Objective To study the feasibility and indication of liver injury in children treated nonoperatively.Methods Ninteen(cases) with liver injury who underwent nonoperative management(NOM) were analyzed retrospectively.Patients with obvious trauma were reviewed.The main cause of trauma was due to traffic accident.Eleven cases(57.9%) had subcapsular hematoma and 8 cases(42.1%)had intrapararenchymatous hematoma.The treatment procedure included blood transfusion,hemostasis and monitoring the hemodynamic parameters.Results Seventeen cases(89.5%)were cured nonoperatively;2 cases underwent the operation later.Followed up for 10-24 months,patients were well recovered.Conclusions Most of cases with liver injury in children can be cured by NOM due to the physicalogical and anatomic features of children.During treatment,it is very important for the doctors to observe the vital signs closely,and(mana)-ge the combined injuries effectively and take regular imaging measurement.

Background:Clinical and epidemiological studies revealed that estrogen replacement therapy was associated with a significant reduction in risk of colorectal cancer in postmenopausal women.In our previous studies,estrogen increased the expression of mismatch repair (MMR)gene MLH1 in colonic cancer cells,and re-expression of MLH1 in MLH-deficient colonic cancer cells significantly increased the estrogen-induced apoptosis.Aims:To investigate the signaling pathway implicated in the MLH1-mediated apoptosis in colonic cancer cells induced by estrogen and the roles of p53 and its related genes in this apoptotic pathway.Methods:Plasmid containing wild type human MLH1 (hMLH1)full length cDNA was transfected into MLH1-deficient human colonic cancer cell line HCT116.By using HCT116 cells transfected with empty plasmid as controls,the apoptotic DNA ladder was determined by electrophoresis and the expressions of p53 and other apoptosis-related proteins were assessed by Western blotting under the condition with or without estrogen stimulation. Results:17β-estradiol (E2 )at the concentration of 10 -8 mol/L induced significant apoptosis in HCT116 cells transfected with hMLH1.In HCT116 cells transfected with hMLH1 and stimulated with E2 (group D),the protein expressions of caspase-3,caspase-9,p53,Bax and cytoplasmic cytochrome C increased significantly when compared with HCT116 cells stimulated with E2 only (group B);expressions of the abovementioned proteins were also higher in group D than in group C (transfected with hMLH1 only).Conclusions:MMR gene MLH1 is involved in estrogen-induced apoptosis of human colonic cancer cell line HCT116 by activating p53 signaling and mitochondrial apoptotic pathway.

Objective To observe a new phosphodiesterase-4 inhibitor Ro 20-1724 on ketamine anesthesia-induced learning and memory impairment and cAMP/PKA-CREB-BDNF signal pathway in immature rats.Methods Twenty-four 21 day-old SD rats were randomly divided into 4 groups (n=6 each):control group (group C) ;ketamine group (group K) ;ketamine+Ro 20-1724 group(group K+Ro) and ketamine+vehicle (0.1％ ethanol) group (group K+E).Ketamine 70 mg/kg was injected intraperitoneally(IP) once a day for 7 consecutive days in groups K,K+Ro,and K+E.Ro 20-1724 0.5 mg/kg and equal volume of vehicle were injected IP at 30 min after IP ketamine each time respectively.Morris water maze was used to assess learning and memory ability after 2 days normal feeding,the escape latency and frequency of passing the platform were recorded.The animals were killed after water maze test and the cAMP,PKA,p-CREB,and BDNF protein expression in hippocampus were detected.Results Repetitive ketamine anesthesia significantly prolonged the escape latency (P＜0.01),decreased the frequency of passing the platform(P＜0.01),and down-regulated the expression of cAMP,PKA,p-CREB,and BDNF protein ((280±31) pmol/mg vs (210± 19) mol/mg,P＜0.01 ; 1.32±0.11 vs 1.13±0.12,P＜0.01 ; 2.61 ±0.22 vs 2.03 ± ±0.19,P＜0.01 ; 1.51 ±0.14 vs 1.16±0.10,P＜0.05) ; Compared with group K,Ro 20-172,significantly attenuated the escape latency time(P＜0.05,P＜0.01)and increased the frequency of passing the platform(P＜0.01),and ameliorated the expression of cAMP,PKA,p-CREB,and BDNF protein ((210± 19) pmoL/mg vs (240± 27) pmol/mg,P ＜0.05;1.13±0.12 vs 1.28±0.12,P＜0.05;2.03±0.19 vs 2.32±0.21,2.32±0.21;1.16±0.10 vs 1.37±0.11,P＜0.01).There was no difference between group K+Ro and group C,and between group K+E and group K(P＞0.05).Conclusion ketamine anesthesia-induced learning and memory impairment can be improved by Ro 20-1724,and cAMP/PKA-CREB-BDNF signal pathway in hippocampus participated in the changes.

