Adult ; Humans ; Male ; Middle Aged ; Phosphines ; poisoning ; Young Adult

BACKGROUND:Gene therapy has become a new trend for disease therapy and brought promise for some refractory diseases. The key point is to choose the proper cell, gene and vector. OBJECTIVE:To investigate the effectiveness and feasibility of bone morphogenetic protein 2 (BMP2) gene transfected into endothelial progenitor cells (EPCs) from rat bone marrow for gene therapy. METHODS:The EPCs were isolated, cultured and identified from the bone marrow of Sprague-Dawley rats. Empty vector (LV-eGFP) or BMP2 gene (LV-eGFP-BMP2) was transferred into EPCs by the constructed lentiviral vector (LV). We examined the transfection efficiency by eGFP fluorescence, BMP2 secretion by ELISA, BMP2 expression by Western blot, and compared the capacities of migration, proliferation and anti-apoptosis after transfection in the three groups of normal EPCs, empty vector-EPCs, and BMP2-EPCs. RESULTS AND CONCLUSION:The transfection efficiency of lentiviral vector was 90%. BMP2 gene-transferred EPCs secreted and expressed more BMP2 proteins (P<0.01), and showed enhanced anti-apoptotic ability (P<0.05). The proliferation and migration capacity did not change obviously (P>0.05). After successful transfection with lentivirus-BMP2 gene, EPCs can secrete and express more BMP2 protein and show enhanced anti-apoptotic ability without obvious influence on the proliferation and migration capacity.

Objective To explore the clinical effectiveness of pressure-controlled ventilation-volume guar-anteed(PCV-VG)in obese patients with obstructive sleep apnea syndrome(OSAS)during uvulopalatopharyngo-plasty. Methods 40 obese patients(BMI≥30 kg/m2)with OSAS scheduled for uvulopalatopharyngoplasty under general anesthesia were randomly divided into two groups of volume-controlled ventilation(group V,n = 20)and pressure-controlled ventilation-volume guaranteed(group P,n=20). The heart rate(HR),mean arterial pressure (MAP),arterial partial pressure of oxygen(PaO2)and arterial partial pressure of carbondioxide(PaCO2)were recorded before induction of anesthesia without oxygen inhalation(T0),30 min(T1)and 1 h(T2)after tracheal intubation,and 30 min after extubation(T3). The peak airway pressure(Ppeak),airway resistance(Raw),thoracic compliance (CL),oxygenation index (OI) and respiratory index (RI) were also calculated at T1 and T2 under observation of recovery. Results There were no obvious differences between the two groups of patients before anesthesia and after recovery. Compared with the group V ,PaCO2 ,PPEAK ,Raw at T1 ,T2 and RI at T1 ~ T3 of the group P decreased(P<0.05),while CL at T1,T2 and PaO2,OI at T1~T3 increased(P<0.05). There were no sig-nificant differences in HR ,MAP at the above time points. Conclusions Compared with volume-controlled venti-lation,PCV-VG can effectively enhance thoracic compliance,lower inspiratory pressure and airway resistance ,and decrease intrapulmonary shunt ,which is conductive to improve arterial oxygenation and gas exchange in obese patients with OSAS.

Objective To investigate whether delayed treatment with exogenous kallikrein on neurogenesis after focal cortical infarction in stroke-prone renovascular hypertensive rats (RHRSP). Methods Seventy-two RHRSP were divided into 3 groups. Twenty-four rats were given human tissue kallikrein ( 1.6 × 10-2 PNAU/kg) and 24 rats were given vehicle through tail venous daily for 2 or 6 days consecutively starting at the 24th hour after distal middle cerebral artery occlusion (MCAO). 24 rats underwent sham-operation. Cell proliferation was examined by using 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg). Rats were respectively sacrificed 3, 7, 14 or 28 days after MCAO. Results Treatment with kallikrein significantly increased the number of BrdU+ cells in the ipsilateral subventricular zone (SVZ) (304.0±73. 9 vs 167.0±32.2 vs 56.0±12.2 at 7 d after operation, q =7.165, 12.916 and 5.751 respectively,all P<0.05) and in the peri-infarction region (490.0±82.0 vs 308.0±51.5 vs 49.0± 9.5 at 7 d after operation, q = 7.920, 19.184 and 11.264 respectively, all P < 0.01 ), and increased the number of BrdU+/DCX+ cells (225.0±13.6 vs 98.0±9.6 vs 23.0±5.6 at 7 d after operation, q = 30.731,48.735 and 18.004 respectively,all P < 0.01) in the ipsilateral SVZ compared with the vehicle group or the sham-operated group, which began on the 3 day, peaked in 7--14 days after MCAO, and then gradually decreased. Compared with the vehicle group, exogenous kallikrein markedly increased the number of BrdU+/NeuN+ cells (21.0±3.4 vs 13.0±2.6 at 14 d, P =0.001 ) in the peri-infarction region after MCAO. The kallikrein group showed a better functional improvement than the vehicle group after stroke ( all P < 0.05). Conclusion Our study suggests that administration of exogenous kallikrein at 24 h after cortical infarction enhances the SVZ neuroblasts proliferation, migration, and selective differentiation and improves functional recovery after stroke.

