Application of immune cell infiltration in the diagnosis and prognosis of non-small cell lung cancer / 生物工程学报

Immune cell infiltration is of great significance for the diagnosis and prognosis of cancer. In this study, we collected gene expression data of non-small cell lung cancer (NSCLC) and normal tissues included in TCGA database, obtained the proportion of 22 immune cells by CIBERSORT tool, and then evaluated the infiltration of immune cells. Subsequently, based on the proportion of 22 immune cells, a classification model of NSCLC tissues and normal tissues was constructed using machine learning methods. The AUC, sensitivity and specificity of classification model built by random forest algorithm reached 0.987, 0.98 and 0.84, respectively. In addition, the AUC, sensitivity and specificity of classification model of lung adenocarcinoma and lung squamous carcinoma tissues constructed by random forest method 0.827, 0.75 and 0.77, respectively. Finally, we constructed a prognosis model of NSCLC by combining the immunocyte score composed of 8 strongly correlated features of 22 immunocyte features screened by LASSO regression with clinical features. After evaluation and verification, C-index reached 0.71 and the calibration curves of three years and five years were well fitted in the prognosis model, which could accurately predict the degree of prognostic risk. This study aims to provide a new strategy for the diagnosis and prognosis of NSCLC based on the classification model and prognosis model established by immune cell infiltration.

Effect of preoperative sleep deprivation on intestinal microflora of immunosuppressed mice after operation / 中华麻醉学杂志

Objective:To evaluate the effect of preoperative sleep deprivation on the intestinal microflora of immunosuppressed mice after operation.Methods:Seventy-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 23-25 g, were divided into 5 groups using a random number table method: operation group (group O, n=18), preoperative sleep deprivation group (group SR, n=18), pseudo germ-free mice orally treated with normal saline group (group GF+ V, n=12), pseudo germ-free mice that received fecal bacteria transplants from mice in group O group (group GF+ C, n=12), and pseudo germ-free mice that received fecal bacteria transplants from mice in group SR group (group GF+ SR, n=12). In group O and group SR, mice were subjected to sleep deprivation for 20 h every day for 7 consecutive days starting from 7 days before intraperitoneal exploration and partial liver lobectomy.Broad-spectrum antibiotics dissolved in drinking water were given ad libitum to C57BL/6 mice for 14 consecutive days starting from 2 weeks before operation to establish the pseudo germ-free mice model.Pseudo germ-free mice were gavaged with normal saline or fecal suspension (200 μl) obtained from mice at 24 h after surgery in group O and group SR.The fecal samples were collected at 24 h after operation for 16S rRNA gene sequence analysis.The longitudinal diameter and weight of the spleen were measured at 24 h after operation or fecal microbiota transplantation (FMT). CD4 + T cells, CD8 + T cells and regulatory T cells (Treg cells) were detected by flow cytometry. Results:Compared with group O, the Simpson diversity index of intestinal microflora was significantly decreased, the number of CD4+ T cells and CD8+ T cells in blood was decreased, the percentage of Treg cells was increased, and the longitudinal diameter and weight of the spleen were decreased in group SR, and the numbers of CD4 + and CD8 + cells in blood were significantly decreased, the percentage of Treg cells in blood was increased, and the longitudinal diameter and weight of the spleen were decreased in group GF+ V ( P<0.05). Compared with group GF+ V, the number of CD4 + T cells and CD8 + T cells in the blood was significantly increased, the percentage of Treg cells was decreased, and the longitudinal diameter and weight of the spleen were increased in group GF+ O ( P<0.05). Compared with group GF+ O, the number of CD4+ T cells and CD8+ T cells in blood was significantly decreased, the percentage of Treg cells was increased, and the longitudinal diameter and weight of the spleen were decreased in group GF+ SR ( P<0.05). Conclusion:The mechanism by which preoperative sleep deprivation accentuates postoperative immunosuppression is related to the intestinal microflora disorder in mice.

Role of intestinal flora disturbance in perioperative neurocognitive disorders in aged mice / 中华麻醉学杂志

