[Efficacy of polyetheretherketone rod hybrid surgery in preventing proximal junctional failure after adult spinal deformity surgery].

Objective: To investigate the clinical outcome and preventive effect of polyetheretherketone(PEEK) rod hybrid surgery on proximal junction failure(PJF) after long-segment fusion of adult spinal deformity. Methods: A retrospective study was conducted to analyze patients with degenerative scoliosis/kyphosis who underwent long-segment decompression and fusion surgery at Department of Orthopedics, Peking University First Hospital from January 2017 to December 2021. A total of 75 patients were included in the study, including 14 males and 61 females, aged (67.2±6.8)years (range:55 to 84 years). According to the operation method chosen by the patients, the patients were divided into PEEK rod hybrid group (20 cases) and traditional titanium rod group (55 cases). The general information of the patients was collected, and the coronal and sagittal parameters of the spine were measured before operation, at 1 month after operation, and at the last follow-up. The clinical effect of surgery was judged by the visual analogue scale (VAS) and Oswestry disability index (ODI). Whether proximal junctional kyphosis (PJK) and PJF occurred during the follow-up and the time of occurrence were recorded. Comparisons between groups were performed using independent sample t test, Mann-Whitney U test, χ2 test and Fisher's exact probability method. The data before and after surgery in the same group were compared using the paired sample t test and the Wilcoxon test. Results: There were no significant differences in age, gender, body mass index, bone mineral density, distal instrumented vertebrae, surgical segments, osteotomy method, operation time, and intraoperative bleeding between the two groups (all P>0.05). The follow-up time of the PEEK rod group was shorter(M(IQR)16.5(4.8) vs. 25.0(12.0),Z=-4.230,P<0.01). There were no significant differences in coronal, sagittal parameters, VAS and ODI between the two groups before operation (all P>0.05). Postoperative coronal Cobb angle, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, sagittal vertical axis (SVA), VAS and ODI were significantly improved in both groups(all P<0.05). At the last follow-up, the SVA of the PEEK rod hybrid group was(3.74±2.40)cm, which was significantly lower than that of the titanium rod group (6.28±4.06)cm (t'=-3.318, P=0.002). At the last follow-up, the ODI of the PEEK rod hybrid group was 30.7±6.1, significantly better than the titanium rod group 39.3±17.2(t=-3.203, P=0.046). PJK occurred in 2 patients (10.0%) in the PEEK rod hybrid group, and no PJF phenomenon was observed. In the titanium rod group, 18 patients (32.7%) developed PJK, and 11 patients (20.0%) developed PJF. There was a statistically significant difference in the incidence of PJF between the PEEK rod hybrid group and the titanium rod group (P=0.031). Conclusions: PEEK rod hybrid surgery can achieve good clinical results in the treatment of adult spinal deformities. Compared with traditional titanium rod surgery, it can significantly reduce the incidence of postoperative PJF and improve the clinical function of patients.

[Influence of antimicrobial peptide biofunctionalized TiO2 nanotubes on the biological behavior of human keratinocytes and its antibacterial effect].

