Objective To explore the influence of intraventricular injection of 5, 7-drhydroxytryptamine (5, 7-DHT)in 5-HT1A receptor sensitivity of medial prefrontal cortex pyramidal neurons in the rats,and to clarity the effect of 5-HT1A receptor on the eletronic response of pyramidal neurons.Methods 36 male SD rats were randomly divided into sham operation group (n=21)and 5,7-DHT lesion group (n=15).5,7-DHT was injected intraventricularly in the rats in 5,7-DHT lesion group,and the same dose saline was injected in the rats in sham operation group.The rats in two groups were intravenously injected with different doses(0.5-128.0μg·kg-1 )of 8-CH-DPAT.The firing rate of mPFC pyramidal neurons was recorded with extracellular electrophysioological examination.The rats in two groups were intravenously injected with WAY100635,the sensitivites of the rats to 8-OH-DPAT and WAY100635 in 5, 7-DHT lesion group were observed, and compared with sham operation group.Results The different doses (0.5-128.0μg·L-1 )of 8-OH-DDAT had an excitatory-inhibitory effect on the firing rate of mPFC pyamidal neurons in sham operation group;the neurons were excited when the doses of 8-OH-DPAT were 0.5-38.0μg·kg-1 ,and the firing rates were increased(P<0.05);the neurons were inhibited when the dose of 8-OH-DPAT was 128.0μg·kg-1 ,and the firing rate was decreased.The different doses(0.5-218.0μg·L-1 )of 8-OH-DPAT inhibited the elecctronic response of pyramidal neurons of the rats in 5,7-DHT lesion group in a dose-dependent manner (df=5,F=3.44,P=0.003),and the firing rates were reduced. WAY-100635 (50μg·kg-1 )reversed completely the inhibition of 8-OH-DPAT.Conclusion The sensitivity of 5-HT1A receptor of rat mPFC pyramidal neurons can be decreased by intraventricular injection of 5,7-DHT.

Drug-induced liver injury is commonly seen in ctinical practice and is usually caused by antipsychotic drags,antitubercnlar agents,paracetamol,and statins.Silybin,a substance with biological activity in silymarin extract,has antioxidant,anti-inflammatory,and anti-fibrosis effects.This article summarizes the research advances in silybin in the prevention and treatment of drug-induced liver injury.

ObjectiveTo investigate the protective effects of 5-hydroxy-1-methylhyantoin (HMH) on paraquat (PQ)-induced nephrotoxicity in rat and its possible mechanism.Methods Twenty-four male Sprague-Dawley (SD) rats were randomly divided into four groups: namely control, PQ, vitamin C and HMH groups, with 6 rats in each group. The rats in control group were given an injection of 2 mg/kg of normal saline intraperitoneally. The rats in PQ group were given an injection of 50 mg/kg of PQ intraperitoneally. The rats in vitamin C and HMH groups were given 1 mmol/kg of vitamin C or HMH through gastric tube right after PQ injection. The hydroxyl free radical scavenging ability of HMH and vitamin C was determined by Fenton method. Blood sample was collected after 24 hours of PQ treatment, then the animals were sacrificed and renal tissues were harvested. Blood urea nitrogen (BUN), serum creatinine (SCr), protein content of renal cortex, blood malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) activity were determined.Results Both vitamin C and HMH showed a very good ability to scavenge hydroxyl radicals, and the 50% inhibiting concentration (IC50) was both 4.02 mg/mL. Compared with control group, serum BUN, SCr and MDA in renal tissue were significantly increased in PQ group, and the protein, GSH contents and SOD activity were significantly decreased [BUN (mmol/L): 40.80±2.49 vs. 13.67±1.58, SCr (μmol/L): 163.46±8.67 vs. 51.80±4.37, MDA (nmol/g): 7.51±0.23 vs. 4.52±0.33, protein (μmol/L): 0.94±0.14 vs. 1.35±0.10, GSH (mg/g): 1.08±0.48 vs. 3.30±0.44, SOD (kU/L): 70.74±6.42 vs. 112.89±8.72, allP< 0.01]. Compared with PQ group, serum BUN and SCr and MDA in kidney tissue in vitamin C and HMH groups were significantly decreased, and GSH content and SOD activity in kidney tissue were significantly elevated [BUN (mmol/L):22.64±2.36, 18.71±5.23 vs. 40.80±2.49, SCr (μmol/L): 97.28±4.81, 89.20±6.72 vs. 163.46±8.67, MDA (nmol/g): 4.67±0.31, 4.21±0.42 vs. 7.51±0.23, GSH (mg/g): 1.78±0.10, 1.86±0.39 vs. 1.08±0.48, SOD (kU/L):98.69±5.43, 103.76±4.45 vs. 70.74±6.42, allP< 0.01]. Compared with vitamin C group, HMH could significantly reduce SCr contents (P< 0.05). There were no differences in reduction PQ-induced BUN, MDA content, and effect on GSH content and SOD activity between vitamin C group and HMH group (allP> 0.05).Conclusion HMH can protect the kidney against PQ-induced nephrotoxicity, and the mechanism of which maybe attributed to its anti-oxidation property and ability to scavenge hydroxyl radical.