Objective@#To evaluate the role of intestinal flora disturbance in perioperative neurocognitive disorders in aged mice.@*Methods@#Sixty SPF healthy male C57BL/6J mice, aged 18 months, were divided into 4 groups (n=15 each) by a random number table method: control group (group C), operation group (group O), operation plus lactobacillus rhamnosus group (group OL) and operation plus fecal microbiota transplantation group (group OF). Exploratory laparotomy was performed in O, OL and OF groups.In group PL, lactobacillus rhamnosus 200 μl (1×109 CFU/ml, 200 μl/day) was given by gavage once a day for 10 days starting from the end of surgery, and mice received about 0.2×109 CFU probiotics per day.In group OF, broad-spectrum antibiotic mixture (ampicillin and sulbactam 1.5 g/L, vancomycin 500 mg/L, ciprofloxacin 200 mg/L, imipenem cilastatin 250 mg/L and metronidazole 1 g/L) was added to the drinking water at 7 weeks prior to operation and replaced with sterile tap water at 72 h before operation, and fecal filtrates 200 μl was given by gavage once a day for 10 days starting the end of operation.Five mice were sacrificed at day 10 after operation in each group, and Evans blue extravasation test was used to measure the vascular permeability of jejunum and ileum.Five mice were sacrificed at day 10 after operation in each group, and the small intestinal and hippocampal tissues and orbital venous blood samples were obtained for determination of interleukin-6 (IL-6), IL-17, tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), IL-4 and IL-10 levels by enzyme-linked immunosorbent assay.Five mice were selected at day 10 after operation in each group, and the Morris water maze test was used to assess the cognitive function.@*Results@#Compared with group C, the vascular permeability of jejunum and ileum was significantly increased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus were increased, the levels of IL-4 and IL-10 were decreased, the swimming distance and escape latency were prolonged, and the time spent in the target quadrant was shortened in group O (P<0.05 or 0.01), and no significant change was found in the parameters mentioned above in OL and OF groups (P>0.05). Compared with group O, the vascular permeability of jejunum and ileum was significantly decreased, the levels of IL-6, IL-17, TNF-α and IFN-γ in the small intestine, peripheral blood and hippocampus were decreased, the levels of IL-4 and IL-10 were increased, the swimming distance and escape latency were shortened, and the time spent in the target quadrant was prolonged in OL and OF groups (P<0.05).@*Conclusion@#Intestinal flora disturbance can mediate inflammatory responses in the hippocampus and cause perioperative neurocognitive disorders in aged mice.

Role of intestinal flora disturbance in perioperative neurocognitive disorders in aged mice / 中华麻醉学杂志

Objective To evaluate the role of intestinal flora disturbance in perioperative neurocognitive disorders in aged mice.Methods Sixty SPF healthy male C57BL/6J mice,aged 18 months,were divided into 4 groups (n =15 each) by a random number table method:control group (group C),operation group (group O),operation plus lactobacillus rhamnosus group (group OL) and operation plus fecal microbiota transplantation group (group OF).Exploratory laparotomy was performed in O,OL and OF groups.In group PL,lactobacillus rhamnosus 200 μl (1×109 CFU/ml,200 μl/day) was given by gavage once a day for 10 days starting from the end of surgery,and mice received about 0.2× 109 CFU probiotics per day.In group OF,broad-spectrum antibiotic mixture (ampicillin and sulbactam 1.5 g/L,vancomycin 500 mg/L,ciprofloxacin 200 mg/L,imipenem cilastatin 250 mg/L and metronidazole 1 g/L) was added to the drinking water at 7 weeks prior to operation and replaced with sterile tap water at 72 h before operation,and fecal filtrates 200 μl was given by gavage once a day for 10 days starting the end of operation.Five mice were sacrificed at day 10 after operation in each group,and Evans blue extravasation test was used to measure the vascular permeability of jejunum and ileum.Five mice were sacrificed at day 10 after operation in each group,and the small intestinal and hippocampal tissues and orbital venous blood samples were obtained for determination of interleukin-6 (IL-6),IL-17,tumor necrosis factor-alpha (TNF-α),interferon gamma (IFN-γ),IL-4 and IL-10 levels by enzyme-linked immunosorbent assay.Five mice were selected at day 10 after operation in each group,and the Morris water maze test was used to assess the cognitive function.Results Compared with group C,the vascular permeability of jejunum and ileum was significantly increased,the levels of IL-6,IL-17,TNF-α and IFN-γ in the small intestine,peripheral blood and hippocampus were increased,the levels of IL-4 and IL-10 were decreased,the swimming distance and escape latency were prolonged,and the time spent in the target quadrant was shortened in group O (P＜0.05 or 0.01),and no significant change was found in the parameters mentioned above in OL and OF groups (P＞0.05).Compared with group O,the vascular permeability of jejunum and ileum was significantly decreased,the levels of IL-6,IL-17,TNF-α and IFN-γin the small intestine,peripheral blood and hippocampus were decreased,the levels of IL-4 and IL-10 were increased,the swimming distance and escape la tency were shortened,and the time spent in the target quadrant was prolonged in OL and OF groups (P＜0.05).Conclusion Intestinal flora disturbance can mediate inflammatory responses in the hippocampus and cause perioperative neurocognitive disorders in aged mice.

Kinematics parameter identification and accuracy evaluation method for neurosurgical robot / 生物医学工程学杂志

The kinematic model parameter deviation is the main factor affecting the positioning accuracy of neurosurgical robots. To obtain more realistic kinematic model parameters, this paper proposes an automatic parameters identification and accuracy evaluation method. First, an identification equation contains all robot kinematics parameter was established. Second, a multiple-pivot strategy was proposed to find the relationship between end-effector and tracking marker. Then, the relative distance error and the inverse kinematic coincidence error were designed to evaluate the identification accuracy. Finally, an automatic robot parameter identification and accuracy evaluation system were developed. We tested our method on both laboratory prototypes and real neurosurgical robots. The results show that this method can realize the neurosurgical robot kinematics model parameters identification and evaluation stably and quickly. Using the identified parameters to control the robot can reduce the robot relative distance error by 33.96% and the inverse kinematics consistency error by 67.30%.