Objective: To fabricate TiO2 nanotube material functionalized by antimicrobial peptide LL-37, and to explore its effects on biological behaviors such as adhesion and migration of human keratinocytes (HaCaT) and its antibacterial properties. Methods: The TiO2 nanotube array (NT) was constructed on the surface of polished titanium (PT) by anodization, and the antimicrobial peptide LL-37 was loaded on the surface of TiO2 nanotube (LL-37/NT) by physical adsorption. Three samples were selected by simple random sampling in each group. Surface morphology, roughness, hydrophilicity and release characteristics of LL-37 of the samples were analyzed with a field emission scanning electron microscope, an atomic force microscope, a contact angle measuring device and a microplate absorbance reader. HaCaT cells were respectively cultured on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of cell was observed by field emission scanning electron microscope. The number of cell adhesion was observed by cellular immunofluorescence staining. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Wound scratch assay was used to observe the migration of HaCaT. The above experiments were used to evaluate the effect of each group on the biological behavior of HaCaT cells. To evaluate their antibacterial effects, Porphyromonas gingivalis (Pg) was respectively inoculated on the surface of three groups of titanium samples. Each group had 3 replicates. The morphology of bacteria was observed by field emission scanning electron microscope. Bacterial viability was determined by live/dead bacterial staining. Results: A uniform array of nanotubes could be seen on the surface of titanium samples in LL-37/NT group, and the top of the tube was covered with granular LL-37. Compared with PT group [the roughness was (2.30±0.18) nm, the contact angle was 71.8°±1.7°], the roughness [(20.40±3.10) and (19.10±4.11) nm] and hydrophilicity (the contact angles were 22.4°±3.1° and 25.3°±2.2°, respectively) of titanium samples increased in NT and LL-37/NT group (P<0.001). The results of in vitro release test showed that the release of antimicrobial peptide LL-37 was characterized by early sudden release (1-4 h) and long-term (1-7 d) slow release. With the immunofluorescence, more cell attachment was found on NT and LL-37/NT than that on PT at the first 0.5 and 2.0 h of culture (P<0.05). The results of CCK-8 showed that there was no significant difference in the proliferation of cells among groups at 1, 3 and 5 days after culture. Wound scratch assay showed that compared with PT and NT group, the cell moved fastest on the surface of titanium samples in LL-37/NT group at 24 h of culture [(96.4±4.9)%] (F=35.55, P<0.001). A monolayer cells could be formed and filled with the scratch in 24 h at LL-37/NT group. The results of bacterial test in vitro showed that compared with the PT group, the bacterial morphology in the NT and LL-37/NT groups was significantly wrinkled, and obvious bacterial rupture could be seen on the surface of titanium samples in LL-37/NT group. The results of bacteria staining showed that the green fluorescence intensity of titanium samples in LL-37/NT group was the lowest in all groups (F=66.54,P<0.001). Conclusions: LL-37/NT is beneficial to the adhesion and migration of HaCaT cells and has excellent antibacterial properties, this provides a new strategy for the optimal design of implant neck materials.

[Analysis of pathogen distribution and drug resistance of acute,delayed and chronic periprosthetic joint infection].

Objective: To analyze the pathogen distribution and drug resistance in acute,delayed and chronic periprosthetic joint infection (PJI). Methods: The clinical data of 316 patients with periprosthetic infection after primary hip and knee arthroplasty admitted to the Department of Arthroplasty,the First Affiliated Hospital,Xinjiang Medical University from August 2010 to August 2020 were retrospectively analyzed.There were 146 males and 170 females,aged (62.3±14.2) years (range:22 to 89 years).One hundred and sixty one patients underwent total hip arthroplasty and 155 patients underwent total knee arthroplasty.According to the time of postoperative infection,the patients were divided into acute PJI group (65 cases),delayed PJI group (83 cases) and chronic PJI group (168 cases).The results of pathogen species,composition ratio and drug susceptibility tests were collected,and the independent sample t test,Chi-square test or Fisher's exact probability test were used for comparison. Results: Gram-positive bacteria were the main pathogens of PJI (49.7%,157/316),and the positive rates of culture in patients with acute PJI,delayed PJI and chronic PJI were 33.8% (22/65),55.4% (46/83) and 53.0% (89/168),and the difference was statistically significant(χ²=8.343,P=0.015).The common bacteria were coagulase-negative Staphylococcus (54.8%,86/157) and Staphylococcus aureus (30.6%,48/157),The drug-sensitivity to linezolid,vancomycin and tigacycline was 100%.The gram-negative bacteria were mainly Escherichia coli and Enterobacter cloacae,and the drug resistance rate to carbapenems was low,ranging from 0 to 9.09%.The drug resistance rates of acute PJI patients to rifampicin,ciprofloxacin and erythromycin were significantly higher than those of late onset and chronic PJI patients,the difference was statistically significant(rifampicin:χ²=14.332,P=0.001;ciprofloxacin:χ²=12.086,P=0.002;erythromycin:χ²=9.096,P=0.010);The drug resistance rate of acute PJI patients to levofloxacin,clindamycin and tetracycline was higher than that of chronic PJI patients,and the difference was statistically significant(levofloxacin:χ²=10.500,P=0.002; clindamycin: χ²=7.103,P=0.007; tetracycline: χ²=6.909,P =0.012).The resistance rate of ampicillin/sulbactam in acute PJI (60.0%) was significantly higher than that in chronic PJI (16.7%),and the difference was statistically significant(χ²= 5.853,P=0.040). Conclusion: Gram-positive bacteria are the main pathogens of PJI,and the resistance rate of pathogens of acute PJI is higher than that of late onset and chronic PJI.

