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Guan-Nan He, Na-Ren Bao, Shuang Wang, Man Xi, Tian-Hao Zhang, Feng-Shou Chen Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, People’s Republic of ChinaCorrespondence: Feng-Shou ChenDepartment of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, People’s Republic of ChinaEmail shouyongpang4540@163.comBackground: Liver cancer ranks the top four malignant cancer type worldwide, which needs effective and safe treatment. Ferroptosis is a novel form of regulated cell death driven by iron-dependent lipid peroxidation and has been regarded as a promising therapeutic target for cancers. In this work, we aimed to study the effects of anesthetic ketamine on proliferation and ferroptosis of liver cancer.Methods: Cell viability and proliferation were detected by cell counting kit 8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EdU) assay. Ferroptosis was determined by levels of Fe2+, lipid reactive oxygen species (ROS), and malondialdehyde (MDA). RNA levels of lncPVT1, miR-214-3p, and glutathione peroxidase 4 (GPX4) were checked by real-time PCR assay. Clinical liver tumor samples were collected to detect the levels of long noncoding RNA lncPVT1, miR-214-3p, and GPX4, and their correlation was evaluated by Pearson comparison test. Luciferase reporter gene assay and RNA pulldown were conducted to determine the binding between lncPVT1, miR-214-3p, and GPX4 3ʹUTR.Results: Ketamine significantly suppressed viability and proliferation of liver cancer cells both in vitro and in vivo, as well as stimulated ferroptosis, along with decreased expression of lncPVT1 and GPX4. LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of live cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. Ketamine-induced cell growth suppression and ferroptosis were also suppressed by miR-214-3p inhibition and GPX4 overexpression.Conclusion: In this work, we determined that ketamine suppressed viability of liver cancer cells and induced ferroptosis and identified the possible regulatory mechanism of lncPVT1/miR-214-3p/GPX4 axis.Keywords: liver cancer, ketamine, lncPVT1, miR-214-3p, GPX4

Objective: To investigate the opportune time of secondary definitive surgery for patients with multiple injuries from earthquakes based on the acute physiology and chronic health evaluation II (APACHE II) score and the principles of damage control.Methods: Twenty-one patients with critical earthquake injuries were treated with damage control strategies, followed by medical support and surgical intervention to restore their physical potential in the intensive care unit (ICU). Successive APACHE II scoring was adopted to evaluate the patients'physiological status, and then, internal fixation of fractures and other definitive operations were performed.Results: All the patients were effectively treated with few complications, low deformity rate and no death.Conclusions: Appropriate evaluation of patients?physiological potential, right decision on surgical time and proper operative method can reduce the rates of complications, disability and death for patients with critical earthquake injuries. [ABSTRACT FROM AUTHOR]

Chronic rotator cuff injuries (CRCIs) still present a great challenge for orthopaedics surgeons. Many new therapeutic strategies are developed to facilitate repair and improve the healing process. However, there is no reliable animal model for chronic rotator cuff injury research. To present a new valuable rat model for future chronic rotator cuff injuries (CRCIs) repair studies, and describe the changes of CRCIs on the perspectives of histology, behavior and MRI. Sixty male Wistar rats were enrolled and underwent surgery of the left shoulder joint for persistent subacromial impingement. They were randomly divided into experimental group (n = 30, a 3D printed PEEK implant shuttled into the lower surface of the acromion) and sham operation group (n = 30, insert the same implant, but remove it immediately). Analyses of histology, behavior, MRI and inflammatory pain-related genes expression profiles were performed to evaluate the changes of CRCIs. After 2-weeks running, the rats in the experimental group exhibited compensatory gait patterns to protect the injured forelimb from loading after 2-weeks running. After 8-weeks running, the rats in the experimental group showed obvious CRCIs pathological changes: (1) acromion bone hyperplasia and thickening of the cortical bone; (2) supraspinatus muscle tendon of the humeral head: the bursal-side tendon was torn and layered with disordered structure, forming obvious gaps; the humeral-side tendon is partially broken, and has a neatly arranged collagen. Partial fat infiltration is found. The coronal T2-weighted images showed that abnormal tendon-to-bone junctions of the supraspinatus tendon. The signal intensity and continuity were destroyed with contracted tendon. At the nighttime, compared with the sham operation group, the expression level of IL-1β and COX-2 increased significantly (P = 0063, 0.0005) in the experimental group. The expression of COX-2 in experimental group is up-regulated about 1.5 times than that of daytime (P = 0.0011), but the expression of IL-1β, TNF-a, and NGF are all down-regulated (P = 0.0146, 0.0232, 0.0161). This novel rat model of chronic rotator cuff injuries has the similar characteristics with that of human shoulders. And it supplies a cost-effective, reliable animal model for advanced tissue engineered strategies and future therapeutic strategies., (© 2024. The Author(s).)

