Hypoxia is an inherent feature of the majority of solid tumors,which can increase the resistance of tumor cells to radiotherapy and chemotherapy,promote tumor angiogenesis and lead to poor prognosis.Therefore,targeting the hypoxic tumor cells has become a spot in cancer therapy.Bioreduction drugs can be activated by a specific reduction to become cytotoxic metabolites,thus killing hypoxic tumor cells,while small molecular targeting inhibitors can selectively act on the key point of hypoxia pathway.They have paved a new way for hypoxia targeted therapy.

Animals ; Humans ; Signal Transduction ; Sphingomyelin Phosphodiesterase ; metabolism

Cardiomyopathy, Dilated ; genetics ; Humans ; NAV1.5 Voltage-Gated Sodium Channel ; Sodium Channels ; genetics

Helicobacter Infections ; complications ; Helicobacter pylori ; Hematologic Diseases ; complications ; Humans

Objective To measure the serum levels of endothelin-1 (ET-1) and transforming growth factor-β(TGF-β) in the newborns with respiratory distress and investigate its clinical significance. Methods Newborns with respiratory distress hospitalized into the Newborn Intensive Care Unit were included. The serum levels of ET-1 and TGF-β were all detected with ELISA in the first six hours,3,7,14 and 28 days after birth. Results The highest levels of ln ( 1 + ET-1 ) and ln ( 1 + TGF-β) were obtained from newborns with diagnosis as meconium aspiration syndrome ( 1.95 ± 1.02) ng/L and ( 1.51 ±0.99) ng/L,respectively) in the samples obtained in the first six hours after birth, and these were statistically different from those of the control group ( P ＜ 0. 05 ). Following were obtained for newborns with respiratory distress syndrome ( ( 1.52 ± 0.74 ) ng/L and ( 1.13 ± 0. 48 ) ng/L, t = 2.28,2. 13,respectively). After oxygen treatment, ET-1 levels obtained in the first six hours of life decreased gradually in the following days (P ＜0.05 ). Conclusions The measurements of ET-1 and TGF-β levels will help in differentiating diagnosis of the respiratory distress of newborns. The ET-1 levels will help to assess the therapy effectiveness and prognosis.

Owing to the positive interactions between different microorganisms, mixed fermentation has been found more and more effective in practice. Apparent progress has been made on the application and mechanism of mixed fermentation in past ten years, including: (1) degradation and utilization of cellulose, bagasse, cornstalk, etc; (2) degradation of environmental pollution, like Diazinon and PVA; (3) production of specifically metabolite; (4) optimized technics of mixed fermentation. The latest progress on the application, related mechanism, microorganisms, and conditions of mixed fermentation is reviewed in this article.

Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Musculoskeletal Manipulations ; methods ; Shoulder Dislocation ; diagnostic imaging ; therapy ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult

Objective　Recently,it was reported the analy sis of bone free radical by using electron spin resonance (ESR),so this article aimed to determine the changes of bone free radical in fluoresis rats.Methods　To analyze the free radical level of bone in fluoresis rats fed with different dose of calcium by ESR method.Results　The free radical of bone in the group of low ca lcium level and the group low calcium+fluorides was higher than that in the cont rol group (P<0.01),but that in normal animal feeds (calcium-rich)+fluoride group was lower than that in the control group.Conclusions　Low doses of fluoride did not resulted in the increase of free radical in calcium-rich condition at short time,but at low calcium condition,fluoride could increase the level of free radical,these suggested that simple overdose of fluoride did not change the level of free radical of bone.

