Recent Advances in Biosensors for Nucleic Acid and Exosome Detection / 전남의대학술지

Biosensors are analytical devices for biomolecule detection that compromise three essential components: recognition moiety, transducer, and signal processor. The sensor converts biomolecule recognition to detectable signals, which has been applied in diverse fields such as clinical monitoring, in vitro diagnostics, food industry etc. Based on signal transduction mechanisms, biosensors can be categorized into three major types: optical biosensors, electrochemical biosensors, and mass-based biosensors. Recently, the need for faster, more sensitive detection of biomolecules has compeled researchers to develop various sensing techniques. In this review, the basic structure and sensing principles of biosensors are introduced. Additionally, the review discusses multiple recent works about nucleic acid and exosome sensing.

Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center, Randomized, Parallel, Open-label, Phase II Clinical Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.</p><p><b>METHODS</b>A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS).</p><p><b>RESULTS</b>The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively.</p><p><b>CONCLUSIONS</b>Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.</p>

Acute paraplegia following embolization of spinal dural arteriovenous fistula / 中华医学杂志(英文版)

Embolization therapy has been used as the initial treatment for spinal dural arteriovenous fistula (SDAVF) only for certain patients or in certain medical institutions due to its minimal invasiveness, but the recurrence of embolization remains a clinical challenge. The recurrent patient usually exhibits a gradual onset of symptoms and progressive deterioration of neurological function. Developing paraplegia several hours after embolization is commonly seen in patients with venous thrombosis-related complications, for which anticoagulation therapy is often administered. This article reports on a SDAVF patient who had weakness of both lower extremities before embolization and developed complete paraplegia several hours after embolization therapy, later confirmed by angiography as fistula recurrence. The symptoms were relieved gradually after second embolization. The pathophysiology of this patient is also discussed.

Experience of resection large clinoidal meningiomas / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical applied anatomy in the region of anterior clinoid process, and to improve the therapeutic efficacy of clinoidal tumors.</p><p><b>METHODS</b>Twelve patients with large meningiomas located in clinoid were surgically treated via the extended anterior and middle fossa combined with epidural approach between January 1998 and August 2004. The surgical outcome and follow-up results were reviewed retrospectively. Supraorbital-posterional approach and cranioorbital zygomatic approach were used when tumors involved cavernous sinus. Anterior clinoid process was grinded with high-speed drilling. Supply of tumors were blocked extradurally. Tumors were resected intradurally.</p><p><b>RESULTS</b>Of the 12 cases in large meningiomas located in clinoid, 8 cases had total removal of tumors, 3 patients had subtotal removal. Of the 10 patients with pre-operative severe visual deterioration, 6 patients was markedly improved, one patient unchanged and one patient worsened post-operatively. No death was found in this group.</p><p><b>CONCLUSIONS</b>Using epidural approach for clinoidal meningiomas and grinding anterior clinoid process was advantageous to block tumors base blood supply and detach infraclinoidal tumors from internal carotid artery. Supraorbital-pterional approach could minimize brain retraction and was advantageous to expose superior pole of giant tumors.</p>

Hemiparesis in carotid cavernous fistulas (CCFs): a case report and review of the literature / 中华创伤杂志(英文版)

Carotid-cavernous fistulas (CCFs) are abnormal arteriovenous anastamoses between the carotid artery and the cavernous sinus. These fistulas may be classified by cause (spontaneous or traumatic), flow velocity (high or low), or pathogenesis (direct or indirect). The most commonly adopted classification is that described by Barrow based on arterial supply. Traumatic CCFs are almost always direct shunts between the internal carotid artery (ICA) and the cavernous sinus. General features of CCFs, which may be apparent with any lesion, including bruit, headache, loss of vision, altered mental status and neurological deficits. Some fistulae may present primarily with hemorrhage before any evaluation can be performed. However, hemiparesis has been rarely observed. Only a literature review of Murata et al reported a case of hemiparesis caused by posttraumatic CCF, in which the fistula resulted in venous hypertension and subsequent brainstem congestion. While in our case, cerebral infarction was caused by total steal of the blood flow. The patient recovered after occlusion of the fistula with a detachable balloon.