[Clinical efficacy of short-term halo-pelvic traction combined with surgery in the treatment of severe spinal deformities].

OBJECTIVE: To evaluate the clinical efficacy of short-term halo-pelvic traction (HPT) combined with surgery in the treatment of severe spinal deformities. METHODS: In the study, 24 patients diagnosed as severe spinal deformity accepted the treatment of one-stage short-term HPT and two-stage surgery from January 2015 to May 2018 in our orthopedics department. 24 cases (9 males and 15 females) were retrospectively reviewed. The average age of the cohort was (28.8±10.0) years (12－48 years). The height, scoliosis angle, kyphosis angle, the height difference of shoulders, the height difference of crista iliaca, C7PL-CSVL and the perpendicular distance of S1 and the convex point of the patients were assessed at pre-traction, post-traction and post-surgery. The paired t test was used to analyze the difference among pre-traction, post-traction and post-surgery. RESULTS: The average traction time of 24 cases was (2.5±1.1) weeks (1－5 weeks). The height of pre-traction and post-traction were (141.7±11.2) cm (116-167 cm) and (154.1±9.5) cm (136－176 cm) respectively, showing significant difference (P < 0.05), and the increased height was (12.4±4.6) cm (4－20 cm). The average scoliosis angle before traction was 104.9°±35.0°(25°ï¼158°), and it was significantly decreased in post-traction[64.8°±21.0°(19°ï¼92°)] and post-surgery[39.3°±17.0° (10°-70°)] (P < 0.05). The traction's coronal correction rate was 37.2%±10.9% (11.9%－51.2%) and the total coronal correction rate was 61.9%±12.6%(26.9%-79.0%). The average kyphosis angle before traction was 106.9°±29.2°(54°ï¼163°), and it was significantly decreased in post-traction [63.1°±17.1°(32°ï¼92°)] and post-surgery [39.0°±16.8°(10°ï¼68°)](P < 0.05). The traction's sagittal correction rate was 40.0%±10.7%(16.7%－55.5%) and the total sagittal correction rate was 64.3%±10.7%(49.0%－87.5%). The average C7PL-CSVL before traction was (3.2±2.8) cm, and it was significantly decreased in post-traction [(2.5±2.5) cm] (P < 0.05). The perpendicular distance of S1 and the convex point before traction was (10.5±4.8) cm, and it was significantly decreased in post-traction[(8.4±3.5) cm] (P < 0.05). CONCLUSION: The one-stage short-term HPT combined with two-stage surgery is a safe and effective procedure for severe spinal deformities. The clinical efficacy is satisfactory and the complication is relatively less.

[Efficacy evaluation of one-stage revision combined with intra-articular injection of antifungal agents in the treatment of chronic periprosthetic fungal infection].

Objective: To investigate the clinical effect of one-stage revision combined with intra-articular injection of antifungal agents in the treatment of chronic periprosthetic fungal infection. Methods: A retrospective analysis of 11 patients(4 hips, 7 knees) admitted with chronic periprosthetic fungal infection at Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2004 to April 2016.There were males and females with an age of 67 years (range:47-77 years). Each patient underwent single-stage revision including aggressive soft-tissue debridement. Liquid samples and tissue samples were immediately sent to the microbiology laboratory for drug sensitivity testing and histological analysis. Removed the infected components and cement thoroughly, pouring powdered vancomycin into the medullary cavity and direct intra-articular injection of fungussensitive antibiotics. The patients with infected hips received an uncemented prosthesis and 0.5 g of gentamicin loaded commercial cement was received by the patients with infected knee.After that, a new prosthesis was implanted.Long-term combination therapy of antibacterial agents and antifungal agents were given after operation. Recurrence of infection and clinical outcomes were evaluated. The follow-up period was 5 years (range: 2-12 years). Results: One patient died of acute heart failure on the eighth postoperative day.Three infection cases were recurred.Eight cases had satisfactory outcomes and required no additional surgical or medical treatment for recurrence of infection. The Harris hip score assessed preoperatively and at latest follow-up was increased from 39.25±5.12 to 79.50±4.79, the difference was statistically significant (t=-11.356, P=0.001).The Hospital for Special Surgery knee score was improved from preoperative 46.25±5.61 to final follow-up 80.50±5.06, and the difference was statistically significant (t=-9.930, P=0.002). Conclusion: Treatment of chronic fungal periprosthetic joint infection with single-stage revision can be fairly effective for achieving acceptable functional outcomes.