Objective To study the change and the significance of T-lymphocyte immune function in peripheral blood in population living in arsenic-contaminated area. Methods Fifty-three cases of patients with arsenism symptoms were selected into experimental group, inhabitants who had no chronic arsenism symptoms into control group in the endemic area of Shuocheng District, Shuozhou City, Shanxi Province in 2006. Vein blood samples were taken and analyzed with SAP assay to measure the percentage of CD3+ ,CD4+ and CD8+ T-cells. Results It was found that the percentage of CD3+, CD4+, and CD4+/CD8+ [(41.89 ± 11.58)%, (25.60 ± 9.05)% and 1.02 ± 0.41] in the experimental group was lower than that in the control group [(68.38 ± 7.23)%, (39.17± 4.28)% ,1.69 ± 0.56, t = 13.61,18.72,14.79, all P < 0.05], while there was no statistical differences of CD8+ [(25.30 ± 6.85)%] compared to the control group[(23.54 ± 8.35)%,t = 3.07,P > 0.05]. The gender-related effect of arsenic on CD4+ and CD8+ was found by multiple linear step regression analysis(t = - 3.05, - 4.30, all P < 0.05). In case group, there were no statistical differences in CD3+, CD4+, CD8+ and CD4+/CD8+[(40.65±10.06)%, (24.48 ± 6.29)%, (24.52 ± 8.16)%,0.98 ± 0.25] between males and females [(43.07±12.96)%, (26.77±3.12)%, (26.50 ±9.32)%, 1.07 ±0.41, t = - 0.76,3.05,0.30,2.10, all P > 0.05]. Conclusions The immune function of T-lymphocytes of patients with chronic arsenism has been suppressed. It is of active significance to detect T-lymphocyte subpopulation in peripheral vein in patients with chronic arsenism aiming at estimating the function of cell immune and providing early diagnosis index.

Objective To evaluate the effect of dexmedetomidine on hippocampal neuronal apoptosis in endotoxemic rats.Methods Twenty-four pathogen-free male Sprague-Dawley rats,aged 6 weeks,weighing 200-250 g,were randomly divided into 3 groups(n=8 each)using a random number table:control group (group C),endotoxemia group (group E),and dexmedetomidine group (group D).Dexmedetomidine 50 μg/kg was injected intraperitoneally,and lipopolysaccharide 5 mg/kg was injected via the caudal vein 30 min later in group D.Normal saline 2 ml was injected intraperitoneally,and lipopolysaccharide 5 mg/kg was injected via the caudal vein 30 min later in group E.Normal saline 2 ml was injected intraperitoneally,and normal saline 2 ml was injected via the caudal vein 30 min later in group C.At 12 h after the model was successfully established,Morris water maze test was used to assess the cognitive function.The escape latency,swimming distance and frequency of crossing the original platform were recorded,and the swimming speed was calculated.The rats were then sacrificed,and hippocampi were harvest for determination of neuronal apoptosis (by TUNEL) and expression of glucose-regulated protein 78 (GRP78),CAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 (by immunohistochemistry).The apoptosis index (AI) was calculated.Results There was no significant difference in the swimming speed between the 3 groups (P＞0.05).Compared with group C,the escape latency and swimming distance were significantly prolonged,the frequency of crossing the original platform was significantly decreased,and the AI was significantly increased,and the expression of GRP78,CHOP,and caspase-12 was significantly up-regulated in E and D groups (P＜0.05).Compared with group E,the escape latency and swimming distance were significantly shortened,the frequency of crossing the original platform was significantly increased,and the AI was significantly decreased,and the expression of GRP78,CHOP,and caspase-12 was significantly down-regulated in group D (P ＜ 0.05).Conclusion Dexmedetomidine reduces cognitive dysfunction probably through reducing hippocampal neuronal apoptosis mediated by endoplasmic reticulum stress in endotoxemic rats.

Objective To investigate the secondary degeneration of corticospinal tracts in cervical spinal cord following a recently cerebral infarct with diffusion tensor imaging(DTI) and its potential impact on neurological recovery.Methods Twenty-six patients with a focal cerebral infract underwent DTI at the first week, the fourth and twelfth week after stroke onset, respectively.The NIH Stroke Scale (NIHSS), the Fugl-Meyer motor scale (FM) and the barthel index (BI) were used to evaluate the neurological function before every DTI.Twenty-six gender and age match healthy volunteers underwent DTI three times at same time points.The DTI parameters of mean diffusivity (MD) and fractional anisotropy (FA value) were measured at the cervical spinal cord and initial lesion.Results Compared to the controls, the FA values of the contralateral side corticospinal tracts in the cervical spinal cord in patients significantly decreased at every observed time point (P<0.01).In patients group, the FA values of the contralateral side corticospinal tracts in the cervical spinal cord decreased progressively from 1~(st) week to 12~(th) week (P<0.01), but MD remained unchange.The absolute value of the percent reduction of FA value of the contralateral side corticospinal tracts in the cervical spinal cord in patients associated negatively with the absolute value of the percent change of NIHSS and FM (P<0.05), but not with the absolute value of the percent change of BI(P>0.05).Conclusions Conclusions: The secondary degeneration of the corticospinal tracts resulted from cerebral infarction may extend to the cervical spinal cord.Which may last at lest three months and thus hamper the process of neurological recovery.

Adolescent ; Apolipoproteins E ; blood ; Humans ; Hyperlipoproteinemias ; complications ; Hypolipidemic Agents ; therapeutic use ; Kidney Diseases ; blood ; drug therapy ; pathology ; Kidney Glomerulus ; blood supply ; pathology ; Male ; Thrombosis ; pathology

Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.