Effects of magnesium sulfate on traumatic brain edema in rats / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of magnesium sulfate on traumatic brain edema and explore its possible mechanism.</p><p><b>METHODS</b>Forty-eight Sprague-Dawley (SD) rats were randomly divided into three groups: Control, Trauma and Treatment groups. In Treatment group, magnesium sulfate was intraperitoneally administered immediately after the induction of brain trauma. At 24 h after trauma, total tissue water content and Na(+), K(+), Ca(2+), Mg(2+) contents were measured. Permeability of blood-brain barrier (BBB) was assessed quantitatively by Evans Blue (EB) dye technique. The pathological changes were also studied.</p><p><b>RESULTS</b>Water, Na(+), Ca(2+) and EB contents in Treatment group were significantly lower than those in Trauma group (P<0.05). Results of light microscopy and electron microscopy confirmed that magnesium sulfate can attenuate traumatic brain injury and relieve BBB injury.</p><p><b>CONCLUSIONS</b>Treatment with MgSO4 in the early stage can attenuate traumatic brain edema and prevent BBB injury.</p>

Effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To observe the effects of ganglioside GM1 on reduction of brain edema and amelioration of cerebral metabolism after traumatic brain injury (TBI).</p><p><b>METHODS</b>An acute experimental closed TBI model in rats was induced by a fluid-percussion brain injury model. At five and sixty minutes after TBI, the animals were intraperitoneally injected by ganglioside GM1 (30 mg/kg) or the same volume of saline. At the 6th hour after TBI, effects of ganglioside GM1 or saline on changes of mean arterial pressure (MAP), contents of water, lactic acid (LA) and lipid peroxidation (LPO) in the injured cerebral tissues were observed.</p><p><b>RESULTS</b>After TBI, MAP decreased and contents of water, LA and LPO increased in brain injury group; however, MAP was back to normal levels and contents of water, LA and LPO decreased in ganglioside GM1 treated group, compared with those in brain injury group (P < 0.05). No significant difference between the saline treated group and the brain injury group (P > 0.05) was observed.</p><p><b>CONCLUSIONS</b>Ganglioside GM1 does have obvious neuroprotective effect on early TBI.</p>

The correlation between mRNA and protein expression of bax and bcl-xL follo wing fluid percussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alterations of bcl-2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis follow ing traumatic brain injury (TBI). Methods: Male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury(FPBI) of moderate severity. bax and bcl-xL mRNA and protein expression was detected by RT-PCR an d immunohistochemistry. In addition to morphological evidence of apoptosis, TUNE L histochemistry was used to identify DNA fragmentation in situ under both l ight and electron microscope, whereas characteristic internucleosomal DN A fragm entation of apoptosis was demonstrated by DNA gel electrophoresis. Resul ts: bcl-xL mRNA and protein decreased in the ipsilateral hemisphere t o the impact site as early as 6 h post-injury［(67.42±7.54)% and (85.85±5.72)% r espectively］. The decrease in bcl-xL mRNA and protein preceded apoptosis was observed 12 h post-injury. And this was the main cause of up-regulation of the ratio of bax to bcl-xL in the acute period(minutes-hours) followin g FPBI. bax mRNA and protein were observed to rise slowly, doubled 3 d post- injury, returned to sham level slowly. The delayed cell death (days-weeks) migh t associated with the up-regulation of pro-apoptotic gene bax. Conclusio n: The expression of bcl-xL and bax coincide with apoptosis following TBI. The reg ulation of bax and bcl-xL by TBI occur before transcription. The balance of bax/bcl-xL ratio determines the neurocytes to survive or die following FPBI.

Alteration of Bcl-2, Bcl-x and Bax protein expression following fluid per cussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alteration of bcl- 2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis following traumatic brain injury. Methods: Male Sprague -Dawley rats were subjected to lateral fluid percussion brain injury(FPI) of mo derate severity. Bcl-2, Bcl-x and Bax protein expression was detected by immun ohistochemistry. Results: (1) The immunoreactivity of Bcl-2 and Bcl-x protein decreased in the hippocampus ipsilateral impact site as early as 6 h post-injury, and this was the main cause of down-regulation of the ratio of Bcl-2+Bcl-x to Bax. (2) During 1-3 d after injury, the Bax protein express i on increased significantly, while the Bcl-2 and Bcl-x protein expression decre ased relatively slow. The decreased ratio of Bcl-2+Bcl-x to Bax was mainly due to the Bax up-regulation. Conclusion: The bcl-2 gene family is involved in neuronal apoptosis after FBI, and the protein expression alteration of the family members leads the neuronal cell to apoptosis.

