Objective To study the effect of blood biqing1 injection on patients with septic shock in peripheral blood red cell distribution width,inflammatory mediators and APACHEII score.Methods 90 patients with septic shock in our hospital from May 2014 to May 2015 were randomLy divided into observation group and control group,each of 45 cases,the control group was treated with conventional treatment of septic shock,blood in patients in the observation group on the basis of routine treatment of septic shock biqing1 injection,before and after comparison two groups of red cell distribution width and inflammatory mediators(IL-2,IL-4,IL-6)level and APACHEII score.Results Two groups of patients before treatment,IL-2,IL-4 and IL-6 levels compared to no difference after treatment,the observation group were IL-2,IL-4,IL-6 levels were(23.5±2.3),(21.7 ±3.6),(22.5±3.4),significantly lower than the control group patients,two groups of patients before treatment,red cell distribution width,APACHEII score comparison showed no difference in treatment of 2D two groups of patients after the red cell distribution width and APACHEII score compared to no difference after the treatment of 5D,observation group distribution in red blood cell width(％),APACHE II score were(9.8±1.7),(10.4±1.9),significantly lower than the control group patients,two groups were CO,CI,SVR,EVLWI compared to no difference before treatment.After the treatment of 2D patients in the two groups CO,CI,SVR,EVLWI compared to no difference after the treatment of 5 days patients in the observation group,CO,CI were(8.9±1.4),(9.3±2.1),significantly higher than the control group,while the level of SVR and EVLWI were(865±104.5),(5.7±0.9),significantly lower than the control group.Conclusion Will the blood injection can reduce septic shock in patients with peripheral blood red cell distribution width and the levels of inflammatory mediators,reduce the score of APACHEII.

In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 (cdk-5) inhibition in mice with Niemann-Pick disease type C (NPC) (npc(-/-)), recombinant adeno-associated virus (rAAV) carrying the small interfering RNA (siRNA) specific for cdk-5 gene was injected into 3-day-old npc(-/-) mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc(-/-) mice and non-surgery age-matched npc(-/-) mice were employed as controls (n=6-10/group). From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc(-/-) mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc(-/-) mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc(-/-) mice, and significantly attenuated the hyperphosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuroprotective effect on neurons in NPC mice.

Objective:To investigate the regulatory effect of miRNA-21-5p on peripheral blood B lymphocyte proliferation and apoptosis in systemic lupus erythematosus (SLE) patients by targeting program-med cell death protein 4 (PDCD4) .Methods:Thirty patients with SLE diagnosed clinically in our hospital were enrolled. Peripheral blood lymphocyte (PBL) was extracted by gradient centrifugation, and B cells were separated by magnetic beads. The proportion of B lymphocyte in peripheral blood was detected by flow cytometry. The cells were divided into five groups by electrotransfection: blank control group, miRNA-21-5p negative control (NC) group, miRNA-21-5p group and miRNA-21-5p inhibitor group, PDCD4 negative control group and PDCD4 siRNA group. Cells were collected 48 hours after transfection. The expression levels of miRNA-21 and PDCD4 were detected by real-time polymerase chain reaction (RT-PCR). Western blotting assay was used to detect the expression of PDCD4 in cells of each group. The targeting relationship between miRNA-21-5p and PDCD4 was verified by double luciferase target experiment. Flow cytometry was used to detect the apoptosis of cells in each group, and CCK-8 method was used to detect the proliferation of cells in each group. Western blotting and RT-PCR were used to detect the expression levels of Fas, FasL, CD40 and CD40L, respectively. Independent sample t test was used to compare the data between the two groups; single factor analysis of variance was used to analyze the results of multiple samples; chi square test was used to compare the positive rate of anti dsDNA antibody. Results:The levels of serum complement [C3 (0.85±0.11) g/L and C4 (0.54±0.09) g/L] in patients with SLE were lower ( t=7.524, P<0.05; t=38.471, P<0.05) than [C3 (1.16±0.17) g/L and C4 (1.57±0.09) g/L] in healthy controls. The levels of anti-dsDNA antibodies (47%), IgG(15.46±0.75) g/L, and IgA (2.68±0.20) g/L were increased than the levels of anti-dsDNA antibodies (17%), IgG (11.95±0.80) g/L, and IgA (2.16±0.11) g/L in healthy controls ( χ2=4.427, P<0.05; t=15.218, P<0.05; t=10.125, P<0.05). The proportion of B lymphocyte [(6.78±0.29)%] and the expression levels of miRNA21-5p (7.52±0.59) in peripheral blood of SLE patients was significantly higher than the proportion of B lymphocyte [(2.03±0.24)%] and the expression levels of miRNA21-5p (3.60±0.62) in healthy controls ( t=59.064, P<0.05; t=19.317, P<0.05), while the expression levels of PDCD4 gene (1.54±0.35) in peripheral blood of SLE patients was significantly lower than that (4.42±0.42) in healthy controls ( t=19.126, P<0.05). Compared with the blank control group and the miRNA-21-5p NC group, cell proliferation in the miRNA-21-5p Inhibitor group was inhibited, and the proportion of apoptotic cells increased ( F=5.244, P<0.05; F=37.903, P<0.05). Compared with the blank control group and PDCD4 NC group, cell proliferation in PDCD4 siRNA group was significantly enhanced, and apoptotic rate decreased ( F=5.956, P<0.05; F=25.431, P<0.05). The results of double luciferase reporter gene assay showed that PDCD4 is the target gene of miRNA-21-5p. Conclusion:miRNA-21-5p may promote the proliferation of peripheral blood B lymphocyte in SLE patients by inhibiting the expression of PDCD4, leading to abnormal lymphocyte apoptosis. miRNA-21-5p can be used as a new target gene for the treatment of systemic lupus erythematosus.

