【Objective】 To investigate the expressions of NLRP1 and NLRP3 in the colon of ulcerative colitis (UC) patients and analyze the correlation of the expressions with severity of UC, endoscopic manifestations and related laboratory indicators. 【Methods】 We collected biopsical specimens obtained with colonoscopy in 46 patients with UC (22 mild cases and 24 moderate to severe cases) and 20 cases of normal control group. We used the disease activity index to evaluate the Mayo UC inflammatory activity and immunohistochemical method to detect the protein expression levels of intestinal mucosal NLRP1 and NLRP3 in the tissue. RT-PCR was used to detect the expressions of NLRP1 and NLRP3 mRNA in intestinal mucosal tissues. Meanwhile, the colonoscopy, serum uric acid, C-reactive protein, serum sedimentation rate, platelet count, low-density lipoprotein, and cholesterol of UC patients were also counted to further analyze the relationship between NLRP1 and NLRP3. 【Results】 The expressions of NLRP1 and NLRP3 protein and mRNA in colonic mucosal tissues of UC patients were significantly higher than those of normal controls (P<0.05). Compared with that in mild UC, the expression of NLRP1 in colonic mucosal tissues of moderate and severe UC patients was significantly increased (P<0.05). There was no significant difference in the expressions of NLRP1 and NLRP3 in colonic mucosal tissues of UC patients with different lesion ranges. NLRP1 expression was positively correlated with Mayo overall score, Mayo endoscopic score, erythrocyte sedimentation rate, and C-reactive protein (P<0.05), NLRP3 expression was positively correlated with C-reactive protein (P<0.05), but not correlated with Mayo overall score, Mayo endoscopic score, or erythrocyte sedimentation rate. NLRP1 expression was positively correlated with low-density lipoprotein and platelet (P<0.05), but not with uric acid or cholesterol. NLRP3 was positively correlated with low-density lipoprotein, uric acid and cholesterol (P<0.05), but not with platelet. 【Conclusion】 NLRP1 and NLRP3 may be involved in the pathogenesis of UC and related to disease activity. Therefore, they can be used as molecular targets for targeted therapy, and NLRP1 can be used as a predictor of mucosal healing.

Objective: To investigate the dosimetry differences of target and OARs of an integrated design of fields in IMRT and the mainstream IMRT technique for post-radical mastectomy. Methods: A total of 41 patients with post-radical mastectomy who received IMRT were eligible, the conventional fixing two-degrade collimator and the integrated IMRT fields were designed respectively. The dosimetry parameters of target and OARs, monitor units and delivery time of both plans were compared. Results: The dose distribution for targets and OARs of both plans met clinical requirements. The dosimetry parameters of target of both plans showed no statistically significant difference (P>0.05). Compared with the conventional technique, the integrated IMRT plans showed significant advantages, the ipsilateral lung V₅ decreased by 9.7%(t=2.407, P<0.05), V₁₀ 11.2%(t=2.160, P<0.05), V₂₀ 17.3%(t=2.465, P<0.05), V₃₀ 13.4%(t=2.119, P<0.05), D_mean 13.8%(t=2.258, P<0.05). And the heart V₃₀ decreased by 28.4%(t=2.589, P<0.05), D_mean 23.2%(t=2.409, P<0.05). The dosimetric differences of other OARS were not statistically significant(P>0.05). Conclusions The new method can effectively reduce exposed volume and exposed dose of ipsilateral lung and heart without affecting the target dose coverage. The method has universal applicability to patients with post-radical mastectomy who received IMRT, with important clinical significance.

The fatality rate of traumatic cardiac arrest (TCA) is extremely high, and it is very different from that of non-traumatic cardiac arrest (NTCA) in resuscitation strategy. Only when the standard resuscitation process is combined with rapid treatment of various reversible causes can the mortality rate of patients be decreased. In this paper, the key factors leading to TCA are reviewed, such as hypovolemic shock, asphyxia, tension pneumothorax, pericardial tamponade, crush syndrome, craniocerebral injury, cerebral hernia, and the control measures are elaborated respectively, so as to provide references for clinical treatment of patients with severe trauma, and reduce TCA incidence and mortality.