AIM: To evaluate the effects and safety of intravitreal injection of triamcinolone acetonide ( TA ) or conbercept combined with macular laser grid photocoagulation in the treatment of macular edema secondary to retinal vein occlusion( RVO) . ·METHODS: Fifty cases ( 50 eyes ) with macular edema secondary to retinal vein occlusion were selected and assigned to 2 groups: intravitreal injection of TA or conbercept, and laser photocoagulation after 7d. Best corrected visual acuity ( BCVA ) , fundus examination, optical coherence tomography ( OCT ) and intraocular pressure ( IOP ) were examined before intravitreous injection and 14d, 1 and 3mo after laser, fundus fluorescein angiography(FFA) were examined 3mo after treatment. The postoperative results at each time point were compared with preoperative values. · RESULTS: Two kinds of treatment compared with preoperative, the BCVA all increased in various degrees. At 14d after intravitreous injection, 1 and 3mo after laser, the ratio of vision improved in TA group was 76%, 80%, 68%, conbercept group was 88%, 92%, 88%, BCVA of two groups in each period all had varying degrees of increase than preoperative. The best BCVA acquired at 1mo after treatment. The macular thickness after treatment was significantly lower than preoperative in two groups. At preoperative, 14d, 1 and 3mo after treatment, the macular thickness in TA group was 557. 5 ± 150. 9,301. 7±120. 1, 262. 7 ± 131. 2, 338. 1 ± 146. 5μm; the macular thickness in conbercept group was 569. 4 ± 135. 9, 282. 3 ± 133. 5, 259. 5 ± 116. 4, 307. 8 ± 122. 6μm. The macular thickness of the two groups were significantly different between preoperative and postoperative. · CONCLUSION: The combination of intravitreous injection of TA or conbercept with macular laser grid photocoagulation can be an effective method in the treatment of macular edema secondary to RVO, conbercept treatment is more effective and security.

Objective To valuate the effect of Ro20-1724 on ketamine-induced apoptosis in hippocampal neurons of neonatal rats.Methods Hippocampal neurons from newborn Sprague-Dawley rats were obtained and cultured in vitro.The primary hippocampal neurons were randomly divided into 4 groups (n =24 each) using a random number table:control group (group C),ketamine group (group K),solvent control group (group E),and Ro20-1724 group (R group).The neurons were incubated for 72 h in the normal culture medium in group C.The neurons were incubated for 72 h in the culture medium containing ketamine 150 μmol/L in group K.In E and R groups,after the neurons were incubated for 30 min in the culture medium containing ketamine 150 μmol/L,the culture medium was then replaced,0.01％ ethanol (final concentration) and 1 × 10-3 μmol/L Ro20-1724 (final concentration) were added to the culture medium,respectively,and the neurons were then incubated for 72 h.After 72 h incubation,the cell viability was detected by MTT assay,the cell apoptosis was detected by flow cytometry,the expression of Bcl-2 mRNA and Bax mRNA was determined by RT-PCR,and synaptophysin Ⅰ expression was detected by Western blot.The apoptosis rate was calculated.Results Compared with group C,the survival rate was significantly decreased,the apoptosis rate was increased,the expression of Bcl-2 mRNA and synaptophysin Ⅰ was down-regnlated,and Bax mRNA expression was up-regulated in K and E groups (P ＜ 0.05 or 0.01).Compared with group K,the survival rate was significantly increased,the apoptosis rate was decreased,the expression of Bcl-2 mRNA and synaptophysin Ⅰ was up-regulated,and Bax mRNA expression was downregulated in R group (P ＜ 0.05 or 0.01).Conclusion Ro20-1724 can inhibit ketamine-induced apoptosis in hippocampal neurons of neonatal rats and correction of Bcl-2/Bax imbalance is involved in the mechanism.