Role of intestinal flora disturbance in development of POCD in aged mice: the relationship with Treg and Th1/Th2 cells in small intestine / 中华麻醉学杂志

Objective To evaluate the role of intestinal flora disturbance in development of postoperative cognitive dysfunction (POCD) in aged mice and the relationship with regulatory T cells (Treg) and T helper cells 1/T helper cells 2 (Th1/Th2) in the small intestine.Methods Thirty-six SPF healthy male C57BL/6J mice,weighing 45-50 g,aged 18 months,were divided into 3 groups (n=12 each) using a random number table method:control group (group C),POCD group and POCD plus VSL#3 group (group PV).POCD was induced by abdominal exploration.VSL#3 probiotics was given by intragastric gavage (300 μl per time,once a day) every 24 h for 7 consecutive days starting from the end of surgery in group PV.Morris water maze test was used to assess the cognitive function at day 7 after operation.Orbital venous blood samples were collected after the end of Morris water maze test,and animals were then sacrificed and small intestine and hippocampi were removed for measurement of the percentage of CD4+ CD25+ Foxp3+Treg,TCD4+IFN-γ+Th1 and CD4+IL-4+Th2 in the lamina propria of small intestine and plasma and expression of IL-4 and IFN-γmRNA in the lamina propria of small intestine,plasma and hippocampal tissues,and IL-4 mRNA/IFN-γmRNA ratio was calculated.Results Compared with group C,the percentage of CD4+CD25+Foxp3+Treg and CD4+IL-4+ Th2 in the lamina propria of small intestine and plasma was significantly decreased,the percentage of CD4+ IFN-γ+Th1 in the lamina propria of small intestine and plasma was increased,the expression of IL-4 mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was down-regulated,the expression of IFN-γ mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was up-regulated,IL-4 mRNA/IFN-γ mRNA ratio was decreased,the escape latency and swimming distance were prolonged,and the time spent in the target quadrant was shortened in group POCD (P＜0.05).Compared with group POCD,the percentage of CD4+ CD25+ Foxp3+ Treg and CD4+IL-4+ Th2 in the lamina propria of small intestine and plasma was significantly increased,the percentage of CD4+IFN-γ+Th1 in the lamina propria of small intestine and plasma was decreased,the expression of IL-4 mRNA in the lamina propria of small intestine,plasma and hippocampal tissues was upregulated,the expression of IFN-γmRNA in the lamina propria of small intestine,plasma and hippocampal tissues was down-regulated,IL-4 mRNA/IFN-γmRNA ratio was increased,the escape latency and swimming distance were shortened,and the time spent in the target quadrant was prolonged in group PV (P＜ 0.05).Conclusion Intestinal flora disturbance can promote the development of POCD in aged mice,which is related to the decreased percentage of Treg and Th1/Th2 imbalance in the small intestine.

Roles of transient receptor potential melastatin 7 in hippocampal neuron injury / 临床麻醉学杂志

Objective To investigate the role of transient receptor potential melastatin 7 (TR PM7) in the protective role of sevoflurane preconditioning against hippocampal neuron injury caused by oxygen glucose deprivation (OGD).Methods Hippocampal neurons were harvested from postnatal day 1 SD rats,and randomly divided into 5 groups:control group (group C),sevoflurane group (group Sev),oxygen-glucose deprivation group (group OGD),sevoflurane+ OGD group (group SD) and sevoflurane+OGD+bradykinin group (group B).To build up the model of OGD,the neurons were cultured in a deoxygenated glucose-free medium and exposed to 95％ N2 and 5％％ CO2 in an anaerobic chamber equilibrated at 37℃ for 1.5 h,followed by replacement with glucose containing medium and return to a standard incubator for additional 24 h.The neurons in group C received no treatment.Group OGD was preconditioned with 2 ％ sevoflurane for 1 h.The neurons in group OGD were subjected to OGD.Group SD was preconditioned with 2％ sevoflurane for 1 h,followed by OGD at 24 h after the sevoflurane exposure.The neurons in group B was incubated in a medium supplemented with 200 μmol/L bradykinin (the selective agonist of TRPM7),followed sequen tially by the preconditioning of 2％ sevoflurane for 1 h and then OGD challenge.Twenty-four hours after re-oxygenation,The relative neuronal cell viability was determined by MTT assay,the neuronal apoptotic rate was analyzed by TUNEL assay,the protein expression of TRPM7 was detected by Western blot,the mRNA level of TRPM7 was estimated by real-time PCR,the neuronal release of IL-1β and TNF-α in the serum was measured by ELISA.Results Compared with group C,the mR NA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL-1β and TNFα were significantly up-regulated in group OGD (P＜0.05),whereas the cell viability was decreased (P＜0.05).Compared with group OGD,the mRNA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL1β and TNF-α were significantly down-regulated in group SD (P＜0.05),whereas the cell viability was increased (P＜0.05).Compared with group SD,the mRNA and protein levels of TRPM7,the neuronal apoptotic rate,the mRNA and supernatant protein levels of IL-1β and TNF-α were significantly up-regula ted in group B (P＜0.05),whereas the cell viability was decreased (P＜0.05).Conclusion Sevoflurane attenuates apoptosis and inflammatory responses induced by OGD via reduction of the overex pression of TRPM7 in the hippocampal neurons.