Adjuvants have been used as critical components of vaccine.They were used to stabilize the antigens and potentiate the immune responses.Dose sparing is also of interests in recent years to be applied in potential pandemic situations or to lower the costs of vaccines.With the emerging nanotechnology in many aspects including the use in biomedical applications,the application of nanomaterials as vaccine adjuvants also attracted a lot of attentions in recent years.With favorable biological properties,such as well-defined and well-formed nanoparticles,biocompatibility,biodegradability and ability to induce humoral immunity and cellular immunity simultaneously,calcium phosphate nanoparticles (CaP) have the potentials to be developed as an immune potentiator to be used as vaccine adjuvants.Here,we reviewed the basic properties of CaP and their applications as vaccine adjuvants with antigens of different modalities such as inactivated virus,protein and naked DNAs.The mechanism of the adjuvanting effects is briefly described.Further the development of CaP as vaccine adjuvants with some designed surface modification could lead to next generation vaccine adjuvants with improved immune potentiating properties and safety profiles.

Objective To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. Methods Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty?eight healthy male nude mice were randomly divided into 4 groups:the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E?cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E?cadherin mRNA were detected by real?time PCR. Results The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm3] and combination group [(507.74±77.50) mm3] were significantly lower than that of the control group (1355.33±189.04) mm3(P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level;0.54± 0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E?cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group ( 253. 78 ± 38. 87, 308. 94 ± 24. 67 vs. 213. 66 ± 30. 31 for protein expression level;2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both) . There was a significant negative correlation between ezrin protein and E?cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E?cadherin mRNA (r=-0.977, P<0.01). Conclusions Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non?small cell lung cancer xenografts and lymph node metastasis via down?regulated ezrin and upregulated E?cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.

Objective To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. Methods Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty?eight healthy male nude mice were randomly divided into 4 groups:the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E?cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E?cadherin mRNA were detected by real?time PCR. Results The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm3] and combination group [(507.74±77.50) mm3] were significantly lower than that of the control group (1355.33±189.04) mm3(P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level;0.54± 0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E?cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group ( 253. 78 ± 38. 87, 308. 94 ± 24. 67 vs. 213. 66 ± 30. 31 for protein expression level;2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both) . There was a significant negative correlation between ezrin protein and E?cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E?cadherin mRNA (r=-0.977, P<0.01). Conclusions Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non?small cell lung cancer xenografts and lymph node metastasis via down?regulated ezrin and upregulated E?cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.

Background:As the empirical studies on human body are restricted extremely,the establishment and selection of suitable animal models are important for researches on ulcerative colitis( UC ). Aims:To compare the symptoms and colonic pathology of rat models with experimental colitis induced by dextran sulfate sodium( DSS ) and trinitrobenzene sulfonic acid( TNBS),so as to provide a reference for selecting animal models in UC-related studies. Methods:Drinking 4% DSS freely for 7 days or intrarectal administration of single dose 100 mg/kg TNBS-50% ethanol were used to establish experimental colitis model in Sprague-Dawley rats. The disease activity index( DAI)was assessed dynamically during the course of experiment. The whole colon was removed in batches for measurements of colonic damage score and activity of myeloperoxidase(MPO)at different time points. Results:The DAI score reached the peak at the 7th day and the 2nd day in DSS group and TNBS group,respectively,and decreased gradually afterwards. Six and one deaths occurred during the experimental course in DSS and TNBS groups,respectively. In DSS group,the duration of inflammation was short,the colonic injury was moderate and recovered after drug withdrawal. At the 18th day,the colonic damage score and MPO activity was 0. 25 ± 0. 50 and(0. 80 ± 0. 33)U/g,respectively,and no significant differences were seen between DSS group and normal control group. In TNBS group,the duration of inflammation was longer and the colonic injury was more severe. At the 21st day,the colonic damage score and MPO activity was 3. 60 ± 0. 55 and( 1. 60 ± 0. 39 ) U/g, respectively,and chronic inflammation was observed histologically. Conclusions:Both DSS and TNBS can induce experimental colitis model in rats. The course of TNBS-induced colitis model presents a transformation of acute to chronic inflammation,and may be more suitable for treatment-related studies of UC.

