Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.

To investigate the effect of mitochondrial division inhibitor 1(Mdivi-1)on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its mechanism,female 8-week-old C57BU6 mice were recruited and randomly divided into control group,IMQ model group,IMQ+Mdivi-1 experiment group.IMQ was used to induce the psoriasis-like skin inflammation model in mice.The mice in the experiment group were injected intraperitoneally(i.p.)with Mdivi-1,and the mice in the control group and model group were injected with the same volume of solvent.The mice were sacrificed on the 7th day for sampling.Psoriasis area and severity index(PASI)score was used to evaluate the severity of skin lesions in each group;the reactive oxygen species(R0S)content in skin tissue was detected by fluorescence staining of frozen section;HE staining was used to observe the histomorphologic change of skin lesions;immunohistochemical staining was used to detect the expression of dynamin-related protein 1(Drp1)in the skin of mice;Western blot was used to detect the protein levels of Drp1,NLRP3 and IL-1β in the skin tissues of mice in each group;and the expressions of IL-17A and IL-18 in mouse serum were detected by ELISA.Data showed that the model group had typical psoriatic lesions such as erythema,scale and thickening,and the Mdivi-1 group demonstrated obvious reduction of the lesions.The PASI score of the experiment group was significantly lower than that of the model group.HE staining indicated that the epidermal thickness of the back skin in the treatment group was significantly lower than that in the model group,and Munro microabscess was significantly reduced.R0S fluorescence staining indicated that ROS content in the experiment group was significantly lower than that in the model group;immunohistochemical results showed that the expression of Drp1 protein in the experiment group was significantly lower than that in the model group;Western blot results showed that the expression levels of Drp1,NLRP3 and IL-1 β in the experiment group were significantly lower than those in the model group;ELISA results indicated that the expressions of IL-17A and IL-18 in serum of mice in the experiment group were lower than those in the model group.Taken together,Mdivi-1 can reduce mitochondrial damage and ROS production by inhibiting the expression of Drp1,thereby reducing the production of NLRP3 inflammasome,down-regulating IL-1 β,IL-18 and IL-17A,and alleviating the IMQ-induced psoriasis-like skin inflammation in mice.

Objective To cxplore the variation of the range of motion (ROM) of operative level after different heights of artificial cervical disc replacement,and to provide guidance for clinical work in selecting appropriate height of artificial cervical disc prosthesis.Methods The preoperative cervical anteroposterior and lateral Ⅹ-rays of 9 fresh male cadaveric cervical spine specimens were obtained to measure the intervertebral height of C5-6,and 3 screened specimens with the height of about 5 mm were included in the experiment.The experiment was designed to test self-control,and other four groups of cervical specimens including intact group,appropriate height (5 mm) of C5.6 artificial cervical disc replacement group,1mm increased (6 mm) group and 2 mm increased (7 mm) group were made biomechanical test sequentially.The specimens were fixed to the cervical three-dimensional movement machine,with a 75 N follower load and pure moments of 2 Nm for flexion/extension 、left/right bending and left/right axial rotation,to measure the ROM of operative level under the condition of changes in 0.2 Nm/s.Results There were no significant differences in the ROM of flexion/extension,lateral bending and axial rotation between 5 mm group and intact group;the ROM of flexion/extension、lateral bending and axial rotation in 6 mm group increased compared with 5 mm group,but the difference was not statistically significant;the ROM of flexion/extension in 7 mm group was significantly less than that of intact,5mm and 6 mm group (9.5°± 1.0° vs 12.5°±0.9°、11.3°±0.8°、11.6°±0.9°),but significantly greater in axial rotation than 6 mm group (10.4°±1.4°vs 8.6°±0.3°),and there was no significant difference in lateral bending compared with other 3 groups.Conclusion 2 adjacent heights of cervical disc prostheses are implantedsuitably when testing the mold of disc prosthesis,the choice of cervical disc prosthesis with 1 mm increased can improve the ROM of operative level to some extent;while the height with 2 mm increased can lead to the ROM of flexion/extension at the operative level reduced,but the ROM of rotation shows an increasing trend.

