Objective To investigate the therapeutic effect and mechanism of NLRP3 inflammasome inhibitor-dapansutrile(OLT1177)-against acute radiation lung injury.Methods Mice were divided into the control group,OLT1177 injection group,irradiation group,and irradiation+OLT1177 injection group.A single dose of 22 Gy whole-lung 60Co radiation was used to establish a model of acute radiation lung injury.After 6 h of radiation,OLT1177(100mg/kg,once daily)was administered intraperitoneally.After 14 consecutive days of administration,lung tissues were collected and weighed while the lung coefficient was calculated.Hematoxylin-eosin(HE)staining and F4/80 immuno-histochemical staining were used to observe the pathological changes and inflammatory cell infiltration in lung tissues.Real-time quantitative PCR(qPCR)was used to detect the transcription levels of NLRP3,IL-1β,and other mRNAs in lung tissues.Serum cytokines such as TNF-α and IL-6 were measured by cytometric bead array(CBA).The activation of Caspase-1 and IL-18 was detected by Western blotting.Results Radiation caused acute inflammation in the lung tissues of mice,manifested as edema in the lung tissues and destruction of the alveolar structure,increased macrophage infiltration,and elevated expressions of inflammatory genes NLRP3,IL-1β,TNF-α,and IL-6 in the lung tissues and higher serum levels of TNF-α,IL-6.Treatment with OLT1177 significantly improved the above symptoms induced by radiation.OLT1177 inhibited the activation of NLRP3 inflammasome downstream Caspase-1 and IL-18 induced by radiation.Conclusion OLT1177 can significantly alleviate acute radiation lung injury in mice,which may be due to its inhibition of NLRP3 inflammasome activation induced by radiation.

Objective To investigate the role and mechanism of suramin(Sur)in acetaminophen(APAP)-induced acute liver injury in mice.Methods 8-10 weeks old C57BL/6J mice were randomly divided into the APAP group and APAP+Sur group(20 mg/kg suramin was injected 1 h before).After 18 hrs of fasting,400 mg/kg APAP was injected intraperitoneally to establish a mouse model of acute liver failure and the survival rate was recorded.An acute liver injury model of mice was established via intraperitoneal injection of 300 mg/kg APAP(other conditions remained unchanged).A control group was also established,with liver tissues and serum collected at 0,2,and 12 hours post-APAP treatment.ELISA and CBA techniques were adopted to detect the release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum and the secretion of inflammatory factors.H&E staining and immunohistochemistry were used to detect liver tissue necrosis and inflammatory cell infiltration.DCFA-DH and ELISA techniques were used to detect the levels of reactive oxygen species(ROS),malondialdehyde(MDA)and glutathione(GSH)in liver tissues.Western blotting was employed to assess the activation of the JNK signaling pathway in liver tissues.Results Suramin treatment improved the survival rate of APAP-induced mice,reduced the release of transaminases and inflammatory factors in serum,and alleviated APAP-induced liver cell necrosis and inflammatory cell infiltration in the liver.Suramin treatment delayed APAP-induced GSH depletion in the liver,reduced MDA and ROS levels,and inhibited JNK pathway activation.Conclusion This study has confirmed the protective effect of suramin against acetaminophen-induced acute liver injury in mice.The mechanism is potentially related to oxidative stress and inflammation.

The pathological position of hypersecretion of airway mucus is in airway mucosa. Modern TCM theory believes that the airway mucosa belongs to the triple energizer membranous system of TCM, and the airway mucus is a part of TCM water-liquid system. Based on the TCM physiological characteristics of children, this article explored the pathogenesis of airway mucus hypersecretion in children, and believed that the airway mucus hypersecretion was the result of the disorder of water-liquid metabolism in TCM, which was closely related to the function of qi transformation of triple energizer membranous system. Failure of qi transformation in triple energizer is the core pathogenesis of hypersecretion of airway mucus in children. The deficiency of yang qi in children leads to the disorganization of vaporization in triple energizer, which leads to the insufficiency of movement and transformation function, the failure of water and qi in water, the stop of water and water accumulation, the abnormity of water and grain. The disorder of water-liquid metabolism leads to the occurrence of high airway mucus secretion in children.

