The protective effect and mechanism of constant mild hypothermia on swine kidney after cardiac arrest and extracorporeal ardiopulmonary resuscitation / 医学研究生学报

Objective To evaluate the protective effect and mechanism of mild hypothermia on swine kidney after cardiopulmonary resuscitation, and whether changes in body temperature during mild hypothermia weaken the protective effect of mild hypothermia. Methods 18 swines were randomly divided into constant mild hypothermia group (CMH), variable mild hypothermia group (VMH) and control group (CON), with 6 swines in each group. Cardiac arrest model was successfully made. Then ECPR and temperature management was adopted. The target body temperature was 34℃ in the CMH group, and 37℃ in the control group, while the target body temperature of the VMH group fluctuated from 33 to 35 ℃ every two hours. After 24h, the animals were slowly reheated and then sacrificed. The kidneys were taken for real-time quantitative PCR, immunohistochemistry and histopathological examination. Results The expression levels of Bax, GRP78 and CHOP in the CMH group were lower than those in the CON group. Moreover, the expression of GRP78 in the CMH group were lower than those in the VMH group. The expression of Bcl-2 in the CMH group were higher than those in the VMH group and the CON group, and the expression of Bcl-2 in the VMH group were higher than those in the CON group (all P < 0.05). The positive expression of Bax was the most significant in the CON group and the least in the CMH group. The positive expression of Bcl-2 was the most significant in the CMH group and the least in the CON group. The nuclear membrane of porcine kidney cells shrank, nucleoli shrank and mitochondria swelled obviously in the CON group. The morphological injury changes were mild in the CMH group compared with the VMH group, while the CON group showed the severest change. Conclusion Mild hypothermia could attenuate the renal tubular cells apoptosis after cardiopulmonary resuscitation by inhibiting endoplasmic reticulum stress pathway, thus playing a protective role to the kidney. While aAbnormal temperature fluctuation during mild hypothermia maintenance may weaken the protection of kidney by mild hypothermia.

Association between HLA-DR Expression and Multidrug-resistant Infection in Patients with Severe Acute Pancreatitis / 华中科技大学学报（医学）（英德文版）

Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

Association between HLA-DR Expression and Multidrug-resistant Infection in Patients with Severe Acute Pancreatitis / 华中科技大学学报（医学）（英德文版）

Multidrug-resistant (MDR) bacterial infection is a common complication of severe acute pancreatitis (SAP).This study aimed to explore the association between human leukocyte antigen-antigen D-related (HLA-DR) expression and multidrug-resistant infection in patients with SAP.A total of 24 SAP patients who were admitted to Nanjing Drum Tower Hospital between May 2015 and December 2016 were enrolled in the study.The percentages of CD4+,CD8+,natural killer (NK),and HLA-DR (CD14+) cells and the CD4+/CD8+ cell ratio on days 1,7,14,and 28 after admission were determined by flow cytometry.Eighteen patients presented with the symptoms of infection.Among them,55.6％ patients (10/18) developed MDR infection.The most common causative MDR organisms were Enterobacter cloacae and Acinetobacter baumannii.The CD4+/CD8+ cell ratio and the percentage of NK cells were similar between patients with non-MDR and patients with MDR infections.In patients without infection,the HLA-DR percentage was maintained at a high level throughout the 28 days.Compared to the patients without any infection,the HLA-DR percentage in patients with non-MDR infection was reduced on day 1 but increased and reached similar levels on day 28.In patients with MDR infection,the HLA-DR percentage remained below normal levels at all-time points.It was concluded that persistent down-regulation of HLA-DR expression is associated with MDR bacterial infection in patients with SAP.