Objective To observe the effect of Ro 20-1724 on social interaction ability of developing rats after repeated ketamine anesthesia.Methods 32 rats with 21 days old were randomly divided into four groups,control group (C group),ketamine group (K group),ketamine + Ro 20-1724 group (K + R group),ketamine + ethanol group (K + E group).Ethanol was used as a solvent of Ro 20-1724.Ketamine 70 mg· kg-1 was intraperitoneal injected,30 min later,to give or not give Ro 20-1724 0.5 mg · kg-1 or equivalent ethanol solvent for once each day for seven consecutive days.Then the rats were fed for three days.On the fourth day after the last administration,the social interaction ability were assessed in all rats.The expression of brain-derived neurotropic factor (BDNF) in hippocampal CA1 region was detected using conventional ELISA.Results Comparing with rats in C group,the time spent on the cage of lifeless body ((60 ± 29) min vs (109 ± 33) min,P ＜ 0.01),unfamiliar rats (103 ±35)min vs (151 ±42)min,P＜0.01;((123 ±34)min vs (184 ±46) min,P＜0.05) and familiar rats (89 ± 25) min vs (140 ± 38) min,P ＜ 0.01) in the social interaction test was significantly less in K group.The time spent significantly prolonged in group K + R,comparing with K group (lifeless body:(94 ± 34) min vs (60 ±29) min,P＜0.01) ;unfamiliar rat 1:(140 ±41) min vs (103 ±35)min,P＜0.05) ;unfamiliar rat 2:(171 ±45)min vs (123 ±34)min,P＜0.01) ; familiar rat:(133 ±35)min vs (89 ±25) min,P＜0.01).And there was no difference between K group and K + N group (P ＞ 0.05).The expression of BDNF in hippocampal CA1 region was significantly lower in K group,comparing with C group ((8.6 ± 2.7) ng/ml vs (11.8 ± 2.4) ng/ml,P ＜0.01) ; and there was a significant increase in K + R group,comparing with K group ((10.1 ± 3.6) ng/ml vs (8.6 ± 2.7) ng/ml,P ＜ 0.05).Conclusion Ro 20-1724 significant rescued social interaction impairment induced by ketamine anesthesia in developing rats.And BDNF in hippocampal CA1 region contribute to the reversal process.

