Preparation and efficacy of antibacterial methacrylate monomer-based polymethyl methacrylate bone cement containing N-halamine compounds.

Introduction: Our objective in this study was to prepare a novel type of polymethyl methacrylate (PMMA) bone cement, analyze its material properties, and evaluate its safety and antibacterial efficacy. Methods: A halamine compound methacrylate antibacterial PMMA bone cement containing an N-Cl bond structure was formulated, and its material characterization was determined with Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The antibacterial properties of the material were studied using contact bacteriostasis and releasing-type bacteriostasis experiments. Finally, in vitro and in vivo biocompatibility experiments were performed to analyze the toxic effects of the material on mice and embryonic osteoblast precursor cells (MC3T3-E1). Results: Incorporation of the antibacterial methacrylate monomer with the N-halamine compound in the new antibacterial PMMA bone cement significantly increased its contact and releasing-type bacteriostatic performance against Staphylococcus aureus. Notably, at 20% and 25% additions of N-halamine compound, the contact and releasing-type bacteriostasis rates of bone cement samples reached 100% (p < 0.001). Furthermore, the new antibacterial bone cement containing 5%, 10%, and 15% N-halamine compounds showed good biocompatibility in vitro and in vivo. Conclusion: In this study, we found that the novel antibacterial PMMA bone cement with N-halamine compound methacrylate demonstrated good contact and releasing-type bacteriostatic properties against S. aureus. In particular, bone cement containing a 15% N-halamine monomer exhibited strong antibacterial properties and good in vitro and in vivo biocompatibility.

Injectable isoniazid-loaded bone cement based on hydrazone bonds achieving long-term release and decent mechanical properties.

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

Investigating the in vitro antibacterial efficacy of composite bone cement incorporating natural product-based monomers and gentamicin.

OBJECTIVE: The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). METHODS: Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. RESULTS: The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). CONCLUSION: In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.

CCL2 Knockdown Attenuates Inflammatory Response After Spinal Cord Injury Through the PI3K/Akt Signaling Pathway: Bioinformatics Analysis and Experimental Validation.

Spinal cord injury (SCI) is a common clinical problem in orthopedics with a lack of effective treatments and drug targets. In the present study, we performed bioinformatic analysis of SCI datasets GSE464 and GSE45006 in the Gene Expression Omnibus (GEO) public database and experimentally validated CCL2 expression in an animal model of SCI. This was followed by stimulation of PC-12 cells using hydrogen peroxide to construct a cellular model of SCI. CCL2 expression was knocked down using small interfering RNA (si-CCL2), and PI3K signaling pathway inhibitors and activators were used to validate and observe the changes in downstream inflammation. Through data mining, we found that the inflammatory chemokine CCL2 and PI3K/Akt signaling pathways after SCI expression were significantly increased, and after peroxide stimulation of PC-12 cells with CCL2 knockdown, their downstream cellular inflammatory factor levels were decreased. The PI3K/Akt signaling pathway was blocked by PI3K inhibitors, and the downstream inflammatory response was suppressed. In contrast, when PI3K activators were used, the inflammatory response was enhanced, indicating that the CCL2-PI3K/Akt signaling pathway plays a key role in the regulation of the inflammatory response. This study revealed that the inflammatory chemokine CCL2 can regulate the inflammatory response of PC-12 cells through the PI3K/Akt signaling pathway, and blocking the expression of the inflammatory chemokine CCL2 may be a promising strategy for the treatment of secondary injury after SCI.

Comparison of antibacterial activity and biocompatibility of non-leaching nitrofuran bone cement loaded with vancomycin, gentamicin, and tigecycline.