[Effect of total hip arthroplasty in patients with stiff hip and severe length discrepancy].

Objective: To observe the outcomes of total hip arthroplasty in patients with stiff hip and moderate or severe leg length discrepancy and to explore the strategy for balance recovery. Methods: A retrospective review was conducted on the clinical data of 30 patients who had stiff hip and moderate or severe leg length discrepancy treated with unilateral primary total hip arthroplasty at Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University from January 2014 to January 2017.There were 18 male and 12 female patients aging of (43.5±9.7)years (range, 30-68 years). All patients had different degrees of pelvic tilt and scoliosis. In operation, contractured soft tissues were released, periarticular osteophytes were removed thoroughly and the center of ratation was restablished without femoral shortening osteotomy.Patient satisfaction, Harris hip score, perceived leg length discrepancy (LLD), true LLD and functional LLD were collected.Data were analyzed by paired-samples t-test. Results: The mean follow-up duration was (17.6±7.6)months (range, 12-30 months). The Harris hip score was improved from 37.6±5.7 preoperatively to 84.3±5.2 at last follow-up (t=-57.54, P=0.000). The preoperative and last follow-up data of true LLD((3.19±0.82)cm vs.(0.70±0.71)cm), functional LLD((4.36±1.72)cm vs.(0.46±0.53)cm) and perceived LLD((7.74±2.01)cm vs.(0.98±0.79)cm) was significantly difference(t=26.47, t=15.05, t=26.9, P<0.01). Twenty-seven patients were restored to normal level (LLD≤10 mm ) and there was no sciatic nerve injury observed after surgery. 90.0% (27/30) patients were satisfied by the outcome. Conclusions: Total hip arthroplasty have satisfactory effect in correcting leg-length discrepancy of stiff hip patients. Preoperative assessment, individualized surgical methods and soft tissue releasing are important for balance recovery of affected limbs.

Azithromycin influences airway remodeling in asthma via the PI3K/Akt/MTOR/HIF-1α/VEGF pathway.

Asthma is a respiratory disease that affects people of all walks of life, and is a hotspot of continuous research, with significant manpower and resources invested in its study. Airway remodeling is an important associated pathological change, and a mark of the irreversible damage produced by asthma. It involves compositional and functional changes in the cells of the airway walls, leading to reversible structural changes, and complicating treatment. Airway remodeling is mediated by different inflammatory pathways which have been targeted for treatment, with good results. However, given its complexity, systematic study of the pathogenesis of airway remodeling is still needed, and additional targeted therapies are necessary. Macrolide drugs, such as erythromycin, azithromycin, and clarithromycin, have antibacterial effects and also influence the cytokine secretion of macrophages and T-lymphocytes. They have direct effects on a variety of cytokines, inhibiting inflammation and reducing airway reactivity. In this study, we investigated the protective effect of azithromycin on airway remodeling through the phosphoinositol-3 kinase/Akt/mechanistic target of rapamycin kinase/hypoxia-inducible factor 1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. We observed that a long course of azithromycin could significantly reduce airway reactivity and ovalbulmin-induced pathological alterations in asthmatic mice. Gene expression analysis confirmed that HIF-1α and VEGF were significantly down-regulated following a long course of azithromycin administration.

MiR-26a protects type II alveolar epithelial cells against mitochondrial apoptosis.

OBJECTIVE: This study aims to investigate the miR-26a effects on H2O2-induced apoptosis of Type II alveolar epithelial cells (AEC-II) and the potential mechanism. MATERIALS AND METHODS: AEC-II cells were treated with 0.5 mmol/L H2O2 to mimic cellular model of acute lung injury. Transmitting electron microscopy (TEM) was employed to observe the change of morphological structures. After infecting with miR-26a mimics, flow cytometry was performed to detect cell apoptosis. Western blot was also done to explore mitochondrial apoptosis-related markers: Caspase-3, B-cell lymphoma-2 (Bcl-2) and Bax. AEC-II cells treated with 0.5 mmol/L H2O2 exhibited significant cell apoptosis. Overexpression using miR-26a mimics partially reversed the effects of H2O2-induced apoptosis in AEC-II cells, evidenced by flow cytometry results. RESULTS: Further Western blot results revealed increased levels of Caspase-3 and Bax, and the decreased Bcl-2 level after infecting with miR-26a mimics, indicating miR-26a has protective effects against mitochondrial apoptosis in AEC-II cells. CONCLUSIONS: MiR-26a protected AEC-II cells against apoptosis via mitochondrial pathway. Thus, miR-26a promises to be a potential therapy in treatment of Acute Respiratory Distress Syndrome (ARDS).