Objective To investigate the effect of RO20-1724 on the cognitive function in immature rats after ketamine anesthesia.Methods Ninety-six SD rats of both sexes,aged 21 days,weighing 45-55 kg,were randomly divided into 8 groups ( n =12 each):control group (group C) ; ketamine group (group K) ; ketamine + normal saline group (group K + N) ; ketamine + anhydrous alcohol group (group K + A) ; ketamine + 4 different doses of RO20-1724 groups (group K + R1-4 ).The rats were anesthetized with intraperitoneal injection of kctamine 70 mg/kg in groups K,K+N,K+A and K+.R1-4.Normal saline 2 ml,anhydrous alcohol (in normal saline 2 ml),and RO20-1724 0.25,0.50,0.75 and 1.00 mg/kg (in anhydrous alcohol 8 μl and then in normal saline 2 ml) were injected intraperitoneally in groups K + N,K + A and K + R1-4 respectively 30 min later.Six rats from each group were randomly selected at 24 h after administration and Morris water maze was used to test the ability of learning and memory.Six rats from each group were sacrificed at 48 h after administration and hippocampus and cerebral cortex were removed for determination of the expression of CREB and phospho-CREB (p-CREB) by Western blot.Ressults Compared with group C,the escape latency was significantly prolonged at 2-4 days after administration,the number of animals' swimming across the platform decreased,and the expression of CREB and pCREB in hippocampus and cerebral cortex down-regulated in groups K,K+ N,K+ E,K+ R1 and K+ R2(P ＜0.05 ).Compared with group K,the escape latency was significantly shortened at 2-4 days after administration,the number of animals' swimming across the platform increased,and the expression of CREB and p-CREB in hippocampus and cerebral cortex up-regulated in groups K + R3 and K + R4 ( P ＜ 0.05).Compared with groups K + R1 and K + R2,the escape latency was significantly shortened at 2-4 days after administration,the number of animals' swimming across the platform increased,and the expression of CREB and p-CREB in hippocampus and cerebral cortex up-regulated in groups K+ R3 and K+ P4(P ＜ 0.05).There were no significant differences in the escape latency,the number of animals' swimming across the platform,and the expression of CREB and p-CREB in hippocampus and cerebral cortex between groups K + R1 and K + R2,and between groups K + R3 and K + R4 ( P ＞ 0.05 ).Conclusion RO20-1724 0.75-1.00 mg/kg can improve ketamine-induced cognitive dysfunction by up-regulating CREB and p-CREB expression in hippocampus and cerebral cortex in immature rats.

Objective To investigate the effects of RO20-1724 on repetitive ketamine administration-induced learning and memory impairment in immature rats.Methods Forty-eight 21-day-old SD rats of both sexes weighing 45-55 g were randomly divided into 4 groups (n =12 each):control group(group C); ketamine group (group K); ketamine + RO20-1724 group (group K+ R) and ketamine + vehicle (ethanol) group (group K+ A).Ketamine 70 mg/kg was injected intraperitoneally (IP) once a day for 7 consecutive days in groups K,K+ R and K+ A.RO20-1724 0.5 mg/kg and equal volume of ethanol were injected IP at 30 min after IP ketamine once a day for 7 consecutive day in groups K + R and K + A respectively.Morris water maze test was used to assess learning and memory ability.The escape latency and the number of times of passing the safe zone were recorded.The animals were killed after water maze test and their brains removed for microscopic examination of hippocampus and determination of p-CREB protein expression in hippocampus (by Western blot).Results Repetitive ketamine administration significantly prolonged the escape latency,decreased the number of times of passing the safe zone and down-regulated the expression of p-CREB protein in hippocampus on the 3rd and 4th day in group K as compared with group C.RO20-1724 significantly attenuated the above changes induced by repetitive ketamine administration in group K + R as compared with group K.Electron microscopic examination showed that RO20-1724 significantly ameliorated repetitive ketamine administration-induced hippocampal neuronal damage.Conclusion RO20-1724 can ameliorate cognitive dysfunction induced by repetitive ketamine administration.Up-regulation of cAMP /CREB signaling pathway is involved in the mechanism.

A solution with different Cu supply levels was cultured to investigate gama-aminobutyric acid (GABA) accumulation in Elsholtzia splendens, a native Chinese Cu-tolerant and accumulating plant species. Increasing Cu from 0.25 to 500 micromol/L significantly enhanced levels of GABA and histidine (His), but considerably decreased levels of aspartate (Asp) and glutamate (Glu) in the leaves. The leaf Asp level negatively correlated with leaf Cu level, while leaf GABA level positively correlated with leaf Cu level. The leaf Glu level negatively correlated with leaf GABA level in Elsholtzia splendens. The depletion of leaf Glu may be related to the enhanced synthesis of leaf GABA under Cu stress.
Copper ; toxicity ; Dose-Response Relationship, Drug ; Drug Tolerance ; physiology ; Gene Expression Regulation ; drug effects ; Lamiaceae ; drug effects ; metabolism ; Plant Leaves ; drug effects ; metabolism ; gamma-Aminobutyric Acid ; metabolism

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.