Tumor cells can metabolize glucose through glycolysis to intermediates for biomacromolecule synthesis by inhibiting the activity of the pyruvate dehydrogenase complex (PDC) in mitochondria. In this process, pyruvate dehydrogenase kinases (PDKs) play a key role. The inhibition of the activity of PDKs can effectively block this metabolic pathway, activate mitochondrial oxidative metabolism, and induce tumor cell apoptosis. PDK inhibitors have become a research hotspot in medicinal chemistry, and novel structures targeting classical binding sites have been synthesized. In this paper, recent research progress on PDK inhibitors is reviewed to provide information on these latest entities and to explore their clinical applicability.

CRISPR/Cas9 gene-editing system has been broadly used in various fields of bioscience and medicine in recent years. The system can be guided by RNA to specific DNA site thus achieving targeted gene editing.Off-target effect and editing efficiency remain to be two crucial challeges to the system. Currently, a number of researches have been focused on the optimization of the system by reducing off-target effects and increasing editing efficiency, which may enhance its safety and expand its application.

Objective To explore the therapeutic effects of statin in patients with chronic obstructive pulmonary disease (COPD) in stable period. Methods 83 patients with COPD in stable period were recruited and randomly divided into two groups, treatment group (n = 41) and control group (n = 42).The control group received conventional routine therapy, and treatment group was given rosuvastatin calcium 20 mg once per day on the basis of routine treatment. The levels of sera C-reactive protein (CRP), pulmonary function (FEV1、FEVl%pred), and COPD assessment test (CAT) were observed at the time points of 0 week and 12th week, 24th week and 48th week were compared between two groups. Results At 12th week after the treatment, sera CRP levels, FEV1, FEV1%pred and CAT scores in either control group or treatment group showed some extent of improvements as compared to those at the time point of 0 week, and there was statistical difference of sera CRP levels and CAT scores between two groups (P < 0.05). There was no statistical difference of FEV1, FEV1%pred between two groups (P > 0.05) .24th week and 48th week after the treatment; sera CRP levels, FEV, FEV1%pred and CAT scores in two groups all significantly improved and were statistical different between two groups (P < 0.05). Conclusion Statin can alleviate inflammatory reaction, improve pulmonary function and life quality of patients with COPD.

Objective　To compare the effects of mild hypothe rmic cardiopulmonary bypass (CPB) and moderate hypothermic cardiopulmonary bypas s in pediatric cardiac surgery. Methods　A total of 118 cas es of less than 3 years of age that had undergone open heart surgery were review ed, in which 46 patients received moderate hypothermic CPB(group 1) and 72 patie nts received mild hypothermic CPB(group 2). The CPB duration, incidence of low c ardiac output and postoperative concentration of CK-MK, etc, were compared with each other betwee n the two groups. Results　Duration of bypass and postoperative mechanical respiratory assistance of group 2 was shorter than that of group 1 ( P<0.05). Transfusion requirements, incidence of low cardiac output syndrome, concentration of CK-ME and percentage of metabolic acidosis were lower in grou p 2 than in group 1 (P<0.05), while the index of oxygenation was higher in g roup 2(P<0.05). Conclusion　The mild hypothermic CPB is saf er and more effective and therefore is superior to moderate hypothermic CPB in p ediatric cardiac surgery.

Objective To investigate the early clinical effects of percutaneous kyphoplasty in the treatment of age-related osteo-porotic vertebral compression fractures .Methods Retrospected 54 cases with osteoporotic verebral compression fractures were treated with PKP ,summarized early clinical effects and complications .analysis of preoperative and postoperative wound vertebral height average recovery rate ,Cobb Angle ,VAS scores and ADL scores .Results Operations in all the 54 cases were completed smoothly ,47 cases for 6 to 24 months follow-up(mean 13 .5 months) .postoperative pain in 31patients obtained remission immedi-ately ,1 week after operation ,12 cases with lower back pain and need the non-steroidal anti-inflammatory medications ,the symptoms remissed significantly or disappeared after 8 weeks postoperatively .At the last follow-up ,4 patients still had low back pain and need oral analgesics .Preoperative and postoperative wound vertebral height average recovery rate ,Cobb Angle ,VAS scores and ADL scores was statistically significant .Conclusion PKP is a minimally invasive ,effective and safe procedure that provides pain relief and stabilization of spinal stability and activities under the bed early ,and improves quality of life at the same time .Grasping the indi-cations Strictly and holding the surgical skills can be obtained clinical results efficiently and safely .