Objective To evaluate the effects of modified early goal directed therapy (EGDT )on the prognosis of patients with septic shock .Methods Clinical data of 116 patients with septic shock admitted to ICU during January 2011 to March 2013 were retrospectively analyzed .Patients were divided into modified early goal‐directed therapy group (n=57) and traditional early goal‐di‐rected therapy group (n=59) according to different methods of treatment ,the patients′28‐day survival rates of these 2 groups were compared .Modified early goal‐directed therapy are divided into survival group (n=46) and non‐survival group (n=11) according to 28‐day prognosis .Acute physiology and chronic health evaluation Ⅱ (APACHEⅡ ) score ,sequential organ failure assessment (SOFA) ,multiple organ dysfunction syndrome (MODS) score and other relevant indicators of survival group and non‐survival group were compared .Results The 28‐day survival rate in modified early goal‐directed therapy group had increased approximately 18 .9% higher than that of the traditional early goal‐directed therapy group(P< 0 .05) .The APACH Ⅱ score ,SOFA score and MODS score in non‐survivors were significantly higher than those of survivors in modified EGDT group ,which were[(29 .36 ± 1 .57)d vs .(24 .30 ± 3 .27)d] ,[(13 .45 ± 0 .52)d vs .(12 .78 ± 1 .33)d] ,[(9 .00 ± 0 .00)d vs .(4 .04 ± 1 .94)d]separately .And vaso‐pressors time and mechanical ventilation time was significantly longer in non‐survivors than survivors(P<0 .05) .Conclusion Mod‐ified early goal directed therapy could improve 28‐day survival rate ,and it show s beneficial effects on outcome of critical patients w ith septic shock .

We investigated the effects and optimal treatment frequency of pulsed electromagnetic fields (PEMFs) on postmenopausal osteoporosis (PMO). A comparison was performed with the cyclical alendronate and a course of PEMFs in the treatment for postmenopausal osteoporosis on bone mineral density (BMD), pain intensity and balance function. There was no significant difference between the two groups on mean percentage changes from baseline of BMD within 24 weeks after random treatments (P > or = 0.05). However, at the ends of 48 weeks and 72 weeks, the BMD of the PEMFs group were significantly lower than that of the alendronate group (P < 0.05). No significant difference was detected between the two groups with regard to treatment effects on Visual Analogue Scale score, the Timed Up & Go Test and Berg Balance Scale score. Compared with cyclical alendronate, a course of PEMFs was as effective as alendronate in treating PMO for at least 24 weeks. So its optimal treatment frequency for PMO may be one course per six months.
Alendronate ; therapeutic use ; Bone Density ; Bone Density Conservation Agents ; therapeutic use ; Electromagnetic Fields ; Female ; Humans ; Magnetic Field Therapy ; Osteoporosis, Postmenopausal ; therapy

Objective To investigate the therapeutic effect of 4-1BB monoclonal antibodies (4-1BBmAb) and glucocorticosteroid and the affect of the expression of CD4+CD25+T lymphocytes on the mouse hepatitis induced by ConA.Methods Mouse model of hepatic injury was induced by the application of ConA and checked by hepatic function tests and hepatic pathology.Mter the animal models were constructed,the mice in the group of therapeutic alliance were treated with glucocorticosteroid and 4-1BBmAb.In contrast,mice in the control group were treated with 4-1BBmAb or glucocorticosteroid alone.The groups were then compared.After blood was collected respectively from the control group,the model group and the therapy group,flow cytometry was used to examine CD4+CD25+T lymphocytes.Chi-square test and t-test were used for statistical analysis.Results Compared with the control group,the conditions of the mice were improved after being disposed with 4-1BBmAb.The conditions became even better when 4-1BBmAb were used combined with glucocorticosteroid.ALT and AST of the control group were (140±22) U/L and (131±16) U/L respectively,that of 4-1BBmAb group were (98±14) U/L and (89±11) U/L respectively.The ALT and AST of the glucocorticosteroid treatment group were (76±11) U/L and (71±10) U/L respectively,ALT was (61±8) U/L and AST was (55±7) U/L in the combination treatment group.Differences among groups was statistically significant (P＜0.01).The expression of CD4+CD25+T lymphocytes was (3.0±0.8)％ in the control group,(8.5±2.9)％ in the gluco-corticosteroid treatment group,(8.4±3.5)％ in the 4-1BBmAb treatment group and was (11.2±3.5)％ in the combination treatment group.The difference was significant among the groups (P＜0.05).Conclusion 4-1BB-mAb have therapeutic effect for hepatic injury.The effectiveness will become even more evident when 4-1BB monoclonal antibodies are used together with glucocorticosteroid.During the course of treatment,4-1BBmAb and glucocorticosteroid can impact the expressions of CD4+CD25+T lymphocytes and this is the mechanism for the effectiveness in treating immune-mediated hepatic injury.