BACKGROUND: Non-leaching antibacterial bone cement can generate long-term antibacterial activity, it cannot treat serious infections that have occurred like antibiotic-loaded bone cement. Currently, the antibacterial activity and biocompatibility of non-leaching cement when loaded with antibiotics have yet to be determined. METHODS: Non-leaching antibacterial nitrofuran bone cement (NFBC) specimens were prepared with low-dose and high-dose antibiotics. The antibacterial activity and biocompatibility of NFBC loaded with vancomycin, gentamicin, and tigecycline were compared. The agar diffusion method was employed to observe the inhibition zone of the samples against two bacterial strains from day one to day seven. The CCK-8 assay and acute liver and kidney toxicity test were conducted to assess the effects of the samples on mouse embryo osteoblast precursor cells and C57 mice, respectively. RESULTS: Gentamicin-loaded cement exhibited the most potent antibacterial activity, effectively inhibiting both bacterial strains at a low dose. Tigecycline-loaded cement demonstrated superior biocompatibility, showing no acute liver and kidney toxicity in mice and minimal cytotoxicity to osteoblasts. CONCLUSIONS: NFBC loaded with gentamicin, vancomycin, and tigecycline not only maintains sustained antibacterial activity but also exhibits excellent biocompatibility.

Identification of the CCL2 PI3K/Akt axis involved in autophagy and apoptosis after spinal cord injury.

Spinal cord injury (SCI) is a devastating neurological disease with no cure that usually results in irreversible loss of sensory and voluntary motor functions below the injury site. We conducted an in-depth bioinformatics analysis combining the gene expression omnibus spinal cord injury database and the autophagy database and found that the expression of the autophagy gene CCL2 was significantly upregulated and the PI3K/Akt/mTOR signaling pathway was activated after SCI. The results of the bioinformatics analysis were verified by constructing animal and cellular models of SCI. We then used small interfering RNA to inhibit the expression of CCL2 and PI3K to inhibit and activate the PI3K/Akt/mTOR signaling pathway; western blot, immunofluorescence, monodansylcadaverine, and cell flow techniques were used to detect the expression of key proteins involved in downstream autophagy and apoptosis. We found that when PI3K inhibitors were activated, apoptosis decreased, the levels of autophagy-positive proteins LC3-I/LC3-II and Bcl-1 increased, the levels of autophagy-negative protein P62 decreased, the levels of pro-apoptotic proteins Bax and caspase-3 decreased, the levels of the apoptosis-inhibiting protein Bcl-2 increased. In contrast, when a PI3K activator was used, autophagy was inhibited, and apoptosis was increased. This study revealed the effect of CCL2 on autophagy and apoptosis after SCI through the PI3K/Akt/mTOR signaling pathway. By blocking the expression of the autophagy-related gene CCL2, the autophagic protective response can be activated, and apoptosis can be inhibited, which may be a promising strategy for the treatment of SCI.

Can a Nomogram Predict Survival After Treatment for an Ankylosing Spondylitis Cervical Fracture in a Patient With Neurologic Impairment? A National, Multicenter Study.