Objective:To explore the early clinical features and the prognostic factors of children with septic shock in PICU.Methods:A retrospective analysis was conducted at PICU of the Children′s Hospital, Capital Institute of Pediatrics from January 2016 to November 2018, totally 56 children diagnosed as septic shock were enrolled in the study.According to the prognosis of 28 days, the patients were divided into death group and survival group; according to the lowest pediatric critical score (PCIS) within 24 hours after admission to PICU, the children were divided into non-critical group (>80 points), critical group (70-80 points) and extremely critical group (<70 points). The clinical characteristics of early stage in each group were analyzed and compared.Results:Of the 56 children with septic shock, 32 were males and 24 were females, and the mean age was 12.0(1.0, 180.0) months.The overall mortality rate was 37.5%(21/56). The mortality of non-critical group, critical group and extremely critical group were 12.5%(2/16), 16.7%(1/6) and 52.9%(18/34), respectively.There were no statistically significant differences between survival group and death group in gender and age, PICU stay time, heart rate, mean arterial pressure at 1 hour and 24 hours, ventilator using and the duration of mechanical ventilation(all P>0.05). The vasoactive-inotropic score(VIS) at 6 hours and 24 hours of death group were significantly higher than those in survival group[19.0(5.0-29.5) vs.5.0(0.0-10.0), 22.5(3.5-43.8) vs.5.3(0.0-13.5)]. The scores of PCIS in death group were less than that in survival group(57.3±10.7 vs.72.8±12.0)( t=4.85, P<0.001). The lactate level in survival group before resuscitation was statistically lower than that in death group[1.8(1.3-2.8) mmol/L vs.4.5(2.4-8.4)mmol/L]( Z<-3.70, P<0.05). At 1 hour, 6 hours and 24 hours after treatment, fluid resuscitation volume in death group were markedly higher than that in survival group[1 hour: (41.8±5.8)ml/kg vs.(38.5±5.3)ml/kg, t=-2.22, P<0.05; 6 hours: (69.5±4.4)ml/kg vs.(59.9±3.5)ml/kg, t=-8.96, P<0.05; 24 hours: (122.3±19.6)ml/kg vs.(111.7±16.2)ml/kg, t=-2.20, P<0.05]. Multiple sample comparisons found significant differences between the non-critical group[(60.0±3.5) ml/kg] and the extremely critical group[(65.3±6.0) ml/kg, P<0.05], and pairwise comparison of fliud intake within 1 h and 24 h showed no statistically differences( P>0.05). In the univariate analysis, variables significantly associated with death in septic shock were lactic acid before resuscitation and the 24 h lactate clearance rate, VIS 6 h, VIS 24 h, procalcitonin, ejection fraction, PCIS, 6 h-fluid resuscitation volume and multiple organ dysfunction (MODS). The Logistic regression showed that 6 h-fluid resuscitation volume, PCIS, lactic acid and MODS were independent risk factors.ROC curve analysis showed the AUCs of 6 h-fluid resuscitation volume, PCIS, early lactic acid and MODS for predicting death of septic shock children were 0.947, 0.835, 0.797 and 0.761, respectively. Conclusion:The mortality of septic shock is high, and decreased PCIS, elected serum lactic acid level and early fluid resuscitation, and MODS are risk factors associated with the death of septic shock.