Objective: This study aimed to investigate the impact of polycystic ovary syndrome (PCOS) on fertility-sparing treatment in young patients with atypical endometrial hyperplasia (AEH) or endometrioid endometrial cancer (EEC). Methods: A total of 285 patients with EEC (n=76, FIGO stage IA, without myometrium invasion) or AEH (n=209) who received progestin-based fertility-sparing treatment were evaluated retrospectively. Among the 285 patients, 103 (36.1%), including 70 AEH cases and 33 EEC cases, were diagnosed with PCOS. General characteristics, cumulative 16- and 32-week complete response (CR) rate, pregnancy outcome and recurrence were compared between patients with or without PCOS. Results: The cumulative 16-week CR rate was lower in the PCOS group than in the non-PCOS group (18.4% vs. 33.8%, p=0.006). Patients with PCOS took longer treatment duration to achieve CR (7.0 months vs. 5.4 months, p=0.006) and shorter time to relapse after CR (9.6 months vs. 17.6 months, p=0.040) compared with non-PCOS group. After adjusting for patient age, body mass index, PCOS, homeostasis model assessment-insulin resistance index, and serum testosterone levels, we found that body mass index ≥25 kg/m2 (HR=0.583; 95% CI=0.365–0.932; p=0.024) and PCOS (HR=0.545; 95% CI=0.324–0.917; p=0.022) were significantly correlated with lower 16-week CR rate. Conclusion PCOS was associated with lower 16-week CR rate, longer treatment duration and shorter recurrence interval in patients with AEH or EEC receiving fertility-preserving treatment.

Objective To study the protective effect of quercetin on the kidney of mice with systemic lupus erythematosus (SLE) and to explore its effect on transforming growth factor (TGF)-β1 and monocyte chemoattractant protein-1 (MCP-1).Methods Thirty BALB/c female mice were randomly divided into control group,model group and drug group according to the envelope method,with 10 mice in each group.A mouse model of SLE was established by intra-peritoneal injection of pristane method.The drug group was given quercetin treatment,and the control group and the model group were given the same dose of normal saline.The renal function index and autoanti-body level in each group of mice were compared.The pathological changes of renal tissues were observed by HE staining.The expressions of TGF-β1 and MCP-1 were determined by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR).The renal function index,autoantibody level,TGF-β1,and MCP-1 expression were statistically analyzed by analysis of one-way analysis of variance (ANOVA).Results The levels of blood urea nitrogen (BUN),serum creatinine (Scr),24 h urine protein,kidney hypertrophy index,antinuclear antibody (ANA) antibody,anti-dsDNA antibody and anti-snRNP/Sm in the model group and the drug group were higher than those in the control group.Compared with the model group,the levels of BUN,Scr,24 h urine protein,kidney hypertrophy index,ANA antibody,anti-dsDNA antibody,anti-snRNP/Sm in the drug group were(11.3±1.1) mmol/L,(45±4) μmol/L,(25.7±2.6) mg/24 h,(4.3±0.4)×10-3,(30.3±3.1) ng/L,(472±48) μmol/L and (17.6±1.8) ng/L,which were decreased (q =10.678,6.698,14.948,14.412,9.226,4.691,8.226,P＜0.01).The glomerular score,tubulointerstitial score and tubulointer-stitial score of the model group were higher than those of the control group.The glomerular score,tubulointer-stitial score and tubular score of the drug group were lower than those of the model group (q=10.935,49.537,20.439,P＜0.01).HE staining showed that the kidney structure of the control group was no obvious damage.In the model group,the glomerular volume of the mice increased,and the inflammatory cells in the renal interstitial and renal tubules infiltrated.The pathological changes in the drug group were significantly reduced compared with the model group.Compared with the control group,the expression levels of TGF-β1,MCP-1 protein and mRNA in the model group and the drug group were significantly increased.Compared with the model group,TGF-β1 and MCP-1 protein and mRNA expression levels the mice in the drug group were significantly reduced.Conclusion Quercetin can improve renal function in mice with SLE by down-regulating the expression of TGF-beta 1 and MCP-1.