[Influence of patellofemoral joint degeneration on outcome of medial unicompartmental knee arthroplasty].

Objective: To evaluate the influence of patellofemoral joint degeneration and pre-operative pain location on the outcome of medial Oxford unicompartmental knee arthroplasty (UKA). Methods: A total of 58 patients (58 knees) with medial Oxford UKA had been performed for medial osteoarthritis from March 2013 to July 2014 in Department of Orthopaedic Surgery at First Teaching Hospital of Xinjiang Medical University were retrospective reviewed. There were 24 males and 34 females, the age from 43 to 87 years with the mean age was 68.5 years. The mean body mass index was 25.2 kg/m(2) ranging from 19.7 to 31.5 kg/m(2). Patients were divided into anterior-medial pain group (35 knees), anterior knee pain group (17 knees) and general knee pain group (6 knees) according to pre-operative pain location. Pre-operative radiological statuses of the patellefemoral joint were defined by Ahlback system and divided into patellofemoral joint degeneration group (16 knees) and normal group (42 knees). Patients were also divided into medial patellofemoral degeneration group (20 knees), lateral patellofemoral degeneration group (12 knees) and normal group (26 knees) according to Altman scoring system. Outerbridge system was used intraoperatively and the patients were divided into patellofemoral joint degeneration group (21 knees) and normal group (37 knees). Pre- and post-operative outcomes were evaluated with Oxford Knee Score (OKS), Western Ontario and MacMaster (WOMAC) and patellofemoral score system of Lonner. T test and ANOVA were used to analyze the data. Results: The average duration of follow-up was 33 months (from 26 to 42 months). There were no patients had complications of infection, deep vein thrombosis, dislocation or loosing at the last follow-up. Compared to pre-operation, OKS (18.9±3.5 vs. 38.9±4.7, 19.3±4.2 vs. 39.6±4.6, 18.1±3.2 vs. 38.1±3.7)(t=5.64 to 7.08, all P<0.01) and WOMAC (10.9±2.3 vs.53.2±4.5, 10.4±2.1 vs.54.6±3.4, 11.7±1.8 vs.52.8±3.7)(t=14.50 to 19.16, all P<0.01) decreased, and the Lonner score (88.9±3.4 vs.38.6±2.8, 87.5±4.1 vs.38.2±2.3, 88.2±3.2 vs. 37.6±3.5)(t=-19.78 to -18.16, all P<0.01) increased significantly in anterior-medial pain group, anterior knee pain group and general knee pain group. According to Ahlback scoring system, compared to pre-operation, OKS (18.3±2.4 vs. 38.7±4.4, 19.6±1.8 vs. 38.4±3.1)(t=7.05, 9.08, both P<0.01) and WOMAC (10.6 ±2.6 vs.53.2±4.5, 12.1±1.4 vs.52.4±3.3)(t=14.21, 19.52, both P<0.01) decreased, the Lonner score (88.1±3.1 vs.38.3±3.3, 86.9±2.6 vs.39.1±2.4)(t=-18.90, -23.40, both P<0.01) increased significantly in patellofemoral joint degeneration group and normal group, the outcomes were the same according to Altman and Outerbridge scoring system. There was no significant difference between patellofemoral joint degeneration group and normal group based on Ahlback grading system. According to Altman classification, compared to normal group, there was no statistically differences in OKS, WOMAC and Lonner scoring system between patients with degeneration in the medial patellofemoral joint group, OKS and WOMAC increased (20.2±1.4 vs.18.2±2.7, 12.5±1.7 vs.10.5±2.5) (t=-4.30, P=0.03; t=-4.80, P=0.02), the Lonner score decreased (84.3±2.8 vs.87.4±3.2) (t=-6.20, P=0.01) in lateral patellofemoral degeneration group. According to Outerbridge scoring system, there were no statistically differences in patients in patellofemoral joint degeneration group and normal group. Conclusions: There is a good evidence that neither mild to moderate degree of patellofemoral joint degeneration nor pre-operative pain location will compromise the short-term outcome of medial Oxford UKA, and should not be considered as contraindications. The situation is less clear for lateral patellofemoral degeneration, and more cautious option is advised.

