The Catalytic Mechanism and Activity Modulation of Manganese Superoxide Dismutase / 生物化学与生物物理进展

Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn2+SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn2+SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn2+SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn2+ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O2• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O2• into the inner sphere, and avoid O2•/Mn2+ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Pancreatic fistula after pancreaticoduodenectomy: Risk factors and preventive strategies

Purpose: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is a worrisome and life-threatening complication. This study aimed to investigate the risk factors and preventive strategies for POPF after PD. Materials and Methods: We retrospectively reviewed 301 consecutive patients who underwent PD at our hospitals between January 2011 and December 2017. We analyzed the pancreatic fistula rate according to the clinical characteristics, pathologic and laboratory findings, and the anastomotic methods and summarized the prevention measures. Results: Postoperative morbidities included pancreatic leakage in 10.30% (31/301), delayed gastric emptying in 22.92% (69/301), abdominal infection in 6.98% (21/301), post-PD hemorrhage in 4.65% (14/301), and bile leakage in 4.98% (15/301), and the mortality rate was 2.33% (7/301). POPF was the most prominent factor for preoperative morbidity. Significant risk factors for pancreatic fistula were a soft pancreas, small pancreatic duct, tumor location, and interrupted anastomosis. Of these, soft texture, pancreatic duct <4 mm, and end-to-end anastomosis through hand suture closure were independent risk factors on multivariate analysis, while interrupted anastomosis, internal stent, and somatostatin use were risk factors in the high-risk pancreas subgroup. Conclusions: Our study demonstrated that pancreatic fistula is related to a soft texture and small pancreatic duct. The surgeon must consider these risk factors when performing PD. Thus, we propose a risk- and indication-adapted choice of anastomosis or an individualized approach for the pancreatic remnant to reduce the pancreatic fistula rate

Comparison of image quality and radiation doses of double lower extremities full-length photography by two X-ray exposure modes / 医疗卫生装备

Objective To compare two exposure modes on image quality and radiation dose when used for double lower extremities full-length photography so as to provide guidance for clinical application. Methods Totally 60 patients undergoing double lower extremities full-length photography were selected with sequential experiment and then divided into two groups randomly and equally,of whom,there were four ones with genu varum.In the two groups,one group applied the exposure mode of AEC,and the other involved in FIXED mode.Then the two groups were compared on image quality and radiation dose. Results The exposure radiation to the patient under FIXED mode was higher than that under AEC mode although the common patients had the image quality with no significant difference in the two groups, and FIXED mode resulted in higher image quality for the patients with genu varum than AEC mode.Conclusion Exposure modes have effects on image quality and exposure dose,and it's suggested that AEC mode be applied for common patients from the aspect of radiation protection while FIXED mode be used for the patients with genu varum. [Chinese Medical Equipment Journal, 2018,39(5):68-70,74]

Effects of Acupuncture on Inflammation in Prefrontal Cortex of Vascular Dementia Rats / 中国中医药信息杂志

Objective To observe the effects of acupuncture on TLR4, inflammation factors IL-1β and IL-6 expressions in the prefrontal cortex of vascular dementia (VD) rats; To investigate the brain protective mechanisms of acupuncture. Methods A total of 50 rats were randomly divided into sham-operation group, model group, acupuncture group, and placebo-acupuncture group. The animal model of VD was replicated by permanent bilateral common carotid artery occlusion (2VO) in rats. Acupuncture was performed at three days after surgery, once daily for two weeks. Morris water maze was used to test the cognitive function. The expressions of Iba1 and TLR4 were assessed by immunohistochemical method. Inflammation factors IL-1β and IL-6 mRNA expressions were tested by RT-PCR. Results Compared with sham-operation group, the model group rats showed impaired spatial learning and memory ability, and expression of Iba1, TLR4, and IL-1β, IL-6 increased. Compared with the model group, the spatial learning and memory abilities of the acupuncture group were improved, and the expression of Iba1, TLR4 and IL-1β, IL-6 in the prefrontal cortex decreased. These effects were not found in the placebo-acupuncture group. Conclusion The effect of acupuncture may be achieved by inhibiting microglia activate, decreasing the expressions of TLR4, IL-1β and IL-6 in the prefrontal cortex, resulting in improving spatial learning and memory ability of VD rats.