Effect of dexmedetomidine on nerve regeneration following cerebral ischemia-reperfusion in mice:the role of TGF-β1 in brain tissues / 中华麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on nerve regeneration following cerebral ischemia-reperfusion (Ⅰ/R) in mice and the role of transforming growth factor-beta 1 (TGF-β1) in brain tissues.Methods Sixty healthy SPF male C57BL/6J mice,weighing 23-25 g,aged 8-10 weeks,were divided into 5 groups (n =12 each) using a random number table method:sham operation group (group Sham),Ⅰ/R group,dexmedetomidine group (group D),dexmedetomidine plus IgG1 isotype control monoclonal antibody group (group DI) and dexmedetomidine plus TGF-β1 neutralizing monoclonal antibody group (group DA).Cerebral Ⅰ/R was induced by occlusion of the middle cerebral artery followed by reperfusion.Dexmedetomidine 50 μg/kg was intraperitoneally injected every 24 h for 14 days starting from 14 days of reperfusion in group D.TGF-β1 neutralizing monoclonal antibody 20 μg and IgG1 isotype control monoclonal antibody 20 μg were intraperitoneally injected at 30 min prior to dexmedetomidine injection in group DA and group DI,respectively.5-bromodeoxyuridine (BrdU) 100 mg/kg was intraperitoneally injected and injected again at an 8-h interval on 27 days of reperfusion.Forced swimming test (FST),sucrose consumption test (SCT) and open field test (OFT) were performed at 16 h after the second administration of BrdU.After the end of behavior testing,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone on ischemic side was measured by immunohistochemistry,and the expression of TGF-β1 protein and mRNA in brain tissues in ischemic area was detected using Western blot and real-time polymerase chain reaction,respectively.Results Compared with group Sham,the time spent floating in FST was significantly prolonged,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were decreased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was increased,and the expression of TGF-β1 protein and mRNA was up-regulated in group Ⅰ/R (P＜0.05 or 0.01).Compared with group Ⅰ/R,the time spent floating in FST was significantly shortened,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were increased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was increased,and the expression of TGF-β1 protein and mRNA was up-regulated in group D (P＜0.05 or 0.01).Compared with group D,the time spent floating in FST was significantly prolonged,the percent of time spent in the central region in OFT and sucrose solution intake in SCT were decreased,the number of Ki67,BrdU and BrdU/DCX positive cells in the subventricular zone was decreased in group DA (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group DI (P＞0.05).Conclusion Dexmedetomidine can relieve depression and anxiety following cerebral Ⅰ/R,thus promotes nerve regeneration and the mechanism is related to up-regulating the expression of TGF-β1 in brain tissues of mice.

Clinical application of extended nursing in asthmatic children with allergic rhinitis / 中国实用护理杂志

Objective@#To evaluate the effects of extended nursing mode on the asthmatic children with allergic rhinitis (AR).@*Methods@#Totally116 children aged 6-14 years old with asthma and AR were enrolled to this study from November 2015 to October 2016 in our hospital. They were divided into the regular nursing group and the extended nursing group according to the voluntary principle. The patients in regular nursing group were received routine nursing care in or out of hospital, while the patients in extended nursing group received extended care besides routine nursing. The children were required to record diary about asthma and AR And participate in asthma action projects. Before and after intervention we observed the quantitative score of symptoms and signs, the times of acute attack, the times of oblivion medication, the average days of stay in hospital, the days of fail to School or kindergarten, the lung function and the fractional exhaled nitric oxide (FeNO) in children with asthma and AR within 1 year. These above marks were assessed five times respectively at starting (baseline) , 3 months, 6 months, 9 months and 12 months (1 year) The differences between two groups were compared with appropriate statistical methods.@*Results@#1 year later, out of 58 cases in extended nursing group, 40 patients (68.97%)were in good control and 18 cases (31.03%) in partial control. Out of 58 cases in regular nursing group, 22 cases (37.93%) were in good control and 36 patients (62.07%) in partial control. There were significant differences between two groups in the effect of disease (χ2=11.23, all P<0.01), the experimental group was significantly better than the control group. The symptoms and signs of allergic rhinitis average scores in regular nursing group were 1.88 ± 0.72, extended nursing group were 0.79 ± 0.71, the difference was statistically significant (t=8.080, P<0.01) with the extended nursing group much better that the regular nursing group. The symptoms and signs of asthma average scores in regular nursing group were1.83 ± 0.75, extended nursing group were 0.88 ± 0.67, the difference was also statistically significant (t=7.133, P<0.01) with the extended nursing group much better that the regular nursing group. In extended nursing groups within 1 year the numbers of acute attack (0.60±0.59), the times of oblivion medication (11.05±7.40), the average days of stay in hospital (8.83±2.79) days,the average days of failing to school or kindergarten (8.69±5.46) days, while in regular nursing group within 1 year the numbers of acute attack(2.94±1.52), the times of oblivion medication (35.28±8.84), the average days of stay in hospital(20.95±5.46 days), the average days of fail to school or kindergarten(24.72±5.92) days, the differences were also statistically significant (t=10.50-15.87, P<0.01). The lung function in extended nursing group (PEF: 82.02±6.04, FEVI: 88.19±5.10, FEV25: 80.67±4.88, FEV50: 80.07±3.73, FEV75: 81.52±3.85) and in regular nursing group (PEF: 79.02±6.12,, FEV1: 80.52±4.72, FEV25: 75.05±7.79, FEV50: 77.59±4.60, FEV75: 78.41±4.19) . The differences were also statistically significant (t=2.90-6.15, P<0.01).The FeNO(13.66±2.87) ppb in extended nursing group and (14.95±3.12) ppb in regular nursing group. There were statistical significant differences between the two groups (t=2.30, P<0.05) with extended nursing group much better than regular nursing group.@*Conclusion@#The effect of extended care group is better than that of regular nursing group, and extended care is much more benefit to control asthma and allergic rhinitis in children.