Objective To test plasma levels of uPA,uPAR,D-dimer,IL-6 and TNF-α,and observe the relationships between uPA,uPAR and D-dimer,IL-6,TNF-αin patients with SIRS.Methods A prospective,clinical case-control study was adopted.Cases were collected from our hospital in January 2008 to January 2010,and all were ＞ 55 years of age.Venous blood samples were collected via routine venipuncture.Eighty-five patients were divided into two groups according to diagnostic criteria of SIRS:SIRS group collected from Intensive Care Unit ( n =50) and non SIRS group collected from medical ward ( n =35).The control group comprised 30 unrelated healthy blood donors who visited the General Health Checkup Division at our hospital.Patients with (1) pregnant women; (2) cancer; (3) died after admitted into ICU in 7 days; (4) after cardiopulmonary resuscitation ; ( 5 ) with previous blood system diseases; (6) patients with SIRS before admitted into ICU were excluded from the study.uPA,uPAR,D-D,IL-6 and TNF-α in blood were detected by commercial enzyme-linked immunosorbent assay (ELISA) kits.The data was analyzed using SPSS version17.0.Data accorded with normal distribution of measurement was expressed as mean ± standard,and analyzed by independent-samples t test; non-normal distribution of measurement data,expressed by median,was analyzed with Mann-Whitney test.Relationships between plasma levels of uPA,uPAR and D-dimer,IL-6 TNF-α were analyzed using Spearman rank correlation test.To compare with blood level of uPA,uPAR,IL-6 and TNF-α in SIRS patients in the application of diagnostic value of MODS,we constructed the receiver operating characteristic curve ( ROC curve) for blood levels of uPA,uPAR,IL-6 and TNF-α in 24 h.Results The plasma levels of uPA,uPAR,D-dimer,IL-6 and TNF-αin patients of SIRS were obviously higher compared with non-SIRS and normal controls ( all P ＜ 0.01 ).Correlation analysis showed that there was positive correlation between uPAR level and IL-6 level (r =0.395,P =0.004) ; there was positive correlation between uPAR level and TNF-αlevel ( r =0.606,P ＜0.01 ).There was no correlation between uPAR levd and D-dimer level ( r =- 0.069,P =0.632).There was no correlation between uPA level and D-dimer,IL-6 or TNF-α ( all p ＞ 0.05).There ROC curve were made based on the abilities of uPAR,D-dimer,IL-6 and TNF-αlevels in 24 hours to diagnose MODS,and the ROC areas under the curves were 0.76,0.58,0.86,0.83 respectively.Conclusions These results demonstrate that uPA and uPAR play a major contributory role in patients with SIRS in the process of coagulation disorders,but the mechanism in SIRS is not the same.uPAR may play a central rolein the development of SIRS to MODS.