Objective To improve the understanding of primary pulmonary artery sarcoma(PAS)and its early diagnosis and treatment.Methods The clinical data of 3 PAS patients in Beijing Anzhen Hospital and related literature,the clinical features,diagnosis and therapy of the disease were retrospectively studied.Results Pulmonary artery sarcoma had similar clinical presentations to pulmonary thromboembolism(PTE).Although CT pulmonary angiography and Color Doppler echocardiography etc were helpful to the diagnosis of the entity,the confirmed diagnosis needed the operation.The surgery was main therapy for the disease.Conclusion Pulmonary artery sarcoma is easily misdiagnosed as PTE.The clinicians should pay more attention to the disease so as to early diagnose and treat it.

Objective: To explore the clinical and echocardiography characteristics between noncompaction of ventricular myocardium (NVM) and dilated cardiomyopathy (DCM) combining hypertrabeculation in order to distinguish NVM from DCM.
Methods: Our research included 2 groups of patients: NVM group,n=31 and DCM combining hypertrabeculation group, n=50. The basic information as gender, age, family history, symptoms, ECG, plasma levels of BNP and echocardiography were recorded and examined in all patients; the size of cardiac chambers, myocardium, endocardium and hemodynamics were particularly focused. The trabeculation was analyzed by 17 segments method.
Results:①Compared with NVM group, the patients in DCM combining hypertrabeculation group had the worse cardiac classiifcation, higher plasma levels of BNP (P<0.05) and more obvious cardiac dilatation.②The patients in NVM group had the most trabeculation segments (9.82 ± 2.02) and the apical (17th segment) was involved, patients had the higher ratio of noncompacton/compaction (NC/C) as (2.84 ± 0.61), there were (4.12 ± 2.68) segments with NC/C > 2.③The patients in DCM combining hypertrabeculation group had the less trabeculation segments (5.56 ± 1.56) and the apical was seldom involved, patients had the lower ration of NC/C as (1.91± 0.42), there was at most 1 segment with NC/C > 2. All P<0.05.
Conclusion: Echocardiography is a simple, practical and noninvasive method to distinguish NVM from DCM. NVM could be diagnosed by obvious left ventricular apex involvement with NC/C >2 in at least 2 segments of free ventricular walls.

OBJECTIVETo explore the effect of Modified Hangqi Chifeng Decoction (MHCD) on levels of collagen type IV (Col IV), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) in extracellular matrix (ECM) of glomerular mesangial cells (GMCs) in LPS induced mice.

METHODSNormal serum and telmisartan, high, medium, low dose MHCD containing serums were prepared by using serum pharmacology method. GMCs were cultured in vitro. The proliferation of mesangial cells were induced using LPS as stimulating factor. GMCs were divided into six groups, i.e., the normal group, the model group, the telmisartan group, high, medium and low dose MHCD groups. Col IV content in the supernatant of mesangial cells was detected using ELISA. Protein expressions of MMP-2 and TIMP-2 were detected using Western blot.

RESULTSCompared with the normal group, Col IV content obviously increased in the model group after 72-h LPS stimulation; protein expressions of MMP-2 and TIMP-2 were obviously up-regulated, and MMP-2/TIMP-2 ratio was down-regulated in the model group (P < 0.01). Compared with the model group, Col IV content obviously decreased in high and medium dose MHCD groups and the telmisartan group (P < 0.01); protein expressions of MMP-2 were obviously down-regulated in medium and low dose MHCD groups (P < 0.01, P < 0.05); the protein expression of TIMP-2 was obviously down-regulated in high, medium, low dose MHCD groups and the telmisartan group (P < 0.01). The pro- tein expression of TIMP-2 was obviously lower in the high dose MHCD group than in the low dose MHCD group (P < 0.01). MMP-2/TIMP-2 ratio was obviously up-regulated in the telmisartan group, high and medium dose MHCD groups (P < 0.01).

CONCLUSIONMHCD could regulate disordered MMP-2/TIMP-2 ratio in LPS induced ECM, inhibit excessive production of Col IV in ECM, promote the degradation of ECM, reduce the accumulation of ECM, thereby, delaying the process of glomerular sclerosis.