Objective:To investigate the effect and underlying mechanism of BRCC3 knockout on acute GVHD(aGVHD) of mice.Methods:A total of 12 recipient C57BL/6J mice were divided into two groups, including 6 wild type(WT) and BRCC3 -/-(KO). The recipients were exposed to 4.5 Gy + 4.5 Gy 60Co γ-rays in total body irradiation (TBI) at 30 min intervals. At 6 h post-irradiation, 1×10 7bone marrow cells and 8×10 6 splenocytes from BALB/c mice were infused into C57BL/6J mouse via tail vein to develop aGVHD mouse model. BRCC3 was specifically knocked out in aGVHD mouse model. The organ damage was examined through histopathology. The levels of serum cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cytometric bead array (CBA), respectively. Spleen, liver and small intestine lymphocytes were isolated at 9 d post-transplantation, and the infiltration and activation of T cells in the target organs were assayed using flow cytometry. Results:The absence of BRCC3 in recipient mice significantly shortened survival ( P<0.05) with increased liver injury of aGVHD mice. In BRCC3 -/-recipient mice, the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly higher than those in the spleen( t=6.53, 5.52, P<0.05), and the proportions of CD8+ T cells and CD8+ CD25+ T cells were significantly increased in the liver ( t=3.74, 3.19, P<0.05). Similarly, the proportions of CD8+ T cells, CD8+ CD25+ T cells and CD8+ CD69+ T cells were significantly elevated in the small intestine ( t=3.52, 4.06, 3.29, P<0.05). Conclusions:BRCC3 deletion increased the proliferation and activation of donor CD8+ T cells and aggravated aGVHD, which might provide a new prevention and treatment target for aGVHD.

OBJECTIVE: To carry out G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA) for a fetus featuring multiple malformations. METHODS: The fetus was found to have increased nuchal thickness, generalized edema, asymmetric lower limbs, tetralogy of Fallot, nasal bone anomaly and cleft palate. Following amniocentesis, G-band karyotyping and CMA were carried out. RESULTS: The fetus had a karyotype of 47,XX,+i(12)(p10) [14]/46,XX[6]. CMA has identified a 33.9 Mb duplication at 12p13.33-p11.1, which was suggestive of tetrasomy 12p. CONCLUSION Combined chromosomal karyotyping and CMA can delineate the origin of abnormal chromosomal fragments during prenatal diagnosis. The fetus was diagnosed with Pallister-Killian syndrome.

Objective To determine the effect of ostecytic TGF-β/Smad4 signaling on osteoblastic and osteoclastic differentiation in bone marrow stromal cells (BMSCs).Methods Mice with osteocytic TGF-β/Smad4 conditional knock down (Smad4ot CKD) were generated as previously by crossing DMP1-8kb-Cre mice with Smad4lox(ex8)/lox(ex8) mice.The osteocytes were isolated from tibial and femoral diaphysis and co-cultured with wild-type BMSCs.ALP staining, Alizarin red staining and TRAP staining were performed to show osteoblastic and osteoclastic differentiation.Then, their marker genes were detected by qPCR and proteins measured by Western blot.ResultsThe expression of Runx2 and Osterix were reduced in smad4 CKDot co-cultured with BMSCs compared with controls(P<0.01).Similarly, the specific markers of osteoblastic differentiation were decreased (P<0.01).Additionally, the expression of RANKL was not significantly changed in with BMSCs.However, OPG was highly expressed incontrol group compared with smad4 CKD in co-cultured group (P<0.05).Thus, the radio of RANKL/OPG was significantly reduced (P<0.05).Furthermore, the expression of RANK was inhibited.Conclusions The terminally-differentiated osteocytes are the cells regulating bone metabolism, while down-regulation of osteocytic-TGF-β/Smad4 inhibits BMSC osteoblastic and osteoclastic differentiation.