[ ABSTRACT] AIM:To investigate the role of canonical transient receptor potential channel 1 ( TRPC1 ) in the epithelial-mesenchymal transition ( EMT) of human bronchial epithelial ( HBE) cells induced by transforming growth fac-tor-β1 (TGF-β1).METHODS:EMT of 16HBE cells induced by TGF-β1 were identified by microscopy, immunofluores-cence and Western blotting.Immunofluorescence, real-time PCR and Western blotting were applied to detect the mRNA and the protein expression of TRPC1 in the 16HBE cells.The influence of SKF96365 (a TRPC1 blocker) and siRNA-me-diated silencing of TRPC1 on the EMT of the 16HBE cells were detected by microscopy and Western blotting.RESULTS:Treatment with TGF-β1 induced significant morphological changes of the 16HBE cells.Exposure to TGF-β1 decreased the expression of E-cadherin protein (P<0.01) and increased the expression of α-SMA protein (P<0.05) in the 16HBE cells.Immunofluorescence observation indicated that TRPC1 expression in the 16HBE cells was positive.The expression of TRPC1 at mRNA and protein levels was significantly increased in the 16HBE cells after stimulation with TGF-β1 ( P<0.05).The morphological changes of the 16HBE cells induced by TGF-β1 were inhibited by SKF96365 and TRPC1 silen-cing compared with TGF-β1 group.The protein expression of E-cadherin andα-SMA induced by TGF-β1 were inhibited by SKF96365 and TRPC1 silencing compared with TGF-β1 group (P<0.05).CONCLUSION:TGF-β1 induces EMT with the mechanism of up-regulating TRPC1 in human bronchial epithelial cells.

Objective To investigate the clinical value of double contrast-enhanced ultrasonography (DCUS) in the macroscopic classification of rectal carcinoma. Methods Seventy-one patients with rectal carcinoma were examined by ultrasound after intrarectal infusion and intravenous bolus injection of SonoVue preoperatively. And three types were divided according to the shape of the tumor:protruding type, ulcerative type and invasive type. After surgery, DCUS and perfusion contrast-enhanced ultrasonography (PCUS) were compared with final pathologic results respectively, and the relationship between general tumor type and TN staging were analyzed.Results The accuracy of DCUS [88.7%(63/71) ] in macroscopic classification of rectal carcinoma was significantly higher than that of PCUS [73.2%(52/71) ](χ2=5.534,P<0.05). For the invasion depth into the intestinal wall, the protruding type was mainly in T1, T2 and T3 stages while ulcerative and invasive type in T2, T3 and T4 stages (χ2=12.322, P<0.05 ). For the stage of lymph node, the protruding type was mainly in N0 and N1 while ulcerative and invasive type in N1 and N2(χ2=6.733,P < 0.05 ). Conclusions DCUS, with its high accuracy, is a new valuable method for macroscopic classification of rectal carcinoma.In the aspect of intestinal wall invasion and the lymph node, protruding type is less severe than ulcerative type and invasive type.

Objective: To investigate the mechanisms of electroacupuncture (EA) at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) in intervening diabetic gastroparesis (DGP) based on calcium-activated chloride channel. Methods: Forty Sprague-Dawley rats were randomly divided into four groups, including a normal control group (group A), a model group (group B), an EA group (group C) and a metoclopramide group (group D), with 10 rats in each group. A single intraperitoneal injection of 2％ streptozotocin (STZ) combined with 8-week high-glucose high-fat diet was used to establish a DGP rat model. After intervention, gastrointestinal propulsive rate was observed; the expression level of transmembrane protein 16A (TMEM16A) was examined by immunohistochemistry; the Ca2+ concentration in interstitial cells of Cajal (ICCs) was detected by immunofluorescence; and whole-cell patch-clamp technique was applied to detect the current intensity of calcium-activated chloride channel (ICaCC) in ICCs in gastric antrum. Results: After modeling, the blood glucose levels in group B, group C and group D were significantly increased compared with group A (all P<0.01); after intervention, compared with group B, the blood glucose levels in group C and group D were significantly decreased (P<0.05, P<0.01); the intra-group comparison of blood glucose level between after modeling and after intervention found significant difference only in group C (P<0.01). The gastrointestinal propulsive rates in group B, group C and group D were significantly different from that in group A (P<0.01 or P<0.05); the gastrointestinal propulsive rates were markedly higher in group C and group D than in group B (P<0.01, P<0.01). The expressions of TMEM16A in group B and group C were decreased compared with group A (P<0.01, P<0.05); the expressions of TMEM16A in group C and group D were increased compared with group B (P<0.01, P<0.05). The fluorescence intensity of Ca2+ was significantly lower in group B than in group A (P<0.01); the fluorescence intensity of Ca2+ was significantly higher in group C and group D than in group B (P<0.01, P<0.05). ICaCC in ICCs in group B was significantly decreased compared with group A; ICaCC in group C and group D were increased compared with group B. Conclusion: EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) can significantly improve gastrointestinal motility in DGP rats by up-regulating the ICaCC in ICCs.

