Pathological Observation of Blood Stasis Syndrome in Non-diabetic Peripheral Neuropathies: A Retrospective Analysis Based on Nerve Biopsy / 中国结合医学杂志

OBJECTIVE@#To investigate the pathological features of blood stasis syndrome (BSS) in non-diabetic peripheral neuropathy.@*METHODS@#Clinical data of 31 patients with non-diabetic peripheral neuropathy who had undergone nerve biopsy during December 2004 and December 2010 in Xuanwu Hospital Capital Medical University were retrospectively analyzed. According to Chinese medicine (CM) syndrome differentiation and signs, 26 patients were blood stasis type and 5 patients were non-blood stasis type. Clinical and pathological data were compared in detail.@*RESULTS@#Clinically, although both groups shared similar symptoms of limb numbness, weakness and sensory disturbances, the prevalence of neuralgia was much grievous in BSS group (73.1%, 26/31) compared with the non-BSS group (0%, 0/5). As for signs, dermal nutrients disturbance (84.6%, 22/26), dark or purple tongue (100.0%, 26/26), and sublingual varices (80.7%, 21/26) were more common in the BSS group than the non-BSS group (0%, 60%, 20%, respectively). The prevalence of qi deficiency cases (19/26) in the BSS group was significantly higher compared with the non-BSS group (1/5). The unique histological manifestations of BSS were axonal degeneration (16/26 vs 2/5 in non-BSS group), which was the hallmark of ischemia. Cases with BSS had prominent microangiopathy (61.5%, 16/26), manifested as epineurium vasculitis (inflammatory cell infiltrated to the vessel wall, obliteration and recanalization, vascular proliferation, extravascular hemosiderin deposition), angiotelectasis, proliferation and hyaline degeneration of endoneurium capillary. In the BSS group, impaired blood-nerve barrier was indicated by sub-perineurial edema (46.2%, 11/26) and endoneurial edema (15.4%, 4/26). The Renaut body (15.4%, 4/26) and amyloid deposition (3.8%, 1/26) found in the BSS group were absent in the non-BSS group.@*CONCLUSIONS@#BBS was common in non-diabetic peripheral neuropathies. The nerves exhibited ischemic alteration of primary axon degeneration and secondary demyelination. The interstitial tissue revealed microcirculation impairment, blood-nerve barrier disturbance, amyloid deposition and proliferation changes. The high prevalence of qi deficiency also highlights the therapy of promotion of blood circulation and removal of blood stasis.

Unique MicroRNAs Signature of Lymphocyte of Yang and Yin Syndromes in Acute Ischemic Stroke Patients / 中国结合医学杂志

OBJECTIVE@#To identify the differentially expressed microRNAs (miRNAs) profiles of yang and yin syndromes in patients with acute ischemic stroke, and to provide the molecular basis of the classification of these two syndrome types in acute ischemic stroke patients.@*METHODS@#A microarray assay was performed to assess the expression pattern of miRNAs in the lymphocyte of acute ischemic stroke patients. Target genes for the deregulated miRNAs were predicated using the online bioinformatic algorithms and functional annotation via Kyoto encyclopedia of genes and genomes pathway analysis for miRNAs predicted targets was carried out. Based on the predicted target genes of differentially expressed miRNAs, the miRNA-gene-network and miRNA-pathway-network were constructed.@*RESULTS@#Yang score based on tongue texture, urine, dejecta, and appearance, etc. showed that clinical symptoms were distinct between yang and yin syndromes. There were significantly higher total leukocyte number and lower total protein level in patients with yang syndrome compared with those in patients with yin syndrome (P<0.05). Comprehensive miRNA analysis identified 36 unique down-regulated miRNAs in yang syndrome group, and 20 unique down-regulated and 2 unique up-regulated miRNAs in yin syndrome group. The key regulatory miRNAs, gene, and pathways in the yang syndrome were hsa-miR-93-5p and -320b, enabled homolog, the metabolic pathways and mitogen-activated protein kinase signaling pathways, respectively, while those in the yin syndrome were hsa-miR-424-5p and -106b-5p, CNOT4, hepatitis B and pathways in cancer, respectively.@*CONCLUSION@#These results offered insight into the molecular basis underlying the different pathogenesis of yang or yin syndrome, providing clues for the individualized therapeutic strategies of acute ischemic stroke.