Objective To investigate the effects of ulinastatin on autophagy and apoptosis of lung cells in rats with acute paraquat poisoning.Methods A total of 150 Wistar rats were randomly (random number) divided into three groups.The rats in control group had stomach lavaged once with 1 mL of normal saline followed by intraperitoneal injection of 1 mL normal saline twice a day.PQ poisoning model was produced by stomach lavaged once with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline once a day.In PQ + ulinastatin (PU) group,UTI in dose of 12 000 U/kg was intraperitoneally injected in rats twice a day.The lung tissue was obtained on the 7th day after modeling,and the histopathological changes were observed under microscope after hematoxylin and eosin (HE) staining.The positive expressions of autophagy-related LC3 protein LC3 and Bcl-2 pretein in lung tissue were observed after immunohistochemistry staining,and the levels of LC3、Bax 、Bcl-2 proteins were determined by Western blot.Results HE staining Results showed:it was observed from the PQ poisoning group that the abnormal cellular structure,enlargement in the pulmonary alveoli,leaking a lot of inflammatory cells,increased thickness of the alveoli wall and bleeding in the local area of lung tissue.Compared with the PQ poisoning group,the above changes in ulinastatin groups were relieved.Western blot Results showed:compared with the control group,the protein expressions of LC3-A/B were significantly increased in PQ poisoning group [LC3-A/B expression (A scale):0.22 ± 0.05 vs.0.14 ± 0.03,F =22.48,P ＜ 0.01].compared with PQ group,the expression of LC3 A/B obviously increased in the group of PU [LC3-A/B expression (A scale):0.36 ± 0.08 vs.0.22 ± 0.05,F =22.78,P ＜ 0.01].compared with Con group,the expression of Bcl-2/Bax obviously decreased in the group of PQ [Bcl-2/Bax expression (A scale),0.11 ±0.04 vs.0.83 ± 0.09,F =154.43,P ＜ 0.01].Compared with PQ poisoning group,the protein expressions of Bcl-2/Bax were obviously increased in PU groups [Bcl-2/Bax expression (A scale):(0.63 ± 018) vs.(0.11 ±0.04),F =154.43,P ＜0.01].Immunohistochemistry result:compared with Con group,the expression of LC3 and Bcl-2 obviously decreased in the group of PQ [LC3expression (A scale):(78.34±10.71) vs.(117.58±15.26),F=31.63,P＜0.01) (Bcl-2 expression (A scale):(62.54±9.74)vs.(130.52 ± 9.86,F =118.44,P ＜ 0.01).Compared with PQ poisoning group,the protein expressions of LC3 and Bcl-2 were obviously increased in PU groups [LC3expression (A scale):(162.58 ± 25.76) vs.(78.34 ± 10.71),F=31.63,P＜0.01]; [Bcl-2 expression (A scale):(145.56±10.26) vs.(62.54±9.74),F=118.44,P ＜ 0.01].Conclusions Theendoplasmic reticulum stress-autophagy is activated in the lung cells of rats with acute PQ poisoning.UTI can adjust endoplasmic reticul um stress,increased the expression of Bcl-2 and enhance the proportion of Bcl-2/Bax to protect the lungs of rats from acute PQ poisoning.

Objective To investigate the effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat (PQ) poisoning,and to explore its mechanism.Methods 200 Wistar rats were randomly divided into four groups by randomized arrangement table formed by computer,with 50 rats in each group.PQ poisoning model was reproduced by one time gastric lavage with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline (NS) once a day.The rats in control group were lavaged once with 1 mL of NS followed by intraperitoneal injection of 1 mL NS twice a day.The rats in Sal 0.5 and Sal 1.0 groups were intraperitoneal injected with 1 mL Salubrinal 0.5 mg/kg or 1.0 mg/kg on the 1st,3rd,and 5th day after PQ poisoning once a day.The lung tissue was harvested on the 7th day after poisoning,and the changes in histomorphology were observed using hematoxylin and eosin (HE) staining.The positive expression of autophagy-related protein LC3-Ⅱ in lung tissue was observed after immunohistochemistry staining,and LC3-Ⅱ and caspase-3 protein expressions were determined by Western Blot.Results HE staining results showed partial abnormal pulmonary structure in the PQ poisoning group:collapse of pulmonary alveoli,enlargement of the cavity,local infiltration of inflammatory cells,increasing thickness in the alveoli wall and obvious bleeding in the local lung tissue.Compared with the PQ poisoning group,the above changes in Sal 0.5 and Sal 1.0 groups were obviously relieved.It was shown by immunohistochemistry staining that compared with control group,the positive expression of LC3-Ⅱ was obviously decreased in the PQ poisoning group,Sal 0.5,and Sal 1.0 groups (A value:78.34 ± 10.71,76.52 ± 8.21,77.48 ± 9.11 vs.117.58 ± 15.26,all P＜0.05).There was no significant difference in positive expression of LC3-Ⅱ between each of the later three groups (all P＞0.05).Western Blot results showed:compared with the control group,the protein expressions of LC3-Ⅱ and caspase-3 were significantly increased in PQ poisoning group [LC3-Ⅱ (A value):0.22 ±0.05 vs.0.14 ±0.03,caspase-3 (A value):0.115 ± 0.013 vs.0.023 ± 0.006,both P＜0.05].Compared with PQ poisoning group,the protein expressions of LC3-Ⅱ and caspase-3 were obviously decreased in the Sal 0.5 and Sal 1.0 groups [LC3-Ⅱ (A value):0.19 ±0.05,0.18 ±0.04 vs.0.22 ±0.05; caspase-3 (A value):0.078 ±0.012,0.076 ±0.010 vs.0.115 ±0.013,all P＜0.05].Conclusions The endoplasmic reticulum stress-autophagy is activated in the pulmonary cell of acute PQ poisoning rats.Salubrinal can decrease the autophagy and apoptosis in the lung of rats with acute PQ poisoning,which play a role in the treatment.