BACKGROUND: Ankylosing spondylitis-related cervical spine fracture with neurologic impairment (ASCF-NI) is a rare but often lethal injury. Factors independently associated with survival after treatment remain poorly defined, and identifying patients who are likely to survive the injury remains challenging. QUESTIONS/PURPOSES: (1) What factors are independently associated with survival after treatment among patients with ASCF-NI? (2) Can a nomogram be developed that is sufficiently simple for clinicians to use that can identify patients who are the most likely to survive after injury? METHODS: This retrospective study was conducted based on a multi-institutional group of patients admitted and treated at one of 29 tertiary hospitals in China between March 1, 2003, and July 31, 2019. A total of 363 patients with a mean age of 53 ± 12 years were eventually included, 343 of whom were male. According to the National Household Registration Management System, 17% (61 of 363) died within 5 years of injury. Patients were treated using nonsurgical treatment or surgery, including procedures using the anterior approach, posterior approach, or combined anterior and posterior approaches. Indications for surgery included three-column injury, unstable fracture displacement, neurologic impairment or continuous progress, and intervertebral disc incarceration. By contrast, patients generally received nonsurgical treatment when they had a relatively stable fracture or medical conditions that did not tolerate surgery. Demographic, clinical, and treatment data were collected. The primary study goal was to identify which factors are independently associated with death within 5 years of injury, and the secondary goal was the development of a clinically applicable nomogram. We developed a multivariable Cox hazards regression model, and independent risk factors were defined by backward stepwise selection with the Akaike information criterion. We used these factors to create a nomogram using a multivariate Cox proportional hazards regression analysis. RESULTS: After controlling for potentially confounding variables, we found the following factors were independently associated with a lower likelihood of survival after injury: lower fracture site, more-severe peri-injury complications, poorer American Spinal Injury Association (ASIA) Impairment Scale, and treatment methods. We found that a C5 to C7 or T1 fracture (ref: C1 to C4 and 5; hazard ratio 1.7 [95% confidence interval 0.9 to 3.5]; p = 0.12), moderate peri-injury complications (ref: absence of or mild complications; HR 6.0 [95% CI 2.3 to 16.0]; p < 0.001), severe peri-injury complications (ref: absence of or mild complications; HR 30.0 [95% CI 11.5 to 78.3]; p < 0.001), ASIA Grade A (ref: ASIA Grade D; HR 2.8 [95% CI 1.1 to 7.0]; p = 0.03), anterior approach (ref: nonsurgical treatment; HR 0.5 [95% CI 0.2 to 1.0]; p = 0.04), posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.8]; p = 0.006), and combined anterior and posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.9]; p = 0.02) were associated with survival. Based on these factors, a nomogram was developed to predict the survival of patients with ASCF-NI after treatment. Tests revealed that the developed nomogram had good performance (C statistic of 0.91). CONCLUSION: The nomogram developed in this study will allow us to classify patients with different mortality risk levels into groups. This, coupled with the factors we identified, was independently associated with survival, and can be used to guide more appropriate treatment and care strategies for patients with ASCF-NI. LEVEL OF EVIDENCE: Level III, therapeutic study.

Improvement of sleep quality in isolated metastatic patients with spinal cord compression after surgery.

BACKGROUND: This study aimed to assess changes in quality of sleep (QoS) in isolated metastatic patients with spinal cord compression following two different surgical treatments and identify potential contributing factors associated with QoS improvement. METHODS: We reviewed 49 patients with isolated spinal metastasis at our spinal tumor center between December 2017 and May 2021. Total en bloc spondylectomy (TES) and palliative surgery with postoperative stereotactic radiosurgery (PSRS) were performed on 26 and 23 patients, respectively. We employed univariate and multivariate analyses to identify the potential prognostic factors affecting QoS. RESULTS: The total Pittsburgh Sleep Quality Index (PSQI) score improved significantly 6 months after surgery. Univariate analysis indicated that age, pain worsening at night, decrease in visual analog scale (VAS), increase in Eastern Cooperative Oncology Group performance score (ECOG-PS), artificial implant in focus, and decrease in epidural spinal cord compression (ESCC) scale values were potential contributing factors for QoS. Multivariate analysis indicated that the ESCC scale score decreased as an independent prognostic factor. CONCLUSIONS: Patients with spinal cord compression caused by the metastatic disease had significantly improved QoS after TES and PSRS treatment. Moreover, a decrease in ESCC scale value of > 1 was identified as a favorable contributing factor associated with PSQI improvement. In addition, TES and PSRS can prevent recurrence by achieving efficient local tumor control to improve indirect sleep. Accordingly, timely and effective surgical decompression and recurrence control are critical for improving sleep quality.

Efficacy and safety of erythropoietin in isolated spinal metastasis patients with total en bloc spondylectomy surgery: a case-control study.