Hydrogen (H 2 ) has been widely used in the chemical industry as a reducing agent. As the researches move along, increasing attention has been paid to its biological functions. The selective antioxidant effect of hydrogen is considered to be the main reason for medical applications. So far, many studies have confirmed its potential protective effects on ischemia/reperfusion injury of multiple organs, neurodegenerative diseases, bone and joint diseases, and respiratory diseases, opening a new era in the medical research and application of H 2 . Increasing studies have focused on its biological effects and molecular mechanisms in the treatment of different diseases. In this paper, we review the biological effects, molecular mechanisms and methods of H 2 supply. We do hope that the advances in materials science can be better translated into medical applications and solve clinical problems. The medical application of H 2 is promising, and how to prepare an H 2 sustained-release system to achieve a sustained and stable H 2 supply in the body and ultimately improve the therapeutic effect of H 2 is a problem worthy of further investigation., Competing Interests: None

Background and Aims: Rotator cuff tendinopathy is common and is related to pain and dysfunction. However, the pathological mechanism of rotator cuff injury and shoulder pain is unclear. Objective: to investigate the pathological mechanism of rotator cuff injury and shoulder pain, and screen out the marker proteins related to rotator cuff injury by proteomics., Methods: Subacromial synovium specimens were collected from patients undergoing shoulder arthroscopic surgery. The experimental group were patients with rotator cuff repair surgery, and the control group were patients with habitual dislocation of the shoulder joint. Pathological examination was performed, and then followed by non-labeled quantitative proteomic detection. Finally, from analysis of the biological information of the samples, specific proteins related to rotator cuff injury and shoulder pain were deduced by functional analysis of differential proteins., Results: All the patients in experimental groups were representative. A large number of adipocytes and inflammatory cells were found in the pathological sections of the experimental group; the proteomics analysis screen identified 80 proteins with significant differences, and the analysis of protein function revealed that S100A11 ( p  = 0.011), PLIN4 ( p  = 0.017), HYOU1 ( p  = 0.002) and CLIC1 ( p  = 0.007) were closely related to oxidative stress and chronic inflammation., Conclusion: Rotator cuff injury is closely related to oxidative stress and chronic inflammatory response, and the results suggest that the expression of S100A11, PLIN4, HYOU1 and CLIC1 in the synovium of rotator cuff injury provides a new marker for the study of its pathological mechanism., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Objectives: As promising alternative to current metallic biomaterials, the porous Mg scaffold with a 3-D open-pore framework has drawn much attention in recent years due to its suitable biodegradation, biocompatibility, and mechanical properties for human bones. This experiment's aim is to study the mechanical properties, biosafety, and osteogenesis of porous Mg-Zn alloy., Methods: A porous Mg-2Zn-0.3Ca (wt%) alloy was successfully prepared by infiltration casting, and the size of NaCl particles was detected by a laser particle size analyzer. The microstructure of the Mg-2Zn-0.3Ca alloy was characterized by the stereoscopic microscope and Sirion Field emission scanning electron microscope. X-ray computerized tomography scanning (x-CT) was used to create the 3-D image. The degradation rate was measured using the mass loss method and the pH values were determined together. The engineering stress-strain curve, compressive modulus, and yield strength were tested next. The bone marrow stromal cells (BMSC) were cultured in vitro. The CCK-8 method was used to detect the proliferation of the BMSC. Alkaline phosphatase (ALP) and alizarin red staining were used to reflect the differentiation effects. After co-culturing, cell growth on the material's surface was observed by scanning electron microscope (SEM). The cell adhesion was tested by confocal microscopy., Results: The obtained results showed that by using near-spherical NaCl filling particles, the porous Mg alloy formed complete open-cell foam with a very uniform size of pores in the range of 500-600 μm. Benefitting from the small size and uniform distribution of pores, the present porous alloy exhibited a very high porosity, up to 80%, and compressive yield strength up to 6.5 MPa. The degradation test showed that both the pH and the mass loss rate had similar change tendency, with a rapid rise in the early stage for 1-2 day's immersion and subsequently remaining smooth after 3 days. In vitro cytocompatibility trials demonstrated that in comparison with Ti, the porous alloy accelerated proliferation in 1, 3, 5, and 7 days (P < 0.001), and the osteogenic differentiation test showed that the ALP activity in the experimental group was significantly higher (P = 0.017) and has more osteogenesis nodules. Cell adhesion testing showed good osteoconductivity by more BMSC adhesion around the holes. The confocal microscopy results showed that cells in porous Mg-based alloy had better cytoskeletal morphology and were larger in number than in titanium., Conclusions: These results indicated that this porous Mg-based alloy fabricated by infiltration casting shows great mechanical properties and biocompatibilities, and it has potential as an ideal bone tissue engineering scaffold material for bone regeneration., (© 2018 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objectives: The present study aimed to investigate the overall effect of quercetin on mouse bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation in vitro ., Materials and Methods: BMSCs were treated with different concentrations of quercetin for 6 days. The effects of quercetin on cell proliferation were assessed at predetermined times using Cell Counting Kit-8 (CCK-8) assay. The cells were then treated with quercetin, estrogen, or an estrogen receptor (ER) antagonist (which was also administered in the presence of quercetin or estrogen) for 7 or 21 days. The effects of quercetin on BMSC osteogenic differentiation were analyzed by an alkaline phosphatase (ALP) assay kit, Alizarin Red S staining (ARS), quantitative real-time PCR (qPCR), and western blotting., Results: The CCK-8 and ALP assays and ARS staining showed that quercetin significantly enhanced BMSC proliferation, ALP activity, and extracellular matrix production and mineralization, respectively. The qPCR results indicated that quercetin promoted osterix (OSX) , runt-related transcription factor 2 (RUNX2) , and osteopontin (OPN) transcription in the presence of osteoinduction medium, and the western blotting results indicated that quercetin enhanced bone morphogenetic protein 2 (BMP2), Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Treatment with the ER inhibitor ICI182780 blocked the effects of quercetin., Conclusions: Our data demonstrated that quercetin promotes BMSC proliferation and osteogenic differentiation. Quercetin enhances BMP signaling pathway activation and upregulates the expression of downstream genes, such as OSX , RUNX2 , and OPN , via the ER.