Establishment of metastatic colorectal cancer patient-derived xenografts models by image-guided biopsy / 中国癌症杂志

Background and purpose: Current colorectal cancer patient-derived xenografts (PDXs) models were established by samples taken during surgery. However, metastatic colorectal cancer (mCRC) patients have less surgical opportunities, and it was difcult to obtain enough tumor fragment. The aim of the present study was to es-tablish mCRC PDXs by image-guided biopsy. Methods: A total of 12 patients with colorectal cancer who underwent surgery were included. All patients had recurrent lesions or metastatic lesions needed to be histologically confirmed, and none of them had contraindication to biopsy. Tumor tissues not required for clinical diagnosis were used to establish mCRC PDXs. Results: Seven PDXs grew sufficiently for transfer into mice. The success rate was 77.8%. Conclusion:The PDXs established by image-guided biopsy had the advantage of convenient operation, good reproducibility, high achievement ratio, short experimental periodicity and reliably retain specific genetic and morphological features of the primary patient tumors.

Effect of cardamonin on acute lung injury induced by hemorrhagic shock and resuscitation in rats / 中华麻醉学杂志

Objective To evaluate the effect of cardamonin on acute lung injury induced by hemorrhagic shock and resuscitation (HSR) in rats.Methods Thirty-two male Sprague-Dawley rats,aged 18-24 weeks,weighing 200-250 g,were divided into 4 groups (n =8 each) using a random number table:sham operation group (group Sham);group HSR;cardamonin group (group CA);cardamonin + adenosina A2A receptor antagonist ZM241385 group (group CZM).Bilateral common carotid arteries were only cannulated in group Sham.The left common carotid artery was cannulated for blood-letting until mean arterial pressure was reduced to 35-45 mmHg and maintained at this level for 30 min,and the animals were then resuscitated by infusion of shed blood and normal saline two-fold volume of shed blood to establish HSR model in HSR,CA and CZM groups.ZM241385 5 mg/kg was injected intraperitoneally at 30 min before blood-letting in group CZM,and cardamonin 75 mg/kg was injected intraperitoneally immediately after the beginning of resuscitation in CA and CZM groups.The rats were sacrificed at 2 h after completion of resuscitation,bronchoalveolar lavage fluid (BALF) was collected for determination of neutrophil count,and lungs were removed for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio),contents of tumor necrosis factor-alpha (TNF-ct),interleukin-1 (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and expression of adenosine A2A receptors in lung tissues (by Western blot).Results Compared with group Sham,the neutrophil count in BALF,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly increased,the expression of adenosine A2A receptors was significantly down-regulated in group HSR,and the neutrophil count in BALF and contents of TNF-α and IL-6 were significantly increased (P＜0.05),and no significant changes were found in W/D ratio,content of IL-1β,and expression of adenosine A2A receptors in group CA (P＞0.05).Compared with group HSR,the neutrophil count in BALF,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly decreased,the expression of adenosine A2A receptors was significantly up-regulated (P＜0.05),and the pathological changes were significantly attenuated in group CA,and no significant changes were found in the parameters mentioned above in group CZM (P＞0.05).Compared with group CA,the neutrophil count in BALF,W/D ratio and contents of TNF-α,IL-1β and IL-6 were significantly increased,the expression of adenosine A2A receptors was significantly down-regulated (P＜0.05),and the pathological changes were aggravated in group CZM.Conclusion Cardamonin can attenuate acute lung injury induced by HSR in rats,and activated adenosine A2A receptors and inhibited inflammatory responses are involved in the mechanism.

A new kinematics method of determing elbow rotation axis and evaluation of its feasi-bility / 北京大学学报(医学版)