Magnetic Resonance Gd-RGD Imaging Study of Hepatocellular Carcinoma with High and Low Metastatic Potential before and after Human Bone Marrow-derived Mesenchymal Stem Cell Intervention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Biotherapy based on human bone marrow-derived mesenchymal stem cells (BMSCs) is currently the focus of research, especially in the field of autologous stem cell transplantation. A novel type of metastasis-associated magnetic resonance (MR) molecular imaging probe was constructed, and the changes in metastasis and proliferation of hepatocellular carcinoma (HCC) before and after BMSC intervention were observed through MR imaging (MRI).</p><p><b>METHODS</b>Metastasis-associated MR molecular imaging probe, integrin αvβ3ligand cRGD-PEG-DGL-DTPA-Gd (Gd-RGD), were constructed. After human BMSC intervention was performed for 6 weeks, tumor weight inhibition rates were calculated, and the RGD molecular probe was imaged through MRI with molecular imaging agent Gd-DTPA as control. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the MRI experiment were used as semi-quantitative indicators. Polymerase chain reaction method was performed to detect proliferation- and metastasis-associated indicators, transforming growth factor β-1 (TGFβ1), osteopontin (OPN), and integrin subunit αvand β3.</p><p><b>RESULTS</b>The highest tumor weight inhibition rates were observed 3 weeks after the BMSC transplantation. The MR Gd-RGD in the HCC tissues after the BMSC intervention showed less enhancement than Gd-DTPA. The Gd-DTPA MRI of control group had higher SNR and CNR than Gd-RGD MRI in the experimental groups (P < 0.05). For high metastatic potential hepatocellular carcinoma (MHCC97-H), significant differences were observed in the SNRs and CNRs of Gd-RGD MRI before and after the BMSC intervention (P < 0.05). For low metastatic potential hepatocellular carcinoma (MHCC97-L), the CNRs of Gd-RGD MRI were statistically different before and after BMSC intervention (P < 0.05). With regard to MHCC97-H, OPN, β3, and TGFβ1 expression significantly decreased after BMSC intervention (P < 0.05). In MHCC97-L and OPN, β3, TGFβ1, and αv expression after BMSC intervention decreased, and the difference was statistically significant (P < 0.05).</p><p><b>CONCLUSIONS</b>The CNR index of MRI is a good indicator for distinguishing high- and low-metastatic potential HCC tissues. After BMSC transplantation of MRI through the two kinds of tracer, the SNR and CNR indexes can distinguish two kinds of high and low metastatic potential HCC tissues, and Gd-RGD imaging is more suitable in distinguishing the metastatic potential changes through BMSC intervention.</p>

Comparison of Positron Emission Tomography Using 2-18F-fluoro-2-deoxy-D-glucose and 3-deoxy-3-18F-fluorothymidine in Lung Cancer Imaging / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography (CT) imaging results remains a significant challenge. The 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[18F]-fluorothymidine (18F-FLT) in lung cancer PET/CT imaging.</p><p><b>METHODS</b>The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established (n = 12), and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values (SUVs), and Ki-67 proliferation marker expression were investigated.</p><p><b>RESULTS</b>The cell-tracer binding ratio for the A549 cells using the 18F-FDG was greater than the ratio using 18F-FLT (P < 0.05). The Ki-67 expression showed a significant positive correlation with the 18F-FLT binding ratio (r = 0.824, P< 0.01). The tumor-to-nontumor uptake ratio of 18F-FDG imaging in xenografts was higher than that of 18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of 18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of 18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of 18F-FDG and 18F-FLT (r = 0.658, P< 0.05 and r = 0.724, P< 0.01, respectively).</p><p><b>CONCLUSIONS</b>The 18F-FDG uptake ratio is higher than that of 18F-FLT in A549 cells at the cellular level. 18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.</p>

Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Quantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis.</p><p><b>METHODS</b>Twenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II.</p><p><b>RESULTS</b>The average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (P<0.001). T2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen.</p><p><b>CONCLUSION</b>This study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.</p>