Background: Hidden blood loss (HBL) often occurs in the prosthetic replacement for joint, but the mechanism is still not clear., Materials and Methods: This study tried to establish an animal model of HBL by injecting arachidonic acid (AA) into the Sprague-Dawley rats. Different concentrations of AA were injected into the tail veins of the rats, and blood samples were collected before and after administration at 24, 48, and 72 h. A complete blood count was obtained by to find the hemoglobin (Hb) and red blood cell (RBC) count changes. The glutathione peroxidase (GSH-PX) and total superoxide dismutase (T-SOD) activities and hydrogen peroxide (H 2 O 2 ) levels were detected. The morphological changes of erythrocyte were observed under a polarizing microscope. The absorbance values of the blood samples were tested to determine the presence of ferryl Hb., Results: HBL occurred in the experimental groups when the concentration of AA reached 10 mmol/L; Hb and RBC values decreased sharply at 24- and 48-h postinjection. This was followed by reduced activities of GSH-PX and T-SOD and decreased levels of H 2 O 2 . Moreover, the pathologic changes of red cell morphology mainly presented as pleomorphic RBC morphology, including cell rupture. The absorbance values of the blood samples were in accordance with ferryl Hb features. RBC and Hb values were relatively stable at 72 h. The GSH-PX and T-SOD activities and H 2 O 2 levels gradually increased up to a balanced state., Conclusions: The study concluded that high concentrations of AA can induce oxidative stress reactions in the body, causing acute injury of RBCs, which is closely related to HBL., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The mechanism of human β-defensin 3 (HBD-3) in methicillin-resistant Staphylococcus aureus (MRSA-induced infection of implant drug-resistant bacteria biofilm in the mouse tibial bone marrow was studied. Healthy adult male Sprague-Dawley rats with average weight of 230 g were selected to construct the infection model of MRSA-induced implant drug-resistant bacteria biofilm in the mouse left tibial bone marrow. The drugs were intraperitoneally injected after 24 h medullary cavity infection, and the experimental groups included the model group, HBD-3 group, and vancomycin group (20 rats in each group). The model group was injected with 10 ml saline, HBD-3 group was injected with 10 ml of 8 µg/ml (1 MIC) and vancomycin group was injected with 10 ml of 0.5 µg/ml (1 MIC), five animals in each group were sacrificed on the 1, 7, 14 and 21 days, respectively. Observation was carried out on whether there was swelling and purulent secretion on the local wound; 1 ml venous sinus blood of eye socket was collected for blood routine examination and blood culture, and the laser scanning confocal microscopy was used to observe the morphology of the biofilm on the implant surface and the number of viable bacteria. Immunohistochemical staining was adopted to test the expression of nuclear factor-κB (NF-κB) and toll-like receptor 4 (TLR-4), and ELISA method was used to test interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), IL-1α and interferon-γ (INF-γ)-inducible protein-10 (IP-10) expression levels. There was no death due to infection in the HBD-3 group or vancomycin group, 1 case with significant wound swelling was found, respectively, in each group, but there was no purulent secretion. The percentage of the total white blood cells and neutrophil granulocytes as well as the biofilm morphology and the number of viable bacteria in the model group was gradually increased with time, while those in the HBD-3 group and vancomycin group were decreased with time. The comparative difference among groups was statistically significant (P<0.05); those in the HBD-3 group and vancomycin group at each time-point was decreased significantly compared with the model group, and the difference among groups was statistically significant (P<0.05), but in terms of the comparison between the HBD-3 group and vancomycin group, the difference was not significantly different (P>0.05). The NF-κB and TLR-4 expressions in the model group and vancomycin group were not significantly changed at each time-point, those in the HBD-3 group began to increase on the 1st day, and reached the peak on the 7th day and began to decline on the 14th day, and the comparative difference at each time-point was statistically significant (P<0.05); those in the HBD-3 group were significantly higher than the model group and vancomycin group at each time-point and the difference was statistically significant (P<0.05). The IL-10, TNF-α, IL-1α, and IP-10 expressions in the model group at each time were significantly higher than the other two groups and the difference was statistically significant (P<0.05); in terms of the comparison between the HBD-3 group and vancomycin group, the difference was not statistically significant (P>0.05). In conclusion, β-defensin 3 can inhibit the bacterial growth by regulating inflammation and immune responses in the MRSA-induced implant drug-resistant bacteria biofilm infection in the mouse tibial bone marrow.

