter walking time in conventional training group and combined training group was significantly shorter than that before treatment (with t values of 7.21 and 13.13, respectively, P<0.01). The patients' satisfaction score for treatment effects in combined training group was significantly higher than that in conventional training group (Z=3.14, P<0.01), and the patients' satisfaction scores for treatment effects in conventional training group and combined training group after 2-month's treatment were significantly greater than those before treatment (with Z values of 3.98 and 4.04, respectively, P<0.01). Conclusions: Bicycle ergometer rehabilitation training can be used to improve quadriceps thickness, muscle strength, and walking ability of patients with lower limb dysfunction caused by extensive burns. It can also improve the satisfaction of patients with the treatment outcome, and therefore is worthy of promotion.
Bicycling ; Burns/therapy* ; Female ; Humans ; Lower Extremity ; Male ; Prospective Studies ; Quadriceps Muscle ; Treatment Outcome ; Walking

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.