OBJECTIVE: The purpose of our study is to identify the effect of short-term and high-dose use of erythropoietin (EPO) in spinal isolated metastatic patients with Total en bloc spondylectomy (TES) surgery by assessing hematological parameters, transfusion volume, postoperative complications, recurrence-free survival (RFS), and overall survival (OS). METHODS: From January 2015 and January 2022, 93 isolated spinal metastasis patients were selected and separated into 2 groups based on the treatment method used (EPO + TXA (Tranexamic acid) group, n = 47; and TXA group, n = 46). Indexes for evaluation included hemoglobin (Hb), hematocrit (Hct), red blood cells (RBC), RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, transfusion rate, and mean units transfused. RESULTS: The average follow-up duration was 38.13 months. There was no significant difference (P > 0.05) in RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, and transfusion rate between the two groups. However, patients in EPO + TXA group have significantly higher Hb, Hct, and RBC values than those in the TXA group on postoperative days 1, 2, 3, and 5. Moreover, the mean transfusion volume in EPO + TXA group was significantly lower than those in the TXA group (P = 0.011). CONCLUSIONS: Perioperative short-term and high-dose administration of EPO could improve the anemia-related hematological parameters and reduce the requirement for blood transfusion without increasing the risk of deep vein thrombosis and tumor progression in solitary spinal metastatic patients with TES surgery.

Analysis of risk factors for perioperative hidden blood loss in patients undergoing transforaminal lumbar interbody fusion.

OBJECTIVE: This study was performed to analyze the correlation between perioperative hidden blood loss (HBL) and the general condition of patients undergoing transforaminal lumbar interbody fusion (TLIF). METHODS: We retrospectively analyzed patients who underwent TLIF from July 2017 to July 2019 in our hospital. Sex, age, body mass index, underlying diseases, American Society of Anesthesiologists classification, coagulation function, preoperative and postoperative hemoglobin level and hematocrit, surgery time, fusion level, intraoperative blood loss, and drainage volume were recorded. Postoperative complications were also recorded. The amount of HBL was calculated, and its correlation with related variables was analyzed. RESULTS: The mean surgery time was 153.32 ± 54.86 minutes. The total perioperative blood loss was 789.22 ± 499.68 mL, including HBL of 315.69 ± 199.87 mL. Pearson correlation analysis showed statistically significant differences in HBL according to the body mass index, hypertension, fibrinogen, surgery time, and fusion level. Multiple linear regression analysis indicated that the surgery time and fusion level were independent risk factors for HBL. CONCLUSIONS: A certain amount of HBL occurs in TLIF surgery and cannot be ignored in daily clinical work. The operation time and surgery level are independent risk factors for HBL.

Bright Fluorescent Vacuolar Marker Lines Allow Vacuolar Tracing Across Multiple Tissues and Stress Conditions in Rice.

The vacuole is indispensable for cells to maintain their water potential and to respond to environmental changes. Nevertheless, investigations of vacuole morphology and its functions have been limited to Arabidopsis thaliana with few studies in the model crop rice (Oryza sativa). Here, we report the establishment of bright rice vacuole fluorescent reporter systems using OsTIP1;1, a tonoplast water channel protein, fused to either an enhanced green fluorescent protein or an mCherry red fluorescent protein. We used the corresponding transgenic rice lines to trace the vacuole morphology in roots, leaves, anthers, and pollen grains. Notably, we observed dynamic changes in vacuole morphologies in pollen and root epidermis that corresponded to their developmental states as well as vacuole shape alterations in response to abiotic stresses. Our results indicate that the application of our vacuole markers may aid in understanding rice vacuole function and structure across different tissues and environmental conditions in rice.

Liriodenine enhances radiosensitivity in esophageal cancer ECA-109 cells by inducing apoptosis and G2/M arrest.