The aim of the study was to investigate the mechanisms of human β-defensin 3 (HBD-3) regulation of the immune response and the lipopolysaccharide/Toll-like receptor-4 (LPS/TLR4)-mediated signaling pathway. A TLR4 extracellular gene fragment was cloned into the pET32a plasmid to determine its expression in Escherichia coli (E. coli) and purification. A dialysis labeling method was used to stain HBD-3 with fluorescein isothiocyanate (FITC). FITC-HBD-3 was used to induce the differentiation of human peripheral blood mononuclear cells (MNC) into immature dendritic cells (imDC) in vitro . Binding reactions were established using FITC-HBD-3 and sTLR4 into cell suspensions. Flow cytometry (FCM) was used to analyze the results. Western blot analysis confirmed the identity of nuclear factor-κB (NF-κB) and was used to quantify its nuclear translocation. The results showed that, HBD-3 bound to imDC in a Ca 2+ -dependent manner, and sTLR4 and LPS competitively inhibited the binding. HBD-3 competitively blocked the binding of LPS and imDC by binding to imDC. HBD-3 significantly decreased the translocation of LPS-induced NF-κB into the nucleus. In conclusion, HBD-3 can competitively inhibit the binding of LPS and imDC through its binding to TLR4 molecules, which are expressed in imDC, thereby preventing LPS from inducing the maturity of the imDCs.

Autophagy plays an important role in spinal cord ischemia reperfusion (I/R) injury, but its neuroprotective or neurodegenerative role remains controversial. The extent and persistence of autophagy activation may be the critical factor to explain the opposing effects. In this study, the different roles and action mechanisms of autophagy in the early and later stages after I/R injury were investigated in rats. Thespinal cord I/R injury was induced by 14-min occlusion of the aortic arch, after which rats were treated with autophagic inhibitor (3-methyladenine, 3-MA) or agonist (rapamycin) immediately or 48h following the injury. Autophagy markers, microtubule-associated protein light chain 3-II (LC3-II) and Beclin 1 increased and peaked at the early stage (8h) and the later stage (72h) after spinal cord I/R injury. Beclin 1 was mostly expressed in neurons, but was also expressed to an extent in astrocytes, microglia and vascular endothelial cells. 8h after injury, rats treated with 3-MA showed a decrease in the hind-limb Basso-Beattie-Bresnahan (BBB) motor function scores, surviving motor neurons, and B-cell lymphoma-2 (Bcl-2) expression, and increase in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells, Bcl-2-associated X protein (Bax), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) expression, and activation of microglia, while those treated with rapamycin showed opposing effects. However, 72h after injury, rats treated with 3-MA improved the BBB scores, and the surviving motor neurons, and reduced the autophagic cell death, while those treated with rapamycin had adverse effects. These findings provide the first evidence that early activated autophagy alleviates spinal cord I/R injury via inhibiting apoptosis and inflammation; however later excessively elevated autophagy aggravates I/R injury through inducing autophagic cell death., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Genetic factors have been shown to be of great importance for the pathogenesis of bone diseases, such as fracture, osteoporosis (OP), and osteoarthritis (OA). However, published studies on the correlations of transforming growth factor-β1 (TGF-β1) gene polymorphisms with bone diseases have been hampered by small sample sizes or inconclusive findings. We hence aimed at examining the relationships between a single nucleotide polymorphism in the TGF-β1 gene (rs1982073 C>T) with bone fracture, OP, and OA risks in this meta-analysis. A systematic electronic search of literature was conducted to identify all published studies in English or Chinese on the association between the TGF-β1 gene and fracture, OP, or OA risks. Data were abstracted independently by two reviewers. To investigate the strength of this relationship, crude odds ratios with 95 % confidence intervals were used. An updated meta-analysis based on nine independent case-control studies were chosen (patients with fracture, OP, or OA = 1569; healthy controls = 1638). Results identified a higher frequency of rs1982073 C>T in patients with fracture, OP, or OA than in healthy controls. Ethnicity and genotyping method-stratified analysis under both models implied that the rs1982073 C>T polymorphism was positively correlated with the risk of fracture, OP, and OA among Asians under detection via the non-PCR-RFLP method. Disease-stratified results yielded that rs1982073 C>T may increase the risk of fracture, OP, and OA under the allele model, but was only significantly related to OP under the dominant model. According to the sample size-stratified analysis, subjects with the rs1982073 C>T polymorphism in the allele model were more likely to develop the three bone diseases in both the small and large sample size groups, and only in the large sample size under the dominant model. Our findings show that TGF-β1 rs1982073 C>T has a modest effect in increasing susceptibility to bone fracture, OP, and OA.