[Analysis of prognostic factors of portal hypertension treated with devascularization].

Objective: To explore the prognostic factors of portal hypertension treated with devascularization. Methods: A total of 397 patients with portal hypertension underwent devascularization in Nanjing Drum Tower Hospital from February 1993 to April 2014, among which there were 242 male and 155 female patients with median age of 48 years. The perioperative data were retrospectively collected. Logistic regression was used to find the risk factors which affect the operative complications. Follow-up evaluation was in progress regularly. Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to find out factors which affect the long-term results. Results: All together 397 patients underwent devascularization, in whom 8 patients died perioperative, 389 patients discharged successfully. Logistic regression showed that age (≥48 years) (χ2=4.559, OR=2.048, P=0.033), red color sign before surgery (χ2=4.959, OR=2.129, P=0.026) and without portosystemic collateral vessels reserved (χ2=13.348, OR=5.122, P=0.000) were risk factors of perioperative complications. The follow-up time was (5.7±4.6) years. Totally 27 patients were lost from follow-up, 103 patients died for the disease during follow-up. The survival rate at 1-, 3-, 5-, 10-, 15- and 20-years was 93.6%, 86.9%, 80.1%, 59.3%, 54.1% and 38.5% respectively.Univariate analysis showed that gender (male), age (≥48 years), hemorrhage before surgery (≥500 ml per time), hepatitis virus and without portosystemic collateral vessels reserved were risk factors of the long-term survival (P<0.05). Cox regression analysis showed that age (≥48 years) (χ2=9.850, RR=1.904, P=0.002), hemorrhage before surgery (≥500 ml per time) (χ2=34.402, RR=3.273, P=0.000), hepatitis virus (χ2=7.573, RR=2.525, P=0.006) and without portosystemic collateral vessels reserved (χ2=5.905, RR=1.889, P=0.015) were independent risk factors that affect the long-term survival. Conclusion: Devascularization with portosystemic collateral vessels reserved has favorable perioperative and long-term outcome, and it definitely is a very safe and effective technique for portal hypertension.

[Salubrinal improves cardiac function in rats with heart failure post myocardial infarction through reducing endoplasmic reticulum stress-associated apoptosis].

OBJECTIVE: Endoplasmic reticulum (ER) stress plays an important role in ischemia-mediated cell death. The aim of the current study is to investigate the effects of salubrinal (Sal), a selective eIF2a dephosphorylation inhibitor, on heart failure rats and related mechanisms. METHODS: Heart failure was induced by coronary artery ligation (MI) in adult male Sprague-Dawley rats. To ensure comparable MI sizes post coronary artery ligation on various groups, echocardiography examination was performed before and 30 minutes after ligation in MI groups. Then rats were randomly assigned to 4 groups: Sham group (n=12), MI group (n=10), MI plus vehicle injections group (DMSO group, n=12) and MI plus Sal injection group (Sal group, n=12). Sal (1 mg/kg) or DMSO was injected via the tail vein daily for the first 3 days (starting at 30 minutes after ligation of the left coronary artery), followed by subcutaneous injections twice per week for 8 weeks. Cardiac function was assessed by echocardiography and cell apoptosis assessed by flow cytometric analysis after 8 weeks. Protein and mRNA levels of ER stress markers were evaluated by immunohistochemistry and real time RT-PCR respectively. RESULTS: Eight weeks later, LVEF was significantly higher, while LVESD and LVEDD values were significantly lower in Sal group compared to MI and DMSO groups (all P<0.05); LV/BW ratio was significantly higher in MI group than in Sham group ((2.30±0.40) mg/g vs.(1.78±0.31) mg/g, P<0.05), which was significantly reduced in Sal group ((1.88±0.25) mg/g), but not in DMSO group((2.25±0.36) mg/g, P<0.05 vs. MI). In addition, flow cytometric analysis showed that Sal treatment significantly reduced apoptosis but not necrosis in post MI. Immunohistochemistry and real time PCR analysis showed that the myocardial protein and mRNA expression of ER stress markers were significantly lower in Sal group than in MI group, myocardial caspase-12 expression was significantly upregulated in MI group and significantly reduced by Sal treatment. CONCLUSIONS: Our results suggest that reduction of ER stress and myocardial apoptosis through inhibition of eIF2α dephosphorylation may serve as the potential mechanisms for the improved cardiac function and attenuated cardiac remodeling post Sal treatment in this heart failure rat model.