Magnetic resonance urography and X-ray urography findings of congenital megaureter / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To observe the imaging findings of congenital megaureter in order to enhance the understanding of this disease.</p><p><b>METHODS</b>Image data of 5 patients with congenital megaureter and 2 misdiagnosed patients were analyzed, and image findings of congenital megaureter were summarized.Elscint Prestig 2.0T superconductive magnetic resonance urography (MRU) with conventional sequence (spin-echo, T1WI560 ms/16 ms; fast spin-echo, T2WI 9600 ms/96 ms ) was performed. Raw data were acquired with fastspin-echo sequence from heavy T2-weighted image (9600 ms/120 ms). Post-processing method of MRU was the maximum intensity projection with three-dimensional reconstruction in the workstation. Intravenous pyelography (IVP) was conducted, in which X-rayfilms were taken 7 minutes, 15 minutes, and 30 minutes after injecting contrast agent, exceptthat in 2 patients the films were taken delayed at 60 and 90 minutes .X-ray retrograde pyelography was performed on 2 patients, successful in one butfailed in the other.</p><p><b>RESULTS</b>The dilated ureter showed hypointensity on T1-weighted images and hyperintensity on T2-weighted images in conventional MRI. The mass wall was intact, uniform in thickness, and showing hypointensity on T1-weighted and T2-weighted images. The MRU images showed a retroperitoneal mass appearing as an elongated tubular cystic structure spreading from kidney to bladder. MRU also revealed dilated calices and renal pelvis, pelviureteric obstruction, and renal duplication. The main signs of congenital megaureter in X-urography was significant dilatation of ureter, or normal renal pelvis with ureter dilatation, hydronephrosis, deformity, and displacement.</p><p><b>CONCLUSIONS</b>MRU with X-urography could visualizethe characteristics of congenital megaureter, including the dilation of renal pelvis and ureter, calculi, urinary tract duplication, and stenosis location. The two techniques can complement each other in disease diagnosis and provide more detailed information for preoperative treatment.</p>

18F-FLT uptake in human colorectal cancer cells in relation to early response to radiation therapy:an in vitro study / 中华核医学杂志

Objective To evaluate whether 18F-fluorothymidine(FLT) can be used to monitor early response to irradiation in colorectal cancer (CRC).Methods SW480 cells were cultured and irradiated with 0, 10, and 20 Gy.Twenty-four hours later, morphological changes, apoptosis, necrosis, proliferation,and cell cycle phases were observed.Uptake of 18F-FLT was measured in these tumors in vitro from 24 h to 72 h after irradiation.The one-way analysis of variance was used to analyze the data.Results Apoptotic and necrotic cells were detected 24 h after radiotherapy.SW480 cells proliferation was significantly delayed after irradiation in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTI) assay.Cell cycle analysis showed that SW480 cells had a decreased fraction of cells in S phase( from 33.23% to 9.24%,then to 5.43% ) and an arrested fraction in G0-G1.After SW480 cells were cultured for60 min, the uptake of 18F-FLT was (5.21 ± 1.60) %; and 24 h after irradiation of 10 Gy, the uptake decreased significantly to (4.27±0.48)% (F=8.253, P=0.009).And 72 h after irradiation, the uptake further decreased significantly to (3.39 ± 0.59) % ( F = 36.715, P＜0.001 ).In tumor tissue, the uptake of 18F-FLT reduced significantly 72 h after radiotherapy (10 Gy:F = 12.388, P = 0.007; 20 Gy:F = 16.744, P = 0.004) and the attenuation degree increased with the radiation dose.Conclusion The uptake of 18F-FLT in SW480 cells or in CRC could reflect the changes of SW480 cells in proliferation, cell cycle re-distribution, cell apoptosis and necrosis.The results suggest that 18F-FLT may be used for monitoring early response to irradiation of CRC.

Prediction of metastatic tendency of human colorectal cancer using PET imaging in nude mice / 中华核医学杂志