At present, chemotherapy and radiotherapy represent the primary modalities of treatment for patients with unresectable esophageal squamous cell carcinoma (ESCC). However, the outcome of patients remains poor owing to radioresistance. The present study aimed to determine the radiosensitizing effect of liriodenine, an aporphine alkaloid derived from Enicosanthellum pulchrum, and investigating the underlying mechanisms in ESCC, using the esophageal cancer ECA-109 cell line. Cellular proliferation was evaluated using the Cell Counting kit-8 assay. Colony formation assay was performed to characterize the radiosensitive effects of liriodenine on ECA-109 cells, and flow cytometry was used to detect the percentage of cells undergoing apoptosis. An immunofluorescence assay was utilized to evaluate the DNA damage repair ability. Western blotting was used to assess the protein levels of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax). Liriodenine dose-dependently inhibited ECA-109 cell viability. The clonogenic survival assay demonstrated that liriodenine increased the radiosensitivity of ESCC cells, with a sensitization enhancement ratio of 1.11-1.69. The results of flow cytometry demonstrated that liriodenine induced apoptosis and G2/M arrest. The immunofluorescence assay revealed that liriodenine delays DNA damage repair. The upregulation of Bax and Caspase-3, and the suppression of Bcl-2 confirmed that apoptosis was occurring. Liriodenine radiosensitizes ECA-109 cells by inducing apoptosis and G2/M arrest. The findings of the present study indicated that liriodenine may represent an anticancer agent with promising potential for the treatment of ESCC.

The Efficacy of Immersive Virtual Reality Surgical Simulator Training for Pedicle Screw Placement: A Randomized Double-Blind Controlled Trial.

PURPOSE: To assess efficacy of immersive virtual reality (VR) surgical simulator training for pedicle screw placement (PSP) in surgical graduate students. METHODS: Sixteen inexperienced surgical graduate students were equally randomly assigned to an experimental group (VR group) and a control group (non-VR group). Students in the VR group performed PSP on the immersive VR surgical simulator, and students in the non-VR group were given a traditional introductory teaching session before a cadaver test. Eight adult fresh cadavers, 6 male and 2 female, were collected and randomly allocated to the 2 groups. Each group performed bilateral T11-L4 PSP on the cadavers independently, and the outcomes of PSP in terms of accuracy, success rate, and efficiency were assessed by computed tomography and compared between the 2 groups statistically. RESULTS: Accuracy rate of PSP in the VR group was 89.6% versus 60.4% in the non-VR group (P < 0.05), success rate was 100% versus 79.2% (P < 0.05), and mean time was 2.8 ± 1 minutes versus 4.9 ± 1 minutes (P < 0.05), all showing significant differences between the 2 groups. CONCLUSIONS: The immersive VR surgical simulator for PSP training model is superior to the traditional training model in terms of accuracy, success rate, and efficiency, showing potential in training new orthopedic spine surgeons.

iTRAQ-based quantitative proteomics reveals the biochemical mechanism of cold stress adaption of razor clam during controlled freezing-point storage.

Razor clam is a major cultivated shellfish of great economic importance and high nutritional value. Due to high corruptible potential, razor clam is generally preserved by controlled freezing-point storage (CFPS). Here, we applied isobaric tags for relative and absolute quantification (iTRAQ) labeling to investigate the biochemical mechanism of cold stress adaption in razor clam during CFPS. In total, 369 proteins were quantified, and 27 of them were identified as differentially expressed proteins during CFPS, mostly involved in energy metabolism process, DNA duplication and protein synthesis, and stress response, specifically, MAPK is the predominant pathway. Further qPCR results revealed H2A and S6K 2 alpha to be the critical post-transcriptionally regulated genes. Our results provided proteomics information with respect to the biochemical mechanism of cold stress adaption in razor clam, shed light on the further elongation of razor clams storage period, and help clarify the novel mechanisms of cold tolerance.