Objective:To study a new positioning method of elbow external fixation rotation axis,and to evaluate its feasibility.Methods:Four normal adult volunteers and six Sawbone elbow models were brought into this experiment.The kinematic data of five elbow flexion were collected respectively by opti-cal positioning system.The rotation axes of the elbow joints were fitted by the least square method.The kinematic data and fitting results were visually displayed.According to the fitting results,the average moving planes and rotation axes were calculated.Thus,the rotation axes of new kinematic methods were obtained .By using standard clinical methods,the entrance and exit points of rotation axes of six Sawbone elbow models were located under X-ray.And The kirschner wires were placed as the representatives of rotation axes using traditional positioning methods.Then,the entrance point deviation,the exit point de-viation and the angle deviation of two kinds of located rotation axes were compared.Results:As to the four volunteers,the indicators represented circular degree and coplanarity of elbow flexion movement tra-jectory of each volunteer were both about 1 mm.All the distance deviations of the moving axes to the ave-rage moving rotation axes of the five volunteers were less than 3 mm.All the angle deviations of the mo-ving axes to the average moving rotation axes of the five volunteers were less than 5 °.As to the six Saw-bone models,the average entrance point deviations,the average exit point deviations and the average angle deviations of two different rotation axes determined by two kinds of located methods were respective-ly 1.697 2 mm,1.838 3 mm and 1.321 7°.All the deviations were very small.They were all in an ac-cep-table range of clinical practice.Conclusion:The values that represent circular degree and coplanari-ty of volunteer's elbow single curvature movement trajectory are very small.The result shows that the elbow single curvature movement can be regarded as the approximate fixed axis movement.The new method can replace the traditional method in accuracy.It can make up the deficiency of the traditional fixed axis method.

Effect of BML-111 on ventilator-induced lung injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of BML?111 on ventilator?induced lung injury in rats. Methods Forty?eight healthy male Sprague?Dawley rats, weighing 200-250 g, aged 6-8 weeks, were randomized into 6 groups ( n=8 each) using a random number table: control group ( C group) , low tidal volume (VT) group (LVTgroup), high VT group (HVTgroup), low dose BML?111 group (BL group), high dose BML?111 group ( BH group) , and BML?111 plus BOC?2 ( lipoxin A4 receptor antagonist) group ( BOC?2 group) . Group C kept spontaneous breathing after tracheotomy, and received no mechanical venti?lation. The rats in the other 5 groups were mechanically ventilated ( respiratory rate 80 breaths∕min, frac? tion of inspired oxygen 21%, positive end?expiratory pressure 0) . The VT was 6 ml∕kg in group LVT , or 20 ml∕kg in HVT, BL, BH and BOC?2 groups. BML?111 0?1 and 1?0 mg∕kg were injected intraperitoneally during ventilation in BL and BH groups, respectively. In group BOC?2, BOC?2 50 μg∕kg was injected in?traperitoneally before ventilation, and BML?111 1?0 mg∕kg was injected intraperitoneally during ventilation. Arterial blood samples were collected at 4 h of ventilation, arterial oxygen partial pressure ( PaO2 ) was de?termined. Then animals were sacrificed by exsanguination. Bronchoalveolar lavage fluid ( BALF) of the left lung was collected for determination of neutrophil count, and the level of neutrophil was calculated. The right lung tissue specimens were obtained for microscopic examination, and for determination of wet∕dry lung weight ratio ( W∕D ratio ) , myeloperoxidase ( MPO ) activity, and contents of malondialdehyde ( MDA) , monocyte chemoattractant protein?1 ( MCP?1) , tumor necrosis factor?alpha ( TNF?α) , interleu?kin?1beta ( IL?1β) and IL?6. Results Compared with group C, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group HVT ( P0?05) . Compared with group HVT , PaO2 was significantly increased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were decreased in group BH, and the contents of TNF?α, IL?1βand IL?6 were significantly decreased ( P0?05) . Compared with group BH, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group BOC?2 (P<0?05). The pathological changes were significantly attenuated in group BL as compared with HVT and BOC?2 groups. Conclusion BML?111 can attenuate ventilator?induced lung injury in rats, and activated lipoxin A4 receptors are involved in the mechanism.

Sirtuin 1-mediated inhibition of p66shc expression alleviates liver ischemia/reperfusion injury.

OBJECTIVES: Ischemia/reperfusion is a leading cause of liver damage after surgical intervention, trauma, and transplantation. It has been reported that the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 attenuates myocardial, cerebral, and renal ischemia/reperfusion damage. This study aimed to investigate the involvement of sirtuin 1-mediated p66shc inhibition in liver ischemia/reperfusion and explore the effect of carnosic acid and ischemic preconditioning on liver ischemia/reperfusion-induced damage. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats and HepG2 cells. INTERVENTIONS: The rats were subjected to 45 minutes of ischemia to 70% of the liver, followed by 3-hour reperfusion. The HepG2 cells were subjected to hypoxia/reoxygenation-induced injury. MEASUREMENTS AND MAIN RESULTS: In the rats with liver ischemia/reperfusion injury, carnosic acid pretreatment and ischemic preconditioning dramatically reduced the serum aminotransferase activity and proinflammatory chemokine levels and improved the liver histological evaluations. Carnosic acid and ischemic preconditioning also increased manganese superoxide dismutase and Bcl-xL, but down-regulated cleaved caspase-3. Interestingly, the protective effect of carnosic acid and ischemic preconditioning was positively associated with sirtuin 1 activation. By contrast, p66shc, a kinase that promotes oxidative injury and apoptosis, was inhibited by carnosic acid and ischemic preconditioning. Sirtuin 1 small interfering RNA knockdown experiments confirmed that carnosic acid increased sirtuin 1-mediated repression of p66shc in HepG2 cells and that the protective effect of carnosic acid against hypoxia/reoxygenation injury was inhibited by the sirtuin 1 inhibitor nicotinamide. These results suggest that carnosic acid protects hepatocytes from hypoxia/reoxygenation damage through sirtuin 1-mediated p66shc suppression. To support this notion, we further demonstrated that the sirtuin 1 activator resveratrol achieved a protective effect similar to that of carnosic acid against hypoxia/reoxygenation injury, whereas sirtuin 1 small interfering RNA and nicotinamide had the opposite effect. CONCLUSIONS: Carnosic acid and ischemic preconditioning protect against ischemia/reperfusion-induced liver injury. Mechanistically, the protective effect involves the sirtuin 1-mediated inhibition of p66shc, suggesting that this pathway is a novel potential therapeutic target for protecting the liver from ischemia/reperfusion injury.