Histopathological classification and location of consecutively operated meningiomas at a single institution in China from 2001 to 2010 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Meningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010.</p><p><b>METHODS</b>This study investigated the demographic background of 7084 meningioma cases, and the subtypes and locations of the tumors. Sex and age distributions were analyzed, and the pathological subtypes were classified according to the World Health Organization (WHO) classification. The location of the meningiomas was also categorized.</p><p><b>RESULTS</b>The female:male ratio of the 7084 cases was 2.34:1. The mean age was 51.4 years (range, 11 months-86 years). The mean age of cases of WHO grade I meningioma was significantly older than that of grade II or III meningiomas (P < 0.001, Fisher's Least Significant Digit test). There was a significantly higher female:male ratio in WHO grade I meningiomas than in grade II or grade III meningiomas (2.57, 1.03 and 0.76, respectively; P < 0.001, χ(2) test). Meningothelial (n = 2061) and fibrous meningiomas (n = 3556) were the most common subtypes, comprising 79.3% of all meningiomas. All meningioma cases were classified into 23 locations in this study, with the cerebral convexity the most common site (38.33%, n = 2722). Cases with uncommon locations such as extra-cranial and sylvian fissure meningiomas were also present in this series.</p><p><b>CONCLUSIONS</b>Female predominance was found for benign meningiomas, while malignant subtypes showed male predominance. The mean age of patients with WHO grade I meningiomas was older than that of patients with higher-grade tumors. Meningothelial and fibrous meningiomas were the most common subtypes. The cerebral convexity was the most common meningioma location.</p>

Preoperative surgical planning for intracranial meningioma resection by virtual reality / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The Dextroscope system by Volume Interactions (Singapore) had been applied to minimally invasive neurosurgery in many units. This system enables the neurosurgeon to interact intuitively with the three-dimensional graphics in a direct manner resembling the way one communicates with the real objects. In the paper, we explored its values in pre-operation surgical planning for intracranial meningiomas resection.</p><p><b>METHODS</b>Brain computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance venography (MRV) were performed on 10 patients with parasagittal and falcine meningiomas located on central groove area; brain CT, MRI and magnetic resonance angiography (MRA) were performed on 10 patients with anterior skull base meningiomas and 10 patients with sphenoid ridge meningiomas. All these data were transferred to Dextroscope virtual reality system, and reconstructed. Then meningiomas, skull base, brain tissue, drainage vein and cerebral arteries were displayed within the system, and their anatomic relationships were evaluated. Also, the simulation operations were performed.</p><p><b>RESULTS</b>For parasagittal and falcine meningiomas, the relationships of tumor with drainage vein and superior sagittal sinus were clearly displayed in the Dextroscope system. For anterior skull base and sphenoid ridge meningiomas, the relationships of tumor with bilateral internal carotid arteries, anterior cerebral arteries, middle cerebral arteries and skull base were vividly displayed within the virtual reality system. Surgical planning and simulation operation of all cases were performed as well. The real operations of all patients were conducted according to the simulation with well outcomes.</p><p><b>CONCLUSIONS</b>According to the virtual reality planning, neurosurgeons could get more anatomic information about meningioma and its surrounding structures, especially important vessels, and choose the best approach for tumor resection, which would lead to better prognosis for patients.</p>

Increased expression of osteopontin in brain arteriovenous malformations / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The precise mechanisms responsible for the development and growth of intracranial arteriovenous malformations (AVMs) remain unclear. Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions. This study aimed to analyze the expression of OPN in human brain AVMs.</p><p><b>METHODS</b>The AVM nidus was surgically obtained from patients with AVM, whereas control brain artery specimens were surgically obtained from patients with epilepsy. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of OPN mRNA in biopsy specimens. OPN protein expression was localized by immunohistochemistry. The statistical differences between different groups were assessed by two-way analysis of variance (ANOVA).</p><p><b>RESULTS</b>We analyzed 36 brain AVM specimens and 8 control brain artery specimens. Eleven patients with brain AVM received embolization treatment, and five underwent gamma knife radiotherapy before resection. Nineteen patients with brain AVM had a history of hemorrhage from AVMs. The expression of OPN mRNA was significantly higher in AVMs than that in the control specimens (25.76 ± 2.71 vs. 21.46 ± 2.01, P < 0.01). There was no statistically significant difference in the extent of OPN mRNA expression between the AVM group with and that without history of hemorrhage (26.13 ± 2.45 vs. 25.34 ± 2.99) or gamma knife radiotherapy (24.39 ± 2.10 vs. 24.53 ± 1.85). However, the difference between the AVM group with and that without embolization treatment history was statistically significant (24.39 ± 2.10 vs. 28.80 ± 1.13, P < 0.01). In the group with gamma knife radiotherapy history, OPN expression was found in arteries with early-stage radio-effect.</p><p><b>CONCLUSIONS</b>OPN may contribute to the vascular instability of brain AVMs. It may play an important role in the pathophysiological process related to embolization treatment.</p>