BACKGROUNDPatellofemoral osteoarthritis commonly occurs in older people, often resulting in anterior knee pain and severely reduced quality of life. The aim was to examine the effectiveness of arthroscopic patelloplasty and circumpatellar denervation for the treatment of patellofemoral osteoarthritis (PFOA).

METHODSA total of 156 PFOA patients (62 males, 94 females; ages 45-81 years, mean 66 years) treated in our department between September 2012 and March 2013 were involved in this study. Clinical manifestations included recurrent swelling and pain in the knee joint and aggravated pain upon ascending/descending stairs, squatting down, or standing up. PFOA was treated with arthroscopic patelloplasty and circumpatellar denervation. The therapeutic effects before and after surgery were statistically evaluated using Lysholm and Kujala scores. The therapeutic effects were graded by classification of the degree of cartilage defect.

RESULTSA total of 149 cases were successfully followed up for 14.8 months, on average. The incisions healed well, and no complications occurred. After surgery, the average Lysholm score improved from 73.29 to 80.93, and the average Kujala score improved from 68.34 to 76.48. This procedure was highly effective for patients with cartilage defects I-III but not for patients with cartilage defect IV.

CONCLUSIONSFor PFOA patients, this procedure is effective for significantly relieving anterior knee pain, improving knee joint function and quality of life, and deferring arthritic progression.

Aged ; Aged, 80 and over ; Cartilage, Articular ; innervation ; surgery ; Denervation ; methods ; Humans ; Knee Joint ; innervation ; surgery ; Middle Aged ; Osteoarthritis, Knee ; surgery ; Patellofemoral Joint ; innervation ; surgery ; Quality of Life

significantly attenuated the hyper-phosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuropro-tective effect on neurons in NPC mice.

Objective:To investigate the role of the clearance of exogenous myelin antigen in experimental autoimmune encephalomyelitis (EAE).Methods:EAE was induced in C57BL/6J mice by subcutaneous immunization with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) or FITC-MOG 35-55. The concentration of exogenous myelin antigen was assessed by analyzing the proliferation of the transferred CFSE-labeled mT/mG-2D2 CD4 + T cells in spleen tissues. The release of exogenous myelin antigen from the inoculation sites was analyzed by immunohistochemistry and flow cytometry. HE staining was used to investigate the mechanism underlying the rapid clearance of exogenous myelin antigen. The role of the clearance of exogenous myelin antigen in EAE was investigated by comparative analysis of EAE induced by subcutaneous immunization in the back and footpads, and analyzing the therapeutic effect of soluble MOG 35-55. Results:The proliferation of mT/mG-2D2 CD4 + T cells in mice was enhanced on day 2 than on day 7 after immunization [(52.6±6.8)% vs (18.5±4.9)%, P<0.01]. There was no significant difference in the proliferation of mT/mG-2D2 CD4 + T cells between EAE mice (day 13) and naive mice [(4.4±1.5)% vs (2.5±1.4)%, P=0.11]. Immunohistochemistry and flow cytometry showed that MOG 35-55 was released and engulfed by CD11b + cells at the inoculation sites, and no more MOG 35-55 was released at the onset of EAE. HE staining showed that granuloma that formed surrounding the antigen emulsion during EAE development prevented antigen release from the emulsion, completely isolating the antigen from the peripheral immune system. The incidence of EAE was relatively low in mice immunized via footpads, which was related to the sustained release of MOG 35-55, but had no direct relation to CD4 + regulatory T cells. Continuous intraperitoneal injection of soluble MOG 35-55 could prevent and treat EAE. Conclusions:Exogenous myelin antigen has been completely cleared in EAE mice, and the occurrence of EAE depends on the clearance of the myelin antigen.

BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.

BACKGROUND:Osteonecrosis is a common refractory disease in clinical practice,and observational studies have suggested that micronutrients may have a prognostic role in osteonecrosis.However,the specific causal association between micronutrients and osteonecrosis is not known. OBJECTIVE:To explore the causal association between micronutrients and osteonecrosis by Mendelian randomization using summary data from a large population-based genome-wide association study(GWAS)for clinical diagnosis and treatment. METHODS:The required exposure and outcome data(calcium,magnesium,iron,vitamin E,carotenoids,retinol&osteonecrosis)were extracted from the IEU OpenGWAS database,GWAS catalog database,and FinnGen database.Data were analyzed by bidirectional Mendelian randomization with inverse-variance weighted as the primary study method,and weighted median method,simple mode method,weighted mode method,and MR-Egger regression to complement the results.The reliability of the data was then verified through sensitivity analyses. RESULTS AND CONCLUSION:(1)The results found a positive correlation between serum iron concentration and osteonecrosis,while no correlation was found for other micronutrients.There was no reverse causality in all the data.(2)The results of sensitivity analysis showed a robust causality.(3)By Mendelian randomization method,this study provided evidence of causality between serum iron concentration and osteonecrosis,and understanding the causality of micronutrient elements on osteonecrosis can help in the clinical diagnosis and treatment of osteonecrosis,which is of great clinical significance.