Effect of BML-111 on acute lung injury induced by hemorrhagic shock and resuscitation in rats / 中华麻醉学杂志

Objective To evaluate the effect of lipoxin A4 receptor agonist BML-111 on acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-250 g,were randomized into 4 groups (n =8 each) using a random number table:sham operation group (S group),hemorrhagic shock/resuscitation group (HSR group),BML-111 group,and BML-111 plus BOC-2 (lipoxin A4 receptor antagonist) group (BOC-2 group).The animals were anesthetized with 2％ pentobarbital sodium 80 mg/kg,tracheostomized and mechanically ventilated.Left common carotid artery was cannulated for blood-letting and fluid infusion.Hemorrhagic shock was induced according to the method described by Kochanek et al.MAP was reduced to 35-45 mmHg and maintained at this level for 30 min.The animals were then resuscitated for 30 min with infusion of the blood withdrawn and lactated Ringer' s solution 2 times the volume of blood withdrawn.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.In BOC-2 group,BOC-2 (50 μg/kg) was injected intraperitoneally before blood-letting.The rats were sacrificed at 2 h after completion of resuscitation.Bronchoalveolar lavage fluid (BALF) was collected for determination of neutrophil count.Lungs were excised for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio),contents of interleukin-1 (IL-1β) and IL-6,and phosphorylation of mitogen-activated protein kinase (MAPK).Results Compared with group S,the neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly increased in HSR group (P ＜ 0.05).The neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly lower in BML-111 group than in HSR group,and higher in BOC-2 group than in BML-111 group (P ＜ 0.05).Conclusion BML-111 can attenuate acute lung injury induced by hemorrhagic shock and resuscitation in rats and inhibition of activation of MAPK pathways and reduction of inflammatory responses in lung tissues are involved in the mechanism.

A method of generating synthetic medical image for the validation of segmentation algorithms / 国际生物医学工程杂志

Objective To develop a synthetic medical image generation system which can provide test images for the validation of medical image segmentation algorithms.Methods The synthetic image was created based on the deformation of region of interest (ROI) in original clinical images.First the synthetic foreground boundarywas generated by the resampling of the Fourier descriptors of manually segmented foreground boundary in original image.Then all the ROI pixels were divided into 4 categories and their intensities were calculated by texture matching techniques.Results The intracranial hemorrhage image was selected as the original image,and the generated synthetic images were applied to validate the precision and accuracy of multi-threshold segmentation and level set algorithm.Conclusion The proposed system can rapidly generate synthetic images with realistic appearance of clinical cases and well define ground truth foreground boundary.It has strong practicality for quantitative validation of segmentation algorithms.

A kinematic study of the tibiofemoral joint after total knee arthroplasty using in vivo fluoroscopy and digital model / 中华骨科杂志

Objective To investigate the relative motion between the femoral component and the tibial insert through the technology of fluoroscopy and digital model.Methods Sixteen female patients (16 knees) with knee osteoarthritis were performed TKA (GENESIS Ⅱ) from July 2007 to June 2008.The mean age was 66.4 years (range from 56 to 76 years).All patients were followed up 48 months to 60 months,with the mean of 56±3 months.The postoperative clinical function was evaluated by Knee Society Score (KSS).To match the digital model to the imaging data of fluoroscopy using 2D-3D automatic registration technology and reconstruct motion of the knee after TKA.The movement of contact position between femoral medial and lateral condyle and tibial insert and tibial internal rotation during flexion were measured.The contact time and range between femoral cam and tibial post were analyzed.Results The cases were statistically improved in KSS postoperatively,knee score was 93±5 and function score 88±13.The range of movement for femoral medial condyle was 8.5±2.5 mm,and the lateral condyle was 9.5±4.8 mm,the range of tibial internal rotation was 2.5°±8.4°.The contact of cam and post was observed after 30°-40° flexion of the knee,and the range was 8.0±1.8 mm.The greater tilting angle of the tibial plateau was,the later contact between cam and post happened.Conclusion The kinematics of tibiofemoral joint after TKA is different from the kinematics of normal knee.With knee flexion within 10°-30°,femoral medial condyle moves forward.When flexion is greater than 40°,medial and lateral condyle begins rollback.The time of contact of cam and post is relative to tibial prosthesis slope.