The correlation between mRNA and protein expression of bax and bcl-xL follo wing fluid percussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alterations of bcl-2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis follow ing traumatic brain injury (TBI). Methods: Male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury(FPBI) of moderate severity. bax and bcl-xL mRNA and protein expression was detected by RT-PCR an d immunohistochemistry. In addition to morphological evidence of apoptosis, TUNE L histochemistry was used to identify DNA fragmentation in situ under both l ight and electron microscope, whereas characteristic internucleosomal DN A fragm entation of apoptosis was demonstrated by DNA gel electrophoresis. Resul ts: bcl-xL mRNA and protein decreased in the ipsilateral hemisphere t o the impact site as early as 6 h post-injury［(67.42±7.54)% and (85.85±5.72)% r espectively］. The decrease in bcl-xL mRNA and protein preceded apoptosis was observed 12 h post-injury. And this was the main cause of up-regulation of the ratio of bax to bcl-xL in the acute period(minutes-hours) followin g FPBI. bax mRNA and protein were observed to rise slowly, doubled 3 d post- injury, returned to sham level slowly. The delayed cell death (days-weeks) migh t associated with the up-regulation of pro-apoptotic gene bax. Conclusio n: The expression of bcl-xL and bax coincide with apoptosis following TBI. The reg ulation of bax and bcl-xL by TBI occur before transcription. The balance of bax/bcl-xL ratio determines the neurocytes to survive or die following FPBI.

Alteration of Bcl-2, Bcl-x and Bax protein expression following fluid per cussion brain injury in rats / 第二军医大学学报

Objective: To investigate the alteration of bcl- 2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis following traumatic brain injury. Methods: Male Sprague -Dawley rats were subjected to lateral fluid percussion brain injury(FPI) of mo derate severity. Bcl-2, Bcl-x and Bax protein expression was detected by immun ohistochemistry. Results: (1) The immunoreactivity of Bcl-2 and Bcl-x protein decreased in the hippocampus ipsilateral impact site as early as 6 h post-injury, and this was the main cause of down-regulation of the ratio of Bcl-2+Bcl-x to Bax. (2) During 1-3 d after injury, the Bax protein express i on increased significantly, while the Bcl-2 and Bcl-x protein expression decre ased relatively slow. The decreased ratio of Bcl-2+Bcl-x to Bax was mainly due to the Bax up-regulation. Conclusion: The bcl-2 gene family is involved in neuronal apoptosis after FBI, and the protein expression alteration of the family members leads the neuronal cell to apoptosis.

Study on metastasis-associated gene in carcinoma by cDNA microarray / 第二军医大学学报

Objective:To understand the molecular pat hophysiology of hepatocellular carcinoma and pancreatic cancer.Methods: We studied novel gene expression by cDNA microarray method. The PCR pro ducts of 4 096 genes and 12 800 gene were spotted onto a kind of chemical-mater ial-coated-glass slide in array. Both the mRNAs from 5 cases of hepatocellular carcinoma and 3 cases of pancreatic cancer were reversely transcribed to cDNAs with the incorporation of fluorescent-labeled dUTP to prepare the hybridization probes. After hybridization, BioDoor4096 and BioDoor12800 cDNA microarray were scanned for the fluorescent intensity. Tumor invasion-related gene expression w as screened through the analysis of difference in gene expression profile.Results:Among 4 096 and 12 800 target genes, there were 15 genes who se expression level differed from normal and carcinoma tissues. Therefore, they might be associated with metastasis.Conclusion:Further analysis of these differentially expressed metastasis-associated genes will be helpful for understanding the molecular mechanism of malignant carcinoma.

Study on metastasis-associated gene in carcinoma by cDNA microarray / 第二军医大学学报

Objective:To understand the molecular pat hophysiology of hepatocellular carcinoma and pancreatic cancer.Methods: We studied novel gene expression by cDNA microarray method. The PCR pro ducts of 4 096 genes and 12 800 gene were spotted onto a kind of chemical-mater ial-coated-glass slide in array. Both the mRNAs from 5 cases of hepatocellular carcinoma and 3 cases of pancreatic cancer were reversely transcribed to cDNAs with the incorporation of fluorescent-labeled dUTP to prepare the hybridization probes. After hybridization, BioDoor4096 and BioDoor12800 cDNA microarray were scanned for the fluorescent intensity. Tumor invasion-related gene expression w as screened through the analysis of difference in gene expression profile.Results:Among 4 096 and 12 800 target genes, there were 15 genes who se expression level differed from normal and carcinoma tissues. Therefore, they might be associated with metastasis.Conclusion:Further analysis of these differentially expressed metastasis-associated genes will be helpful for understanding the molecular mechanism of malignant carcinoma.