Objective To evaluate the predictive value of 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine(FLT) PET in monitoring the metastatic potential of human colorectal cancer (CRC).Methods Human CRC cell lines SW480 and SW620 were cultured and implanted into nude mice to create CRC models. Tumor growth,metastatic status and survival were assessed in CRC bearing mice. Uptake of 18F-FDG and 18F-FLT in SW480 and SW620 cells was detected In vitro at 0,30,60,90,120 min after incubation. PET images of both tracers were acquired for SW480 and SW620 tumor-bearing mice using the small animal PET at 60 min after tracer injection. Region of interest (ROI) was drawn using Image J software on reconstructed PET images. Immunocytochemistry and Western blot analysis of the tumor tissue were performed. The correlation between tracer uptake and tumor marker expression was evaluated using linear regression. Results Compared with SW620 tumor-bearing mice,SW480 induced tumor grew much faster ( t = - 3.332,P = 0.004),the tumor-bearing mice had more serious dyscrasia ( t = 2.240,P = 0.038 ),shorter survival and higher metastatic rate. In vitro study,the uptake of both 18F-FDG and 18F-FLT in SW620 cells was lower than that in SW480 cells. 18F-FLT uptake was higher than 18F-FDG uptake in both SW480 and SW620 cells. After incubation for 60 min,the uptake of 18F-FDG in SW480 and SW620 cells was ( 1.76 ± 0.87 )% and ( 1.14 ± 0.38 )%,respectively ( t = - 2.507,P = 0.021 ); while the uptake of 18F-FLT in SW480 and SW620 cells was (5.21 ± 1.60)% and (2.90 ± 1.82)%,respectively (t =3.497,P =0.002). In micro-PET study,the 18F-FDG radioactivity ratio of tumor to non-tumor (T/NT) in SW480 and SW620 tumors was 2.69 ± 0.98 and 3.09 ± 1.26 respectively (t =0.657,P =0.524); while T/NT of 18F-FLT in SW480 and SW620 tumors was 3.65 ±0.51 and 2.22 ±0.42 (t =6.491,P ＜0.001 ),respectively. In immunocytochemistry and western blot assay,heat shock protein(HSP) 27,Integrin β3,vascular endothelial growth factor receptor 2 ( VEGFR2 ) and Ki67 were all over expressed in two kinds of tumor cells with different intensities. HSP27 and Integrin β3 expression was higher in SW480 cells than that in SW620 cells. While VEGFR and Ki67 expression was lower in SW480 cells than that in SW620 cells. The uptake of 18F-FLT closely correlated with the expression of HSP27 ( r =0.924,P =0.004) and Integrin β3 (r=0.813,P =0.025). 18F-FDG uptake inversely correlated with the survival of tumor-bearing mice (r =0.500,P=0.017). Conclusions The uptake of 18F-FDGand 18F-FLT may reflect different biological characteritics of CRC. High 18F-FLT uptake in CRC on PET scan may predict high metastatic tendency.

Pitfalls in positron emission tomography/computed tomography imaging: causes and their classifications / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To describe the pitfalls in positron emission tomography/computed tomography (PET/CT) imaging and classify them according to the principles of their generation.</p><p><b>METHODS</b>We summarized retrospectively the 18F-fluorodeoxyglucose (FDP) PET/CT imaging pitfalls through reviewing the PET/CT images of 872 patients. The pitfalls were divided into artifacts and infrequent physiological uptake, and the artifacts were further classified according to their causes. Meanwhile, we calculated the incidences of various pitfalls. Whether the PET/CT pitfalls influenced the diagnostic decision was analyzed. The appearances of pitfalls in PET were also described.</p><p><b>RESULTS</b>Pitfalls could be found in PET/CT images of 684 (78.4%) patients. Artifacts were found in 664 (76.15%) patients, and could be classified into self-factor artifacts and equipment- or technology-related artifacts. Among self-factor artifacts, respiratory motion (57.5%), postprandial or hyperglycemia artifacts (2.41%), and metal or high density matter artifacts (1.38%) were frequent. As for equipment- or technology-related factors, injection point outleakage or radiotracer contamination (13.88%) and truncation artifacts (1.83%) were most common ones. Infrequent physiological FDG uptakes, including fatty uptake, endometrial uptake, and bilateral breast feeding period uptake, were found in 20 (2.29%) patients. Among all pitfalls, the artifacts in 92 (13.4%) patients and infrequent physiological uptakes in 6 (0.88%) patients affected the diagnostic results. Artifact images in PET could be described as hot or cold area and the images of infrequent physiological uptake were always shown as hot area.</p><p><b>CONCLUSIONS</b>The incidence of pitfall in PET/CT imaging was high and the causes of pitfalls are various. Among all causes that artifacts generated, respiratory motion is the most common. Some pitfalls may disturb clinical physicians' decision, so it is important to recognize artifacts and physiological uptake, and distinguish them from pathological uptakes.</p>