OBJECTIVETo observe the effect of gut protease activity on visceral hypersensitivity in rats with acute restraint stress.

METHODSSprague-Dawley rats were given 30, 100 or 300 mg/kg camostat mesilate (CM), a protease inhibitor, or saline intragastrically 30 min before acute restraint stress induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk for 2 h. Visceral perception of the rats was quantified as the visceral motor response with an electromyography, and the rectal mucosa and feces protease activity and spinal c-fos expression were measured.

RESULTSCM dose-dependently reduced visceral sensitization elicited by rectal distension, but these doses did not completely inhibit stress-induced visceral sensitization. In normal rats, c-fos expression was found mainly in the superal spinal cord dorsal horn, and after the administration the CM, c-fos-positive cells decreased significantly in all dose groups (P<0.05). In 30 mg/kg CM group, fecal and rectal mucosal protease activity significantly decreased as compared with that in the stress group (P<0.05), and as CM dose increased to 100 and 300 mg/kg, the protease activity decreased even further (P<0.01).

CONCLUSIONThe gut protease is involved in acute stress-induced visceral hypersensitivity, and CM can lower the visceral sensitivity and spinal c-fos expression in rats.

Animals ; Gabexate ; analogs & derivatives ; pharmacology ; Protease Inhibitors ; pharmacology ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Sprague-Dawley ; Restraint, Physical ; Spinal Cord ; metabolism ; Stress, Physiological

OBJECTIVETo prepare the polyclonal antibody against methyl-accepting chemotaxis signal transduction protein (MCP) of Helicobacter hepaticus (H.hepaticus).

METHODSThe recombinant plasmid pET22b+/MCP was transformed into E.coli BL2l(DE3) to express the fusion protein His-rhMCP under the induction of IPTG. The fusion protein was purified and the antibody was obtained by immunizing rabbits. The titer of the polyclonal antibody was tested by indirect ELISA, and the specificity of the antibody was identified based on Western blotting using the prepared cell surface proteins (CSPs) of the bacteria.

RESULTSThe fusion protein was successfully expressed, and the titer of the antibody reached 1:32 000. Western blotting indicated that the antibody could specifically bind to CSPs and His-rhMCP.

CONCLUSIONThe antibody with a high titer and specificity was prepared to facilitate further study of the pathogenicity and epidemiology of H.hepaticus in human.

Animals ; Antibodies, Bacterial ; biosynthesis ; genetics ; Antibody Specificity ; Bacterial Proteins ; immunology ; Helicobacter hepaticus ; immunology ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Rabbits ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Signal Transduction

Objective To prepare the polyclonal antibody against methyl-accepting chemotaxis signal transduction protein (MCP) of Helicobacter hepaticus (H.hepaticus). Methods The recombinant plasmid pET22b+/MCP was transformed into E.coli BL2l(DE3) to express the fusion protein His-rhMCP under the induction of IPTG. The fusion protein was purified and the antibody was obtained by immunizing rabbits. The titer of the polyclonal antibody was tested by indirect ELISA, and the specificity of the antibody was identified based on Western blotting using the prepared cell surface proteins (CSPs) of the bacteria. Results The fusion protein was successfully expressed, and the titer of the antibody reached 1∶32 000. Western blotting indicated that the antibody could specifically bind to CSPs and His-rhMCP. Conclusion The antibody with a high titer and specificity was prepared to facilitate further study of the pathogenicity and epidemiology of H.hepaticus in human.