Intensity-modulated radiotherapy plus nimotuzumab with or without concurrent chemotherapy for patients with locally advanced nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of intensity-modulated radiotherapy (IMRT) plus nimotuzumab with or without concurrent chemotherapy (CCT) for patients with locally advanced nasopharyngeal carcinoma (LA-NPC). PATIENTS AND METHODS: A total of 50 newly diagnosed patients with LA-NPC treated at the Affiliated Hospital of Jiangnan University between November 2011 and January 2017 were retrospectively analyzed. All patients received the combined treatment modality of nimotuzumab plus IMRT. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Neoadjuvant, concurrent or adjuvant chemotherapy with the doublet regimen of taxanes (docetaxel or paclitaxel) plus platinum (cisplatin or nedaplatin) were administered. Among the 50 patients, 43 (86.0%) received ≥6 cycles of nimotuzumab (median 7 cycles, range 2-14 cycles) and 29 (58.0%) received two cycles of CCT with docetaxel plus nedaplatin. RESULTS: With a median follow-up of 28.0 months, the 2-year progression-free survival (PFS) and overall survival were 83.29% (95% confidence interval [CI]: 67.93%-91.72%) and 97.67% (95% CI: 84.62%-99.67%), respectively. Both univariate and multivariate analyses revealed that cycles of nimotuzumab were significantly associated with PFS. Patients who received ≥6 cycles of nimotuzumab showed a better PFS than those receiving <6 cycles (P=0.006), whereas the addition of CCT failed to improve PFS. Oral mucositis was the most common adverse event, which was recorded as grade 3-4 in 18 (36.0%) patients. Besides, two (4.0%) patients experienced nimotuzumab-related anaphylaxis, and no skin rash was found in any patient. Subgroup analysis revealed that the patients who received CCT had more grade 3-4 adverse events as compared to those who did not receive CCT (62.1% vs 33.3%, P=0.045). CONCLUSION: The regime of nimotuzumab plus IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC. Further clinical trials are needed to confirm these findings.

Biliverdin Protects the Isolated Rat Lungs from Ischemia-reperfusion Injury via Antioxidative, Anti-inflammatory and Anti-apoptotic Effects.

BACKGROUND: Biliverdin (BV) has a protective role against ischemia-reperfusion injury (IRI). However, the protective role and potential mechanisms of BV on lung IRI (LIRI) remain to be elucidated. Thus, we aimed to investigate the protective role and potential mechanisms of BV on LIRI. METHODS: Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model. After an initial 15 min stabilization period, the isolated lungs were subjected to ischemia for 60 min, followed by 90 min of reperfusion with or without BV treatment. RESULTS: Lungs in the I/R group exhibited significant decrease in tidal volume (1.44 ± 0.23 ml/min in I/R group vs. 2.41 ± 0.31 ml/min in sham group; P< 0.001), lung compliance (0.27 ± 0.06 ml/cmH2O in I/R group vs. 0.44 ± 0.09 ml/cmH2O in sham group; P< 0.001; 1 cmH2O=0.098 kPa), and oxygen partial pressure (PaO2) levels (64.12 ± 12 mmHg in I/R group vs. 114 ± 8.0 mmHg in sham group; P< 0.001; 1 mmHg = 0.133 kPa). In contrast, these parameters in the BV group (2.27 ± 0.37 ml/min of tidal volume, 0.41 ± 0.10 ml/cmH2O of compliance, and 98.7 ± 9.7 mmHg of PaO2) were significantly higher compared with the I/R group (P = 0.004, P< 0.001, and P< 0.001, respectively). Compared to the I/R group, the contents of superoxide dismutase were significantly higher (47.07 ± 7.91 U/mg protein vs. 33.84 ± 10.15 U/mg protein; P = 0.005) while the wet/dry weight ratio (P < 0.01), methane dicarboxylic aldehyde (1.92 ± 0.25 nmol/mg protein vs. 2.67 ± 0.46 nmol/mg protein; P< 0.001), and adenosine triphosphate contents (297.05 ± 47.45 nmol/mg protein vs. 208.09 ± 29.11 nmol/mg protein; P = 0.005) were markedly lower in BV-treated lungs. Histological analysis revealed that BV alleviated LIRI. Furthermore, the expression of inflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-ß) was downregulated and the expression of cyclooxygenase-2, inducible nitric oxide synthase, and Jun N-terminal kinase was significantly reduced in BV group (all P< 0.01 compared to I/R group). Finally, the apoptosis index in the BV group was significantly decreased (P < 0.01 compared to I/R group). CONCLUSION: BV protects lung IRI through its antioxidative, anti-inflammatory, and anti-apoptotic effects.

Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial.

Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received ≥6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab.

Segmentation of White Blood Cells Image Using Adaptive Location and Iteration.

Segmentation of white blood cells (WBCs) image is meaningful but challenging due to the complex internal characteristics of the cells and external factors, such as illumination and different microscopic views. This paper addresses two problems of the segmentation: WBC location and subimage segmentation. To locate WBCs, a method that uses multiple windows obtained by scoring multiscale cues to extract a rectangular region is proposed. In this manner, the location window not only covers the whole WBC completely, but also achieves adaptive adjustment. In the subimage segmentation, the subimages preprocessed from the location window with a replace procedure are taken as initialization, and the GrabCut algorithm based on dilation is iteratively run to obtain more precise results. The proposed algorithm is extensively evaluated using a CellaVision dataset as well as a more challenging Jiashan dataset. Compared with the existing methods, the proposed algorithm is not only concise, but also can produce high-quality segmentations. The results demonstrate that the proposed algorithm consistently outperforms other location and segmentation methods, yielding higher recall and better precision rates.

Automatic detection and classification of leukocytes using convolutional neural networks.

The detection and classification of white blood cells (WBCs, also known as Leukocytes) is a hot issue because of its important applications in disease diagnosis. Nowadays the morphological analysis of blood cells is operated manually by skilled operators, which results in some drawbacks such as slowness of the analysis, a non-standard accuracy, and the dependence on the operator's skills. Although there have been many papers studying the detection of WBCs or classification of WBCs independently, few papers consider them together. This paper proposes an automatic detection and classification system for WBCs from peripheral blood images. It firstly proposes an algorithm to detect WBCs from the microscope images based on the simple relation of colors R, B and morphological operation. Then a granularity feature (pairwise rotation invariant co-occurrence local binary pattern, PRICoLBP feature) and SVM are applied to classify eosinophil and basophil from other WBCs firstly. Lastly, convolution neural networks are used to extract features in high level from WBCs automatically, and a random forest is applied to these features to recognize the other three kinds of WBCs: neutrophil, monocyte and lymphocyte. Some detection experiments on Cellavison database and ALL-IDB database show that our proposed detection method has better effect almost than iterative threshold method with less cost time, and some classification experiments show that our proposed classification method has better accuracy almost than some other methods.

Kinetic resolution of racemic styrene oxide at a high concentration by recombinant Aspergillus usamii epoxide hydrolase in an n-hexanol/buffer biphasic system.

Using the cell-free extract of engineered E. coli/Aueh2, expressing the recombinant Aspergillus usamii epoxide hydrolase (reAuEH2), as a biocatalyst, the kinetic resolution technique of racemic styrene oxide (rac-SO) was examined. In a phosphate buffer system (50mM, pH 7.0), 200mM rac-SO was efficiently resolved, obtaining (S)-SO with 98.1% enantiomeric excess (e.e.), whereas (S)-SO only with 45.2% e.e. was obtained from 750mM rac-SO. The analytical results verified that reAuEH2 shows tolerance towards high substrate concentration but is inactivated at a product concentration of 300mM. To produce (S)-SO with the high concentration, e.e. and volumetric productivity, n-hexanol was selected from a variety of water-miscible and water-immiscible organic solvents to construct an n-hexanol/buffer biphasic system. The optimal phase volume ratio, substrate over enzyme ratio and temperature were 1:1 (v/v), 6:1 (w/w) and 25°C, respectively. In an optimized biocatalytic system, a gram-scale resolution of rac-SO at a high concentration of 1M (120g/L) was performed at 25°C for 2h, obtaining (S)-SO with 98.2% e.e., 34.3% yield (maximum yield of 50%). The substrate concentration and volumetric productivity (1M, 20.6g/L/h) in a biphasic system significantly increased compared with those (0.2M, 3.1g/L/h) in a phosphate buffer system. The efficient resolution of rac-SO at a high concentration in a biphasic system makes it a promising technique for preparing a highly value-added enantiopure (S)-SO with high volumetric productivity.