OBJECTIVETo evaluate the effects of Icariin (ICA) on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro and in vivo.

METHODSAn enzymatic digestion block was used in vitro to culture hPDLSCs, which were separated and purified by limited dilution cloning. The hPDLSCs were identified using cell-surface markers and cocultured with 1 x 10(-7) mol.L-1 ICA solution. The proliferation ability of these cells was determined by thiazolyl blue tetrazolium bromide (MTT) assay. After staining with alkaline phosphatase (ALP), osteogenesis was detected by enzyme-linked immunosorbent assay. Osteoblast-related genes were analyzed by reverse transcription-polymerase chain reaction. Alizarin red staining was performed to measure the level of calcium deposition. The hPDLSCs were cocultured with 1 x 10(-7) mol.L-1 ICA and nano-hydroxyapatite scaffolds in vivo before transplantation into subcutaneous tissues of nude mice. Osteogenic abilities were histochemically analyzed after 30 days of induction.

RESULTSThe hPDLSCs were affected by 1 x 10(-7) mol.L-1 ICA, and MTT assay showed that the proliferation of the groups treated with ICA in vitro was better than that of the control groups on the second day. The ALP activity of the treated hPDLSCs was significantly enhanced after cell culture for 3, 5, and 7 days. The gene expression of osteoblastic markers was also significantly enhanced after 7 days. The deposition of mineralization after incubation with 1 x 10(-7) mol.L-1 ICA increased compared with the control after cell culture for 14, 21, and 28 days. Furthermore, the bone expression of the treatment groups in vivo was significantly enhanced compared with that of the control groups.

CONCLUSIONTreatment with 1 x 10(-7) mol.L-1 ICA can significantly promote proliferation and differentiation of hPDLSCs in vitro and in vivo. ICA can effectively function as a bioactive growth factor in periodontal tissue engineering to replace traditional growth factors.

Alkaline Phosphatase ; Animals ; Cell Culture Techniques ; Cell Differentiation ; Cell Proliferation ; Coculture Techniques ; Enzyme-Linked Immunosorbent Assay ; Flavonoids ; Humans ; Mice ; Mice, Nude ; Osteoblasts ; Osteogenesis ; Periodontal Ligament ; Stem Cells

Objective To discuss the efficiency of fibrin glue amikacin complex in controlling infection by observing the changes of leukocyte and neutrophilic granulocyte classifying counts after fibrin glue amikacin complex treated deep wound. Methods Clinical case-control study was used in the study. All patients were divided randomly into test group (100 patients) and control group (100 pa-tients), matched by wound location, wound size, time from injury to operation, combined injury and gen-eral antibiotics use to compare leukocyte and neutrophilic granulocyte classifying counts between both groups and observe possible toxic and side-effect in test group. Results Firstly, the test group and control group had the comparability in aspects of gender distribution, average age and injury mechanism (P >0.05). Secondly, there was statistical difference in classifying counts of leukocyte and neutrophilic granulocyte in the test group at different time points (P <0.05). The classifying counts of leukocyte and neutrophilic granalocyte peaked at 24 hours after operation, then decreased with treatment time and reached the lowest at 24 days after surgery or at day 1 before discharge. Thirdly, there existed statistical significance upon leukocyte counts in the test group and control group except for at day 1 after operation (P > 0.05), with lower counts in test group than control group. In aspect of neutrophil classifying counts, there was statistical significance (P < 0.05) at other time points in beth groups except for time points at days 1,2 and 12 (P >0.05). The test group had lower neutrophil classifying counts compared with con-trol group at different time points. Conclusion The fibrin glue amikacin complex has good clinical effort and high security, with no toxic or side effort in treatment of deep wound infection, and is worth clinical applicaiton.