Objective: To study the correlation between arachidonic acid (AA) and acute red blood cells damage in rats, and to build a model with hidden blood loss in vivo, and to explore the pathological mechenism of hidden blood loss., Methods: A total of 50 male adult Sprague-Dawley rats weighing (200 ± 20) g were randomly divided into five groups (n = 10): control group and four experimental groups. The rats in the experimental groups were given 0.5 ml different concentrations of AA dilu- ents, 5, 10, 20, 40 mmol/L respectively. The blood samples were collected from orbital venous at the beginning and 24, 48, 72 hours after administration. Then the changes of hemoglobin (Hb) ,red blood cell count (RBC), glutathione peroxidase (GSH- PX) activity, total superoxide dismutase (T-SOD) activity and hydrogen peroxide (H202) in the blood samples were tested., Results: Significant hidden blood loss occurred when the concentration was 10 mmol/L in the experimental group, with the RBC and Hb sharply reduced in blood samples. The Hb and RBC were reduced in all the experimental groups and control group at 24 hours after administration, while in the experimental groups they changed more obviously. The GSH-PX activity, T-SOD activity and H₂O₂were also significantly reduced in all groups, and the changes showed significant differences. The Hb and RBC were relatively stable in the control group and the experimental groups at 48 hours after administration; while GSH-PX activity, T-SOD activity and H₂O₂were all significantly decreased, and the changes in the experimental groups were more notable., Conclusion: Elevated levels of AA in the blood causes oxidative stress in the red blood cells, leading to the damage of red blood cells and hemoglobin, which is responsible for hidden blood loss.

Objective: To systematically evaluate the efficacy and safety of preoperative administration of cyclooxygenase-2 (COX-2) inhibitor on pain occurring with total knee arthroplasty (TKA)., Methods: We electronically searched PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang data from inception to March 15, 2014 and manual searched journal of library collection to identify randomized controlled trials (RCTs) about preoperative administration of COX-2 inhibitor on pain occurring with TKA. The methodological quality of the included RCTs was assessed and the data were extracted according to the Cochrane Handbook 5.1.0. Meta-analysis was performed by using RevMan 5.2 software., Results: A total of 6 RCTs involving 228 patients were included. The results of meta-analyses showed that: (1) Efficacy: The visual analog scale (VAS) of post-operation at 12-hour (WMD = -0.60, 95% CI -0.83 to -0.37, P < 0.000 01) and 24-hour (WMD = -0.74, 95% CI -1.29 to - 0.19, P = 0.008) was decreased when COX-2 inhibitor was used before operation. And compared with control group, experimental group decreased the modified numerical pain rating scale (MNPRS) at 24-hour (WMD = -0.50, 95% CI -0.70 to -0.30, P < 0.000 01), 48-hour (WMD = -0.55,95% CI -0.65 to -0.45,P < 0.000 01) under quiescent conditions, and the same result at 24-hour (WMD = -0.82, 95% CI -1.26 to -0.38, P <0.000 01), 48-hour (WMD = -0.71, 95% CI -0.82 to -0.60, P < 0.000 01) under active conditions. The morphine consumption postoperatively were fewer in experimental group at the first day (WMD = - 1.35, 95% CI -1.92 to -0.79, P < 0.000 01) and the second day (WMD = -1.60, 95% CI -2.68 to -0.52, P = 0.004). (2) Safety: COX-2 inhibitor could lessen the incidence of postoperative pruritus (RR = 0.35, 95% CI 0.15 to 0.84, P = 0.02), but not statistically decrease of nausea and vomiting (RR = 0.83, 95% CI 0.54 to 1.28, P = 0.40) and exhaustion (RR = 0.63, 95% CI 0.05 to 7.67, P = 0.72)., Conclusion: The current evidence indicated that preoperative administration of COX-2inhibitor can effectively improve the effect of postoperative analgesia, reduce the consumption of morphine and lessen the incidence of pruritus. Due to the limited quantity of the included studies and the evidence with limited strength,further high-quality RCTs are needed to verify the aforementioned conclusion.