Diagnostic value of contrast-enhanced intraoperative Doppler sonography for cerebral arteriovenous malformations compared with angiography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intraoperative Doppler sonography has been used in the neurosurgical operating room for the localization and description of cerebral arteriovenous malformations (AVMs). This study aimed to investigate the clinical value of contrast-enhanced intraoperative Doppler sonography, including its ability to assess the location and identify of feeding arteries in patients with AVMs and to compare this method with angiography.</p><p><b>METHODS</b>Twenty-three patients with cerebral AVMs who were diagnosed using angiography, were examined with contrast-enhanced intraoperative Doppler sonography. As an echo-enhancing agent, Sulphur Hexafluoride Microbubbles for Injection ("SonoVue") was administered intravenously in all patients. Sonogram results were reviewed and correlated with angiographic findings. For statistical analysis, the Wilcoxon signed-rank test was applied.</p><p><b>RESULTS</b>Angiography identified 20 AVM lesions in the anterior or middle fossa and 3 in the posterior fossa. Contrast-enhanced intraoperative Doppler was somewhat less sensitive for only detecting 21/23 (91.3%) of the AVM lesions. Additionally, contrast-enhanced intraoperative Doppler slightly underestimated AVM size compared with angiographic findings but showed feeding arteries with sufficient acoustic properties. In 15 patients, angiography revealed a coincidental blood supply from another intracranial vessel, which was missed by contrast-enhanced intraoperative Doppler sonography.</p><p><b>CONCLUSIONS</b>In a limited group of patients with AVMs, contrast-enhanced intraoperative Doppler sonography was a less sensitive but useful and simple method for the detection of AVMs in contrast to angiography. No specific untoward effects were attributed to the use of "SonoVue" as a contrast-enhancing substance.</p>

Long-term stable expression of antisense cDNA of cyclin B1 profoundly inhibits the proliferation of tumor cells and suppresses tumorigenicity in implanted mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cyclin B1 (CLB1) is necessary for mitotic initiation in mammalian cells and plays important roles in cancer development. Therefore, a potential strategy in cancer therapy is to suppress the activity of CLB1 by delivering antisense constructs of CLB1 into tumor cells. In previous CLB1 studies, antisense constructs with a short half life were often used and these constructs might not persistently inhibit CLB1.</p><p><b>METHODS</b>We successfully created a recombinant plasmid encoding the full-length antisense cDNA of mouse cyclin B1 (AS-mCLB1) and transfected this construct to the murine Lewis lung carcinoma (LL/2) and CT-26 colon carcinoma (CT-26) cells. We isolated clones of LL/2 and CT-26 transfectants with stable expression of AS-mCLB1. Reverse transcriptional polymerase chain reaction (RT-PCR) and Western blot were applied to detect the expression of the mRNA and protein levels of CLB1. To further test the efficacy of this strategy in vivo, AS-mCLB1-expressing LL/2 and CT-26 transfectants were implanted into mice.</p><p><b>RESULTS</b>We found the expression of the mRNA and protein levels of CLB1 decrease in these transfectants. The inhibition of CLB1 caused prominent G1 arrest, abnormal morphology, retarded cell growth and an increase in apoptosis. In AS-mCLB1-expressing LL/2 and CT-26 transfectants implanted mice, tumorigenicity was effectively suppressed compared with the controls. In addition, the expression of AS-mCLB1 also significantly increases the survival duration of implanted animals.</p><p><b>CONCLUSION</b>AS-mCLB1 is likely to be useful in future cancer therapy, which may be associated with its ability to down-regulate the expression of CLB1 and then induce G1arrest and apoptosis in tumor cells.</p>