That which does not kill us makes us stronger--does Nietzsche's quote apply to islets? A re-evaluation of the passenger leukocyte theory, free radicals, and glucose toxicity in islet cell transplantation.

In clinical islet transplantation, isolated islets are embolized into the liver via the portal vein (PV); however, up to 70% of the islets are lost in the first few days after transplantation (i.e., too quickly to be mediated by the adaptive immune system). Part of early loss is due to instant blood-mediated inflammatory reaction, an immune/thrombotic process caused by islets interacting with complement. We have shown that glucose toxicity (GT) also plays a critical role based upon the observation that islets embolized into the PVs of diabetic athymic mice are rapidly lost but, if recipients are not diabetic, the islet grafts persist. Using donor islets resistant to the ß-cell toxin streptozotocin, we have shown that intraportal islets engrafted in non-diabetic athymic mice for as little as 3 days will maintain normoglycemia when streptozotocin is administered destroying the recipient's native pancreas ß-cells. What is the mechanism of GT in ß-cells? Chronic exposure to hyperglycemia over-exerts ß-cells and their electron transport chains leak superoxide radicals during aerobic metabolism. Here we reinterpret old data and present some compelling new data supporting a new model of early intraportal islet graft loss. We hypothesize that diabetes stimulates overproduction of superoxide in both the ß-cells of the islet grafts and the endothelial cells lining the intraportal microvasculature adjacent to where the embolized islets become lodged. This double dose of oxidant damage stresses both the islets, which are highly susceptible to free radicals because of inherent low levels of scavenging enzymes, and the adjacent hepatic endothelial cells. This, superimposed upon localized endothelial damage caused by embolization, precipitates inflammation and coagulation which further damages islet grafts. Based upon this model, we predict that pre-exposing islets to sub-lethal hyperoxia should up-regulate islet free radical scavenging enzyme levels and promote initial engraftment; reinterpretation of 30 years old "passenger leukocyte" data and preliminary new data support this. Other data suggests that pre-exposure of recipients to hyperoxia could up-regulate antioxidant enzymes in the hepatic endothelium. The combination of both effects could markedly enhance early intraportal islet graft survival and engraftment. Finally, if our model is correct, current in vitro and in vivo tests used to test batches of harvested islets for viability and function prior to transplantation are poorly conceived (n.b., it is already well-known that results using these tests often do not predict clinical islet transplantation success) and a different testing paradigm is suggested.

Long-term survival and function of intraportal porcine and human islet xenografts in nondiabetic nude mice.

Instant blood-mediated inflammatory reaction (IBMIR) is a serious obstacle to both clinical islet allotransplantation and future islet xenotransplantation via the portal vein. We have previously observed uniform long-term tilapia (fish) islet xenograft survival when islets were transplanted intraportally into nondiabetic nude mice (nDNM), but not in diabetic nude mice (DNM). In this study, we examined whether human islets (HI) and adult porcine islets (API) can tolerate intraportal transplantation into nDNM like tilapia islets. HI and API were transplanted intraportally into nDNM. Recipients were humanely killed either 14 or 28 days after transplantation and livers were processed for histology. Human insulin and human C-peptide were measured in the terminal serum samples of HI recipients. In six of seven HI and seven of seven API recipients, liver histology showed insulin-positive islet xenografts. In recipients with HI, the numbers of islets/ductal structures seen histologically correlated well with serum sample results. These results show that HI and API can survive and function long term after intraportal transplantation into nDNM recipients. Our previous and present data indicated that DNM and nDNM could be useful models to study "glucose toxicity" and the role of IBMIR in the fate of intraportal islet grafts.

beta2 Adrenoceptor gene single nucleotide polymorphisms are associated with rheumatoid arthritis in northern Sweden.

BACKGROUND: beta(2) Adrenoceptor (beta(2)-AR) represents a link between the sympathetic nervous system and the immune system, and may be involved in human rheumatoid arthritis (RA). The gene encoding beta(2)-AR contains three single nucleotide polymorphisms (SNPs) at amino acid positions 16, 27, and 164. OBJECTIVE: To examine the common variants at positions 16 and 27 and their association with RA. METHODS: An allele-specific polymerase chain reaction to determine the common variants at positions 16 and 27 was used in 154 patients with RA and 198 ethnically matched healthy subjects from northern Sweden. RESULTS: Carriage of Arg16 and of Gln27 was associated with RA. Carriage of Gln27 was associated with activity of the disease and in combination with non-carriage of Arg16 with higher levels of rheumatoid factor. CONCLUSION: The beta2-AR SNPs may thus constitute an additional non-major histocompatibility complex association in RA.