Hidden blood loss typically occurs following total hip arthroplasty (THA) and total knee arthroplasty (TKA) and is thought to be related to free fatty acid (FFA). To study the effect of linoleic acid on red blood cells and to examine the pathogenesis of hidden blood loss in vivo, we generated an animal model by injecting linoleic acid into the tail veins of rats. We collected blood samples and determined red blood cell count (RBC) and levels of hemoglobin (Hb), as well as the oxidation and reducing agents in the blood, including glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), hydrogen peroxide (H2O2), and ferryl hemoglobin (Fe4+=O2-), which is generated by the oxidation of Hb. Hidden blood loss occurred when linoleic acid was administered at a concentration of 60 mmol/L; RBC and Hb levels were significantly reduced by 24 h post-injection. This was followed by erythrocyte deformation, reduced activity of GSH-PX and T-SOD, and decreased levels of H2O2. This was accompanied by an increase in ferryl species, which likely contributes to oxidative stress in vivo. Our findings suggest that linoleic acid enhances acute red blood cell injury. Hb and RBC began to increase by 72 h, potentially resulting from linoleic acid metabolism. Thus, elevated levels of linoleic acid in the blood cause acute oxidative damage to red blood cells, eventually leading to partial acute anemia. These findings highlight the pathophysiology underlying hidden blood loss.

Total hip arthroplasty (THA) is a vital therapeutic tool for hip terminal disease. Frequently, hidden blood loss exists in the postoperation, which seriously affect the postoperative rehabilitation of patients. It is urgent need to solve the problem that how to fundamentally prevent and reduce hidden blood loss after THA. Although THA has its own operational reason in blood loss, and also relates to a variety of risk factors, the mechanism of hidden blood loss is not clear. Tranexamic acid has a significant role in preventing perioperative blood loss, and the correlation of hidden blood loss and fibrinolytic mechanism would be confirm necessarily in the future,which will produce positive significance in completing the mechanism of hidden blood loss.

Objective: To detect the clinical value of the ECT bone scan in evaluating of the situation of infection control after hip knee arthroplasty., Methods: The clinical data were retrospectively analyzed in 62 patients, including 34 males and 28 females with an average age of 68.8 years old ranging from 65 to 74 years. The results of ECT bone scan, erythrocyte sedimentation rate, C-reactive protein were used to assess periprosthetic infection. The patients with positive ECT and ESR on CRP were considered to have periprosthetic infection; however, the patients with two or more negative, indexes were considered to have no infection., Results: The sensitivity, specificity, accurate rate of ECT were 75.0%, 88.9%, 87.1% respectively; ESR 50.0%, 72.2%, 69.4%; CRP 62.5%, 81.4%, 79.0%. The combination of the three methods were 87.5%, 96.3% and 95.2%,, Conclusion: Compared with ESR and CRP, ECT is a more effective way in the diagnosis of periprosthetic infection, which has great value and is worth popularizing.

Total knee arthroplasty (TKA) has been successfully applied for the treatment of the knee pathology at the end stage such as osteoarthritis and rheumatoid arthritis. Although TKA has became a very mature technology, some patients still suffer from the persistent pain after surgery. The cause of this pain have been recognized as the operation or technical error in most cases, and it usually requires a surgical intervention. Only when the cause of pain is judged accurately, can the operation and other factors be estimated correctly, determining the appropriate treatment methods. In the article, the causes of the post-operative pain after TKA are reviewed, which may be helpful to study the causes of the pain, and to decrease the occurrence incidence of pain.

Cancer treatment-related bone loss has become growing problematic, especially in breast and prostate cancer treated with hormone/endocrine therapy, chemotherapy and radiotherapy. However, bone loss caused by targeted therapy in cancer patients is largely unknown yet. In present study, a kinase inhibitors screen was applied for MC3T3-E1, a murine osteoprogenitor cell line, and seven kinase inhibitors (GSK1838705A, PF-04691502, Dasatinib, Masitinib, GDC-0941, XL880 and Everolimus) were found to suppress the cell viability with dose- and time-dependent manner. The most interesting is that many kinase inhibitors (such as lapatinib, erlotinib and sunitinib) can promote MC3T3-E1 cell proliferation at 0.01 μM. 4 out of 7 inhibitors were selected to perform the functional study and found that they lead to cell cycle dysregulation, treatments of PF-04691502 (AKT inhibitor), Dasatinib (Src inhibitor) and Everolimus (mTOR inhibitor) lead to G1 arrest of MC3T3-E1 cells via downregulation of cyclin D1 and p-AKT, whereas XL880 (MET and VEGFR inhibitor) treatment results in increase of sub-G1 and G2/M phase by upregulation of p53 protein. Our work provides important indications for the comprehensive care of cancer patients treated with some targeted drugs.