Olfactory ensheathing cells transplantation for brain injury:Feasibility analysis and effect validation / 中国组织工程研究

BACKGROUND:Brain injury is a serious central nervous system trauma.However,it is difficult to promote nerve regeneration and functional recovery after brain injury.Sheath cells are conducive to neuronal survival and axonal regeneration.OBJECTIVE:To explore feasibility and effect of olfactory ensheathing cells transplantation on rat brain injury.METHODS:A total of 90 healthy adult male SD rats were selected and 10 were used to prepare olfactory ensheathing cells.The remaining were randomly divided into model control and transplantation groups with 40 animals in each group.Model of middle cerebral artery occlusion was established by thread method.At 1 week,2×10~6 suspension of olfactory sheath cells and an equal volume of sterile saline were injected into two groups,respectively via the carotid artery.Neurological deficits were evaluated by creeping scores;histopathological changes were detected by HE staining,and glial fibrillary acidic protein and neurotrophic factor receptor p75 expression was detected by immunohistochemistry.RESULTS AND CONCLUSION:Compared with the model control group,the neurological deficit scores were significantly reduced in the transplantation group compared with the control group at 1,2,3,and 4 weeks following cerebral ischemia/reperfusion(P ＜ 0.05);the pathological changes in injured brain tissues were ameliorated,the number of nerve cell degeneration and necrosis was significantly reduced,and edema was attenuated.A great amount of glial fibrillary acidic protein and neurotrophic factor receptor p75 expression was detected in the infarct hemisphere following cell transplantation,and little in the contralateral hemisphere and vascular endothelial cells.Negative expression was detected in the model control group.Results show that the olfactory ensheathing cell transplantation is effective on ischemic brain injury in the rats.

Electrophysiological changes and hindlimb motor function of a model rat with spinal cord injury following olfactory ensheathing cell transplantation / 中国组织工程研究

BACKGROUND: Previous research has proved that olfactory ensheathing cells can promote neuronal survival and axonal regeneration. OBJECTIVE: To investigate the effect of olfactory ensheathing cell transplantation on the treatment of spinal cord injury of rats. METHODS: A total of 40 healthy adult female SD rats were randomly divided into control and cell transplantation groups, with 20 rats for each group. Ten additional SD rats were used for separation and culture of olfactory ensheathing cells. Spinal cord injury was induced in both control and cell transplantation groups. 2-cm bilateral 8th-10th intercostal nerves were crossly implanted into spinal cord defect region, i.e., proximal white matter and distal gray matter, distal white matter and proximal gray matter. Olfactory ensheathing cells at density of 2×10~6 were locally injected into cell transplantation group, while an equal amount saline was locally injected into control group. Somatosensory evoked potential and motion evoked potential were detected to observe neuro-electrophsiological recovery; BBB was used to evaluate hindlimb motor function; BDA anterograde tracer was used to observe motor conduction recovery. RESULTS AND CONCLUSION: Latency and amplitude of somatosensory evoked potential and motion evoked potential in the cell transplantation group were significantly greater than control group (P < 0.01). BBB scores of cell transplantation group were significantly greater than control group (P < 0.01). BDA-positive nerve fibers in the cell transplantation group were significantly more than control group (P < 0.01). Local injection of olfactory ensheathing cells can improve neuro-electrophysiological changes and promote hindlimb motor functional recovery following spinal cord injury.

Local injection of embryonic neural stem cells for treatment of experimental spinal cord injury: Evaluation of somatosensory and motor evoked potentials and hind limb motor function / 中国组织工程研究

BACKGROUND: To improve neural regeneration and functional recovery following spinal cord injury (SCI) remains difficult. Embryonic neural stem cells benefit neuronal survival and promote axonal regeneration.OBJECTIVE: To explore the feasibility of the local injection of embryonic neural stem cells to treat rats with high level SCI, and evaluate its effect by neuroelectrophysiology and motor function of hind limbs.DESIGN, TIME AND SETTING: In vivo experiment of cytology was performed at the Animal Experimental Center of Harbin Medical University from June 2007 to June 2008.MATERIALS: A total of 40 healthy adult SD rats were randomly divided into two groups (n=20): normal saline and cell transplantation groups. In addition, 5 SD rats, pregnant 14 days, were used for preparation of embryonic neural stem cells.METHODS: High level SCI was made in two groups. Briefly, 2 cm of bilateral intercostal nerves respectively from the 8~(th) to 10~(th) costal bones was crossing implanted in the SCI (proximal white matter and distal gray matter; distal white matter and proximal gray matter). Cell transplantation group was locally injected with 2×10~6 embryonic neural stem cells, and normal saline group was injected with the same volume of normal saline.MAIN OUTCOME MEASURES: Somatosensory evoked potential (SEP) and motor evoked potentials (MEP) testing, observation of the recovery of neuroelectrophysiology; BDA anterograde neural tracer; the recovery of motor conduction by the main beam;BBB hind limb motor function score.RESULTS: SEP and MEP latency and amplitude of cell transplantation group were better than normal saline group (P < 0.01).BDA-positive nerve fibers through the tag were found in cell transplantation group, but no in normal saline group. BBB hind limb motor function score of cell transplantation group was significantly improved compared with normal saline group improved (P < 0.01).CONCLUSION: Local injection of embryonic neural stem cells betters neuroelectrophysiology and motor function of hind limbs following high level SCI.