Clinical experience of 70 cases of cerebral arteriovenous malformations embolization with Onyx, a novel liquid embolic agent / 中华外科杂志

<p><b>OBJECTIVE</b>To report our clinical experience of using Onyx, a new liquid embolic agent, to treat cerebral arteriovenous malformations (AVMs) as well as its efficacy.</p><p><b>METHODS</b>Seventy cases were placed with 6F sheath in the femoral artery after Seldinger puncture and 6F guiding catheter was introduced into the internal carotid artery or vertebral artery, then a microcatheter was navigated into the nidus of AVMs. Slow injection of Onyx under fluoroscopic control was performed to embolize cerebral AVMs using the "plug and push" technique.</p><p><b>RESULTS</b>Thirteen AVM cases (18.6%) were totally occluded by Onyx and 5 cases of which didn't recurrence at 6-month after operation. Thirty-eight cases (54.3%) were subtotally occluded, while another 19 cases (27.1%) were partially embolized. Severe cerebral hemorrhage occurred in 4 cases, 2 of which had mild to severe hemiplegia after operation, and one died. Mild hemiplegia was also found in 1 case due to functional area embolization, and visual field deficit in 2 cases.</p><p><b>CONCLUSIONS</b>Onyx has unique and distinctive superiority in treating cerebral AVMs. Nonetheless, the correct embolization technique should be learned to achieve good clinical results and avoid complications.</p>

Risk factors for intracranial aneurysm in a Chinese ethnic population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Intracranial aneurysm (IAN) is a protruding bubble or a sac on a brain artery that balloons out over time, which may lead to spontaneous subarachnoid hemorrhage (SAH), ultimately disability and mortality. Current research indicates that the disease is due to multiple causes, including environmental factors and various congenital abnormalities of blood vessels. Apart from congenital predisposition, various high-risk factors such as sex, age, hypertension, and atherosclerosis are involved in the formation of intracranial aneurysms. The aim of this study was to investigate the risk factors associated with the formation of sporadic intracranial aneurysms in Chinese Han ethnic patients.</p><p><b>METHODS</b>A total of 251 patients with intracranial aneurysm and 338 patients with other cerebral diseases (control group) were enrolled in this study. Single factor and logistic regression model were used to analyze the association of intracranial aneurysms with age; sex; cigarette smoking; alcohol or cocaine consumption; history of hypertension, coronary artery disease, diabetes mellitus and inherited connective tissue disease; and the levels of fasting blood glucose and blood fat. The data expressed as mean +/- standard deviation were processed with the statistical software SPSS13. Quantitative and qualitative data were analyzed by the independent-sample t test, and the chi-square test respectively. Logistic regression method was used to analyze the multiple factors.</p><p><b>RESULTS</b>In the 251 patients, 163 (64.94%) were at age of 40 to 60 years. Sex (OR, 1.41; 95% CI, 1.01 - 1.96), cigarette smoking (OR, 1.81; 95% CI, 1.06 - 3.10), hypertension (OR, 2.32; 95% CI, 1.30 - 4.16) and fasting blood glucose were significantly associated with intracranial aneurysm (P < 0.05). Intracranial aneurysm was correlated with alcohol consumption, coronary artery disease, and the level of blood lipids (P > 0.05). Using logistic regression analysis, we identified female sex and advanced age as significant risk factors for sporadic intracranial aneurysms.</p><p><b>CONCLUSIONS</b>Sporadic intracranial aneurysms mostly occur in people aged 40 to 60 years. Feminine, cigarette smoking, and hypertension are independent risk factors for the disease, and the gender is the most significant factor. Advanced age can increase the effect of these risk factors.</p>