Bidirectional Eph-Ephrin signaling as a focal point of research in cell-cell communications is critical for generation of nerves and vesssels as well as invation and metastasis of tumor cells. The roles for Ephrin-Eph bidirectional signaling in bone remodeling were important. EphrinB2 is expressed on osteoblasts and EphB4 is expressed on osteoclasts. Forward signaling through the EphB4 receptor into mesenchymal precursors promotes osteoblast differentiation, while reverse signaling through the EphrinB2 ligand into osteoclast suppresses differentiation. Signaling between the ligand EphrinB2 and the receptors EphB4 explains bidirectional signaling between osteoblasts and osteoclasts,bone absorption and remodeling, which may lay a theoretical foundation for identifying drug targeting and preventing and treating bone loss.

Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan's Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-α (TNF-α) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-α mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-α expression.

Objective: To investigate the principle and methods of preoperative and postoperative rehabilitation for simultaneous bilateral total knee arthroplasty., Methods: From January 2005 to June 2008, 72 patients (144 knees) were reviewed in the study, including 33 males and 39 females, ranging in age from 46 to 78 years, with an average age of 69 years. There were 54 patients with osteoarthritis, 17 patients with RA, and 1 patient with traumatic osteoarthritis, including 10 cases (15 knees) of fixed varus deformity more than 30 degree and 6 cases (8 knees) of fixed vagus deformity more than 15 degree. Rehabilitation protocol was made for preoperative, early postoperative and late postoperative stages. Patients were encouraged to initiate the exercises at the early postoperative stage on the premise of multimodal analgesia. Knee function and pain were evaluated using WOMAC and VAS pain scores. Lower limb embolism was determined by ultrasonic scan and pulmonary embolism was diagnosed by clinical manifestation and D-dimer level., Results: Sixty-nine patiets (138 knees) were followed up at 2 d preoperatively and the second day, 1, 2, 8 and 24 weeks postoperatively. The average postoperative WOMAC and VAS score were significantly lower than preoperative levels,while the postoperative knee ROM and 6 min walking distance were evidently higher than the preoperative ones, respectively. One hundred and twenty-eight knees achieved full extension and flexion more than 90 degree at 2 weeks postoperatively, and 135 knees reached 110 degree in flexion. Unilateral lower limb embolism was found in 2 cases (2 knees) and bilateral ones were found in 1 case (2 knees). No pulmonary embolism was confirmed., Conclusion: Rehabilitation protocols should be made for preoperative, early postoperative and late postoperative stages of simultaneous bilateral knee arthroplasty. Patients should be encouraged to exercise at the early postoperative stage on the premise of multimodal analgesia, in order to improve knee function and reduce edema.

Objective: To explore the prognostic significance of hidden blood loss in total hip arthroplasty., Methods: From May 2008 to July 2009, Harris hip score was used to evaluate the functions of 71 patients undergoing single side total hip arthroplasty (including 47 males and 24 females with a mean age of 68.3 years, ranged from 48 to 75 years). The blood loss in the operation was analyzed to study the correlation between hidden blood loss and the functional rehabilitation., Results: All 71 patients undergoing THA were involved in the result analysis. The mean total blood loss was 1473 ml and the hidden blood loss was 545 ml (37%). Hidden blood loss significantly correlated with functional rehabilitation (P = 0.001), but there were no correlations between functional rehabilitation and age, gender, operative limb of patients (P = 0.067, 0.527, 0.926, 0.072)., Conclusion: Hidden blood loss maybe a useful prognostic information contributing to the functional rehabilitation of total hip arthroplasty.

Objective: To investigate the curative effect of treating infected nonunion with debridement and granulated cancellous bone autografting in a one-stage procedure., Methods: Between 1999 and 2005, 38 cases of infected nonunion were treated with immediate granulated cancellous bone autografting after debridement., Results: At a mean follow-up of 44 months (range: 12 to 93), 33/38 (86.8%) had an excellent outcome, 5 (13.2%) developed infectious recurrent and/or persistent nonunion (1 case with infectious recurrence and persistent nonunion). Two patients suffered refracture after removing external fixator., Conclusion: The success rate of treating infected nonunion with debridement and granulated cancellous bone autografting in one-stage is high.