Unusual 1/r-dependent radiation intensity in any biaxial crystal.

Lighthill's prediction of an unusual 1/r-dependent radiation intensity from a small monochromatic source is found to exist in any homogeneous and lossless biaxial crystal along the two optical ray axes, where r is the radial distance from the source. This is a consequence of the special shape of the wave-vector surface on which there is, around each singular point of self-intersection (or "dimple"), a circular locus of points all having the same surface normal direction and thus sharing a common tangent plane. A heuristic derivation of the result is given and a simple optical experiment is proposed to detect such an unusual distance dependence.

[Quantitative study on tongue diagnosis in stroke patients].

OBJECTIVE: To study the tongue proper and tongue fur quantitatively in stroke patients. METHODS: Three hundred and seventy-eight stroke patients were studied by means of TCM Glossoscopy Expert System, the techniques of color digitized image processing and pattern recognition were applied to objectively study the changes of tongue proper and tongue fur. RESULTS: Dark-red tongue was the commonest tongue proper, which revealed in 128 cases (33.86%) in the 378 patients investigated. There was significant difference of red (R), green (G) and blue (B) values in dark-red tongue as compared with those in pale-purple tongue, pale-white tongue, pale-red tongue, deep red tongue, purple-red tongue and blue-purple tongue (P < 0.05, P < 0.01). Thick and yellow greasy fur was the commonest in 214 cases of acute stage, it accounted for 30.84% and with a total of 66 cases. There was also significant difference in R/G and R/B values among different types of tongue fur (P < 0.01). CONCLUSION: This quantitative study on stroke patients regarding to tongue proper and tongue fur by means of TCM Glossoscopy Expert System provides a base for standardization and quantification of diagnosis of stroke patients.

beta2-adrenergic receptor gene polymorphisms in myasthenia gravis (MG).

The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein coupled receptors and is present mainly on skeletal and cardiac muscle cells and lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population. The distribution of polymorphisms at amino acid positions 16, 27 and 164 is changed in asthma, hypertension and obesity. We have earlier reported a decreased density of the beta2-AR on peripheral blood mononuclear cells and the presence of beta2-AR antibodies in patients with MG. Since certain polymorphisms affect the function of the beta2-AR, it was of interest to analyse these in MG. Using allele-specific polymerase chain reaction amplification, we revealed an over-representation of homozygosity for Arg16 and a lower prevalence of homozygosity for Gly16 in MG patients compared with healthy individuals. The increased frequency of homozygosity for Arg16 was due to a contribution from patients with generalized MG but not from patients with only ocular disease. Homozygosity for Glu27 was negatively associated with both the presence of beta2-AR antibodies and severity of disease. Moreover, acetylcholine receptor (AChR) antibodies were more often present in patients being homozygous for Gln27. Our results imply that homozygosity for Arg16 confers susceptibility to generalized MG, and that certain polymorphisms at amino acid position 27 are associated with subgroups of patients.

Antibody dependent cell-mediated cytotoxicity--an additional mechanism in human autoimmune myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease characterised by serum anti-acetylcholine receptor (AChR) antibodies and several pathogenic mechanisms for the action of these antibodies have been elucidated. In this study, we have analysed a possible additional mechanism for these antibodies, namely antibody-dependent cell-mediated cytotoxicity (ADCC). Using as target cells a cell line expressing AChR, we could show an increased ADCC mediated by sera from MG patients. Sera with AChR antibodies induced a higher cytotoxicity than sera from patients without these antibodies or healthy individuals. Sera from MG patients with thymoma induced a higher cytotoxic effect than sera from other patients. There was a strong positive correlation between the concentration of AChR antibodies and cytotoxicity mediated by purified IgG fractions from thymoma patients. In addition, there was a higher cytotoxicity mediated by sera from thymoma patients with extended dinucleotide repeats, (AT)n repeats, in the CTLA-4 gene. ADCC mediated by AChR antibodies may thus be another possible pathogenic mechanism that could operate in MG patients, especially in patients with thymoma.