There were 482 male patients with non-hyperostosis diagnosed by X-ray among 1207 males who visited West China Hospital because of pain and/or numbness in bone or/and in joints from August 2003 to December 2005; the base-line information in records included age, stature, body weight(calculated BMD, symptoms, co-morbidities, exercise frequency, and smoking. The bone mineral density of lumbar spine was determined and used to judge osteoporosis or non-osteoporosis. Comparison was made on the basic information between osteoporosis group and non-osteoporosis group by t test or chi2 test statistical analysis; the relationship of multiple factors with osteoporosis was analyzed by Logistic Regression. The results of comparison between osteoporosis group and non-osteoporosis group indicated, there were significant differences among BMI, exercise and smoking, but no significant differences were seen among age, complications of hypertension and diabetes mellitus. According to the results of multiple regression analysis, BMI and smoking are the risk factors of osteoporosis, yet exercise is the protection factors of osteoporosis; the risk of osteoporosis increases by 0.654 times in men with BMI scaling up by 1 kg/m2 (P = 0.004). Therefore, we conclude that BMI is a risk factor of osteoporosis in male, and it may be related to body fat distribution.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Child ; China ; epidemiology ; Exercise ; Humans ; Male ; Middle Aged ; Osteoporosis ; epidemiology ; etiology ; Prevalence ; Risk Factors ; Smoking ; Young Adult

From among the patients who visited the Dept. of Rehabilitation of West China Hospital for arthalgia in the period from Aug. 2003 to Dec. 2005, we recruited 566 male patients who were over 40 years of age and did not have hyperostosis in the lumbar spine, and whose T scores were each less than--1. Their ages ranged from 40 to 93 years, and the average age was 62.93 +/- 13.50. The dual-energy X-ray absorptiometry from DMS Company in France was used to measure the bone density of the L2-4 anterior-posterior. The basic data about the subjects, containing the age, height, weight, diabetes mellitus, exercise and smoking or not, were recorded. Then the body mass index were calculated. In accordance to the T score, the subjects were separated into two groups: osteopenia group and osteoporosis group. In comparison of the basic data between groups, BMI of osteoporosis group was significantly higher than that of the osteopenia group, but the number of the subjects who exercised was smaller (P < 0.05). Multiple linear regression analysis revealed that in the case BMI increased by 1 kg/m2, BMD significantly decreased by 0.003 g/cm2 (P = 0.002), and the age negatively correlated with BMD (B = -0.001, P = 0.035). "Exercise or not" was positively related to BMD (B = 0.028, P = 0.000). "Smoking or not" and BMD were not significantly correlated (P = 0.837). In conclusion, increase of BMI, or we may say, increase of fat, would decrease the lumbar spine average BMD in the patients of osteoporosis or osteopenia. Some reports have pointed out that only by increasing BMI with increased amount of muscles, but not with increased amount of fat, would be beneficial to the prevention of osteoporosis. So we concluded that the muscle amount in the subjects should be taken into account when we probe into the relation between BMI and BMD.
Adult ; Aged ; Aged, 80 and over ; Body Composition ; Body Mass Index ; Bone Density ; Bone Diseases, Metabolic ; metabolism ; Humans ; Lumbar Vertebrae ; metabolism ; Male ; Middle Aged ; Osteoporosis ; metabolism

Previous case-control studies have shown various degrees of inverse correlation between osteoarthritis (OA) and osteoporosis (OP). The aim of this study was to examine the relationship between osteophytes at the cervical , lumbar vertebrae and knee, and the bone mineral density (BMD) of lumbar spine. We analyzed the data on 4091 female patients (aged 13 to 92 years). Osteophyte was defined by X ray examination. BMD of the lumbar spine (LS) was measured by dual energy X-ray absorptiometry (Lunar DPX). The association of osteophytes with BMD and osteophytes at different sites and different degrees were assessed by covariance analysis. Adjustments were made for age and body mass index. The relationship between osteophytes and BMD was analyzed by Binary Logistic Regression. BMD at each site was greater in the female with osteophytes (L4 BMD: P < 0.01, Mean BMD: P < 0.05); the relationship between osteophytes and osteoporosis and that between duration of osteophytes and osteoporosis were inversely correlated (P < 0.01). It confirms the existence of an inverse relationship between osteophytes and OP while a positive relationship is between age, body mass index and osteoporosis.
Absorptiometry, Photon ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Density ; Female ; Humans ; Lumbar Vertebrae ; metabolism ; pathology ; Middle Aged ; Osteophyte ; metabolism ; Osteoporosis ; metabolism ; Young Adult