Objective: To analyze the complications of bipolar hemiarthroplasty for the treatment of intertrochanteric fractures., Methods: From Jan. 2004 to Dec. 2007, 62 patients over 80 years old with unstable interthochanteric fracture were treated with bipolar hemiarthroplasty, included 34 males and 28 females with an average age of 86.3 years ranging from 81 to 97 years. According to the Evans classification, there were 29 cases of Evans III, 26 of Evans IV and 7 of Evans V. The systemic and operation related complications were investigated., Results: Among all the cases, 59 were followed up in outpatient department for 24 to 70 months (33 months on average). Systemic complications were found in 19 cases with no death during preoperative period and 5 deaths after leaving hospital. Operation related complications were found in 9 cases, included 3 cases of thigh pain, 1 iatrogenic fracture of proximal femur, 2 hip dislocations, 2 delayed union of fractures and 1 superficial infection. There were no aseptic loosening, peri-prosthetic infections,ectopic ossification or injuries of nerves and vessels., Conclusion: Bipolar hemiarthroplasty is indicated for patients over 80 years old with intertrochanteric fracture, thus the organic or systemic malfunctions should be corrected during perioperative period. Meanwhile, retaining of lesser trochanter and reconstruction of calcar femorale are important for improving periprosthetic biomechanics and reducing local complications.

Objective: To measure the concentration of osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (sRANKL) in peripheral blood among normal healthy people and investigate the relationship pf the concentration with age and sex., Methods: The peripheral blood samples of 220 normal healthy people (included 108 males and 112 females, aged from 35 to 70) were collected in the morning. The OPG and sRANKL concentration of blood serum were measured by ELISA., Results: The concentrations in female peripheral blood were: OPG 21.95 to 315.47 pg/ml, sRANKL 10.25 to 370.20 pmol/L; while in male were: OPG 14.78 to 192.55 pg/ml, sRANKL 9.22 to 300.32 pmol/L. There was positive correlation between the OPG concentration and age in the females older than 46 years. And for female older than 57, the sRANKL concentration of peripheral blood increases obviously., Conclusion: Age and sex are the elements that affect the OPG and sRANKL concentration in peripheral blood. For female older than 46, the OPG concentration of peripheral blood increases with age, while the sRANKL concentration of peripheral blood increases for females older than 57.

Objective: To avoid disadvantages of two-stage cancellus bone autograft, we investigated the feasibility of one-stage allograft for reconstructing the bone defect resulting from debridement of chronic osteomyelitis in limbs., Methods: Between Feb. 1999 and Apr. 2004, 35 cases of chronic osteomyelitis (8 cases of nonunion) underwent one-stage allograft after debridement in our hospital., Results: Thirty-five cases were followed up for an average period of 28 months (range, 13 to 55 months), in which 32 cases (91.43%) were found no infection, and 3 cases (8.57%) were confirmed recurrence of infection. Four out of 8 cases of bone nonunion healed in 9.5 months on average (range, 3 to 12 months), and another case also acquired union after redebridement and autograft of ilium due to infection recurrence 35 days after surgery. Renonunion occurred in 3 cases, 2 out of whom healed after secondary operation with autograft. One case of renonunion and 2 cases of infection recurrence refused further treatment., Conclusions: A high rate of infection arrest can be attained when one-stage allograft is used to reconstruct the bone defect of chronic osteomyelitis after debridement in limbs. Therefore, chronic osteomyelitis should not be regarded as a contraindication to one-stage allogeneic bone grafting. Renonuion, however, achieves a relatively high rate, especially in cases of segmental bone defect.

Study Design: To develop a high-accuracy, easy-manipulated, and low-cost cervical pedicle three-dimensional locator for guiding cervical pedicle screw placement., Objectives: To improve the safety of cervical pedicle screw insertion, simplify its manipulation, and offer safety guarantees in clinical application., Summary of Background Data: Because of the complicacy of the anatomic structure of cervical pedicle, clinical application of cervical pedicle screw remained hard to popularize. And recent advances on cervical pedicle location did not simplify the manipulation of procedure significantly. Without aid of locator, distance and angle errors were difficult to control. So far, the only instrument for the location of pedicle "computer-assisted image-guided surgical system" is too expensive for clinical use. Furthermore, it has not yet been documented on location instrument for insertion of cervical pedicle screws., Methods: The high-accuracy three-dimensional locator, made of stainless steel was designed to aid cervical pedicle nail placement. The cadavers were inserted nails under guidance of the locator that has been input the corresponding parameters collected from CT images. Results were evaluated by CT scans., Results: A total of 90 nails were inserted into cervical pedicles, 90% of which were found right in the pedicles; 10% had pedicle cortex breaches. Parallel offset error of the locator in cross-sectional and lateral CT image that was 0.56 +/- 0.70 and 1.04 +/- 0.99; angular offset error was 1.69 +/- 2.41 and 6.54 +/- 7.08., Conclusion: Three-dimensional locator of cervical pedicle and its localization technique achieved good results for individuated screws insertion into cervical pedicles, having such advantages as easy manipulation, high accuracy, and low cost. The system presented safety guarantee to the application and advanced the prevalence of pedicle techniques. Its principium and design were demonstrated feasible.