Adipocytes ; cytology ; Humans ; Stem Cell Transplantation ; methods ; Stroke ; therapy

This study was aimed to establish a method for assay of 4-terpineol, α-terpineol, bornyl acetate and methyl-n-nonylketone in Houttuynia cordata with gas chromatography-mass spectrometry (GS/MS) for the first time in order to provide experimental evidences for its quality control. Undecylen was analyzed quantitatively. GC/MS method was used in the content determination of 4 kinds of components in Houttuynia cordata. GC conditions were that the temperature was firstly increased to 70oC for 5 min, and then 5oC·min-1 to 140oC for 5 min. Then, the temperature was increased by 10oC·min-1 to 250oC for 10 min. The temperature of the injection port was 230oC. The carrier gas was high purity helium. The flow rate was 1.0 mL·min-1. The split ratio was 10:1. The sample quantity was 1 μl. MS conditions were that the detector was MS, EI was 70ev, the temperature of four poles was 150oC, the temperature of ion source was 230oC. The results showed that there was good linearity of four components, which were 4-terpineol, α-terpineol, bornyl acetate and methyl-n-nonylketone obtained within the ranges of 6.492~129.84μg·min-1, 1.097~21.944 μg·min-1, 12.128~242.56 μg·min-1, and 84.76~169.52 μg·min-1, respectively. The average recoveries of the four components were 81.2%, 80.6%, 88.3%, and 84.6%, respectively. The RSDs were 1.5%, 2.3%, 1.1%, and 0.7%, respectively. It was concluded that the method was simple, sensitive, and easy to operate. The simultaneous measurement of multiple indexes on the component for quality evaluation of Houttuynia cordata can effectively reflect the quality of Houttuynia cordata. It can also be used in the quality assessment of fresh Houttuynia c ordate .

OBJECTIVETo investigate the clinical effects of wrist joint fixation in flexion-ulnar position for the treatment of Colles fracture.

METHODSFrom January 1998 to June 2008,120 patients with Colles fracture were treated with wrist joint fixation with plaster in flexion-ulnar position. There were 52 males and 68 females with an average age of 57.6 years (ranged, 22 to 90); 41 cases were left, 69 cases were right, and 10 cases were hibateral. All of them were fresh closed fractures. According to fracture displacement to typing, type I of 34 cases, type II of 36 cases, type III of 32 cases, type IV of 18 cases.

RESULTSWith dislocated (II-IV type) 86 patients were followed up for 10 months in average. 86 cases with displaced fragments achieved clinical bony union. According to standard of Dienst, 59 cases got excellent results, 12 good, 10 fair, and 5 poor.

CONCLUSIONThe wrist fixation with plaster in flexion-ulnar position in treating Colles fracture may maintain good fixation after reduction and obtain better functional recovery.

Adult ; Aged ; Aged, 80 and over ; Biomechanical Phenomena ; Casts, Surgical ; Colles' Fracture ; physiopathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Recovery of Function ; Wrist Joint ; surgery

Objective:To evaluate the clinical efficacy of maintenance chemotherapy for patients who had local advanced non-small cell lung cancer (NSCLC) and was responsive to primary radiotherapy and chemotherapy. Methods:One hundred and twenty patients with stage ⅢA or ⅢB NSCLC received 4 cycles of chemotherapy combined with radiotherapy. The 63 patients who achieved certain remission were randomly divided into maintenance chemotherapy group(n=33) and control group(n=30). The patients in maintenance chemotherapy group (treatment group) received vinorelbine (20 mg/m2, d 1 and d 8, per 28 d a cycle) and those in control group were not given maintenance chemotherapy. The clinical efficacy, survival rate and adverse reaction of the two groups were evaluated. Results:There are a longer median time to progression(TTP) in treatment group compared with control group (8.5 month vs 5.0 month, P<0.05). The 1-and 2-year survival rates were 66.7% and 36.4% in the treatment group and 60.7% and 32.1% in the control group, respectively. The difference between the survival rates of two groups was not significant (P>0.05). Conclusion:Maintenance vinorelbine-based chemotherapy prolonged the median time to progression but had no effect on survival time in patients with local advanced NSCLC who responded to induction chemotherapy.