Inflammatory reaction after focal cerebral ischemia in mouse / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In response to the inflammatory reaction, circulating leukocytes aggregate and adhere to the endothelial cells and eventually pervade into tissues, resulting in cell damage. This study was to detect the inflammatory reactions in mouse focal cerebral ischemia and their distinct characteristics in the ischemic basal ganglia and surrounding cortex.</p><p><b>METHODS</b>Mice were subjected to permanent occlusion of the left middle cerebral artery (MCAO) by introducing a suture for 2 to 120 hours. The expression of intercellular adhesion molecule 1 (ICAM-1) and Mac-1 was determined immunohistochemically. The myeloperoxidase (MPO) activity of the ischemic regions was measured.</p><p><b>RESULTS</b>Four hours after MCAO, the number of ICAM-1 positive vessels in the ischemic basal ganglia increased (9.2 +/- 2.8 per mm(2)), peaked at 48 hours (29.6 +/- 4.8 per mm(2)), and decreased after 72 hours. In the ischemic cortex, the number increased rapidly 4 hours after MCAO (19.4 +/- 6.1 per mm(2)), peaked at 48 hours (44.4 +/- 16.8 per mm(2)), and declined after 72 hours. Mac-1 positive cells were seen in the ischemic basal ganglia (3.4 +/- 1.2 per mm(2)) 12 hours after MCAO, peaked after 48 hours (20.2 +/- 6.3 per mm(2)), and decreased after 72 hours. In the ischemic cortex, however, the number increased 4 hours after MCAO (4.3 +/- 1.7 per mm(2)), peaked after 48 hours (20.9 +/- 8.4 per mm(2)), and remained high at 120 hours. The MPO activity increased in the ischemic basal ganglia 12 hours after MCAO (0.111 +/- 0.023 U/g), peaked after 24 hours (0.194 +/- 0.059 U/g), and decreased after 72 hours. In the ischemic cortex, the MPO activity increased 12 hours after MCAO (0.110 +/- 0.032 U/g), peaked after 24 hours (0.210 +/- 0.067 U/g), and remained elevated at 120 hours.</p><p><b>CONCLUSIONS</b>The increased expression of ICAM-1 in the ischemic brain of mouse in the early phase of MCAO followed by the over-expression of Mac-1 and the increased MPO activity suggests that focal ischemia leads to early onset of inflammation. The inflammatory response is more persistent and intensive in the ischemic cortex than in the ischemic basal ganglia.</p>

New mutations of the 12th exon of CCM1 gene in Chinese patients with intracranial cavernous angiomas / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the effect of CCM1 gene mutations in Chinese patients with intracranial cavernous angiomas(ICCA).</p><p><b>METHODS</b>Twenty-one ICCA patients confirmed by pathology after operations in hospital from June 2002 to Feb.2003 and 15 healthy individuals as contrast were recruited. The peripheral venous blood samples of all the individuals were collected, and then DNA was extracted from the blood samples followed by amplification of exon 12 and some of its intron sequence using PCR. After purification, the PCR products were directly sequenced by ABI PRISM377 sequencing instrument.</p><p><b>RESULTS</b>Three mutations of CCM1 gene were found in 5 patients and reported firstly. There existed a missense mutation of 1172C-->T in exon 12 in 5 patients, which led the No.391 amino acid of KRIT1 protein, serine, to phenyalanine. There existed a missense mutation of 1160A-->C in one patient, which led the No.387 amino acid, glutamine, to proline. Another mutation was an intronic mutation of IVS12-4C-->T in 4 patients. In contrast no mutations were found.</p><p><b>CONCLUSION</b>The authors firstly report that mutations of CCM1 gene in exon 12 also exist in Chinese ICCA patients and those mutations are related with the occurring of ICCA.</p>

U0126 prevents ERK pathway phosphorylation and interleukin-1beta mRNA production after cerebral ischemia / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the role of extracellular signal-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) on ischemic brain.</p><p><b>METHODS</b>Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 (pERK1/2), phosphorylated mitogen activated protein kinase kinase (pMEK), and phosphorylated Elk-1 (pElk-1) was assessed by Western blot analysis and immunohistochemistry. Interleukin (IL)-1beta mRNA level was measured by ribonuclease protection assay.</p><p><b>RESULTS</b>Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1beta mRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1 to 4 hours after MCAO.</p><p><b>CONCLUSION</b>Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1beta mRNA via the inhibition of ERK pathway.</p>