Animals ; Cells, Cultured ; Collagen Type IV ; metabolism ; Extracellular Matrix ; metabolism ; Kidney Glomerulus ; cytology ; Matrix Metalloproteinase 2 ; metabolism ; Mesangial Cells ; drug effects ; Mice ; RNA, Messenger ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism

OBJECTIVE To explore the therapeutic effect of basic fibroblast growth factor (bFGF) coacervates on diabetic peripheral neuropathy (DPN) in diabetic rats.METHODS Poly (ethylene argininylaspartate diglyceride) (PEAD), heparin and bFGF were dissolved in saline at the mass ratio of 50:10:1 to obtain bFGF coacervates. The loading efficiency of bFGF in the coacervates was analyzed by Western blotting. The release profile of bFGF from the coacevates was detected by ELISA. Male SD rats were ip injected with streptozotocin 65 mg · kg- 1 to establish a diabetic model,and DPN occurred 8 weeks later. The DPN rats were randomly divided into free-coacervate group, bFGF group and bFGFcoacervate group. For bFGF group, bFGF 200 μg·kg-1 was im injected once daily for 3 d. In bFGF-coacervate group, bFGF coacervate solution (244 μL) equal to bFGF 200 μg · k - 1, was im given only once. DPN rats in free- coacervate group were im given the same volume of vehicle(PEAD + heparin) only once. Ten normal age peer rats were taken as normal control group.Footprint analysis was conducted each week to evaluate motor function. On the 30th day after treatment,the rats were sacrificed, and sciatic nerves of both sides were harvested for pathological observation through HE staining. Apoptosis in nerve tissue was detected by DAPI staining, and Ki67 and proliferating cell nuclear antigen (PCNA) protein levels were detected by Western blotting. RESULTS Western blotting and ELISA analysis indicated that bFGF-coacervates were well prepared at a mass ratio of 50:10:1,and controlled bFGF release for at least 35 d. The result of rat behavior evaluation and pathological index test indicated that, compared with normal control group, the sciatic function index (SFI) in free-coacervate group decreased significantly(P<0.01), the internal nerve fibers were accompanied by irregularity and serious demyelination, and there was a large number of apoptotic nuclei and low expressions of Ki67 and PCNA proteins (P<0.01).After injection with bFGF or bFGF-coacervates, the SFI increased progressively (P<0.05, P<0.01), and the proportion of fibers with myelin abnormalities and apoptotic cells was significantly reversed. Moreover, the levels of Ki67 and PCNA was evidently enhanced on the 30th day post- operation (P<0.05, P<0.01). Compared with bFGF group, the results of those detection indicators in bFGF-coacervate group were better (P<0.05, P<0.01). CONCLUSION PEAD and heparin complex can load bFGF with high efficiency, and control its release in a steady manner. For DPN rats,treatment with bFGF-coacervates is more effective than bFGF alone.

Objective To observe the influence on the sensitivity of pancreatic cancer cell line BxPC-3 to gemcitabine of silencing PAUF gene.Methods BxPC-3 cells,which overexpress PAUF,was stably transfected with PAUF-shCtrl and PAUF-shRNA to establish BxPC-3_shCtrl and BxPC-3_shPAUF cells as control and experiment group.Then the mRNA and protein expression level of PAUF in these two cell lines were detected by RT-PCR and western blot,respectively.The growth inhibition rates of these two cell lines treated with different concentrations of gemcitabine (0,3.1,6.25,12.5,25,50,100,200 nmol/L) were detected by MTT.Apoptosis rates in the cells treated with different concentrations of gemcitabine (0,75,100 nmol/L) were then observed by flow cytometry.Results The relative PAUF mRNA expression level in BxPC-3_shCtrl and BxPC-3 cells were 1.00 ± 0.06 and 0.83 ± 0.07,which were significantly high er than that in BxPC-3_shPAUF cells (0.25 ± 0.02;both P ＜ 0.05).The relative PAUF protein expression level in BxPC-3_shCtrl and BxPC-3 cells were 0.89 ± 0.07 and 0.95 ± 0.04,which were significantly high er than that in BxPC-3_shPAUF cells (0.31 ± 0.03;both P ＜ 0.05).The IC50 value of gemcitabine to BxPC-3_shCtrl cell was (22.88 ± 2.43) nmol/L,which was significantly higher than that of BxPC-3_shPAUF cells [(1.06 ± 0.02) nmol/L;P ＜ 0.05];apoptosis rate of BxPC-3_shPAUF cells treated by gemcitabine increased faster than that of BxPC-3_shCtrl cells.Conclusion PAUF silencing could greatly enhance the sensitivity of BxPC-3 cells to gemcitabine.