A pilot study on the correlation of tongue manifestation with the site of cerebral infarction in patients with stroke / 中国结合医学杂志

<p><b>OBJECTIVE</b>To discuss the correlation of tongue manifestation with the site of cerebral infarction in patients with acute cerebral infarction.</p><p><b>METHODS</b>From March 2008 to February 2009, 200 cases of hospitalized patients with first unilateral cerebral infarction were chosen in the Department of Neurology, Xuanwu Hospital. The correlation of different tongue color, fur texture, fur color with the site of cerebral infarction was analyzed.</p><p><b>RESULTS</b>The site of cerebral infarction in patients were compared between different tongue color by Chisquare test (P=0.314), and further correspondence analysis demonstrated that there was correlation between red tongue and cortical-subcortical infarction group. The site of cerebral infarction in patients were compared between thick fur group and thin fur group, cortical-subcortical infarction occurred more frequently in the former (P=0.0008). The site of cerebral infarction in patients were compared between dry fur group, moist fur group and smooth fur group, correspondence analysis demonstrated there was correlation between dry fur and cortical-subcortical group. The site of cerebral infarction in the patients were compared between white fur group, white-yellow fur group and yellow fur group (P=0.010), and correspondence analysis demonstrated there was correlation between white fur and brainstem infarction; white-yellow fur has relationship with cortical infarction; subcortical infarction was weakly related with white-yellow fur; there was closer relationship between yellow fur and cortical-subcortical infarction.</p><p><b>CONCLUSION</b>The change of tongue manifestation was associated with the site of cerebral infarction in patients, providing a new combining site for diagnosing cerebrovascular diseases by integrative medicine.</p>

A pilot study on the relationship between tongue manifestation and the degree of neurological impairment in patients with acute cerebral infarction / 中国结合医学杂志

<p><b>OBJECTIVE</b>To discuss the relationship between tongue manifestation and the degree of neurological impairment in the patients with acute cerebral infarction.</p><p><b>METHODS</b>Two hundred patients with first unilateral cerebral infarction were recruited. The relationship between different tongue manifestation and National Institute of Health Stroke Scale (NIHSS) were analyzed.</p><p><b>RESULTS</b>NIHSS scores in the patients from different tongue color groups were analyzed and further analysis demonstrated that the NIHSS score was higher in the patients with red or bluish-purple tongue than that of those with the pink (P <0.01). On tongue fur, the NIHSS score in the patients with thick fur was higher than that of those with the thin (P=0.003). NIHSS score in patients with slippery, moist or dry fur was significant different (P=0.003), Further analysis demonstrated that the NIHSS score was higher in the patients with dry fur than that of those with moist fur, and had statistical significance (P=0.01). The NIHSS score was higher in patients from greasy fur group than that of the non-greasy (P=0.002). There was significant difference of NHISS score in the patients with different fur color (P=0.000), and further analysis demonstrated that the NHISS score in white-yellow, yellow fur group were higher than that of the white (P=0.06 or 0.000).</p><p><b>CONCLUSION</b>The changes of tongue manifestation might be associated with the degree of neurological impairment in the patients with acute cerebral infarction.</p>

Study on the correlation of tongue manifestation with fibrinogen and neutrophil in acute cerebral infarction patients / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the correlation of tongue manifestation with the fibrinogen level and the neutrophil count in blood of acute cerebral infarction patients.</p><p><b>METHODS</b>A total of 200 patients with first unilateral cerebral infarction in Neurology Department of Xuanwu Hospital from March, 2008 to February, 2009 were recruited in this study. The correlation of the tongue fur color and texture with the blood fibrinogen level and the neutrophil count was analyzed in these patients.</p><p><b>RESULTS</b>The level of fibrinogen and neutrophil count in thick fur group were significantly higher than that in thin fur group (P<0.05). There was no statistical difference in the level of fibrinogen and neutrophil count found between moist fur and dry fur. Statistical significance existed in the level of fibrinogen between the greasy tongue fur group and non-greasy tongue fur group (P<0.05). The level of fibrinogen and the neutrophil count were compared among different fur color groups, revealing that the level of fibrinogen in yellowish fur group was higher than that of white fur group and normal value with statistical significance (P<0.05) with neutrophil count in yellowish fur group being significantly higher than that in white fur group.</p><p><b>CONCLUSION</b>Our results suggested that the change of tongue manifestation was associated with the level of fibrinogen and the neutrophil count in the blood of cerebral infarction patients.</p>

The effects of repetitive limb ischemia on the systemic concentration of NO, NOS in plasma of healthy humans / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of RLI on plasma nitric oxide (NO) and NO synthase (NOS) isoforms of healthy humans.</p><p><b>METHODS</b>30 healthy human subjects (aged from 40 - 70 years old) were recruited. RLI was induced by five 5 min cycles of ischemia of non dominant arm (200 mmHg, 5 min interval). Blood pressure, heart rate, and the feelings of ischemic arm were continuously monitored. Venous plasma was collected in contralateral arm at Pre, Post-0 h, Post-4 h, and Post-24 h. Plasma level of NO was measured by Griess reaction, and NOS was measured by chemical method.</p><p><b>RESULTS</b>Blood pressure and heart rate varied in normal range. The uncomfortable feeling was decreased with the increasing numbers of ischemic cycles. Plasma level of NO, and iNOS in plasma were significantly increased at Post-0 h, Post-4 h, and Post-24 h compared to Pre (P < 0.05). tNOS was also significantly increased at Post-0 h and Post-4 h compared to Pre (P < 0.05). No significant change in plasma cNOS was shown at following three time points than Pre.</p><p><b>CONCLUSION</b>These findings suggest that RLI can elevate plasma level of NO, tNOS, and iNOS in healthy humans. RLI might be a safe method as a rIPC, and it would have important possibility to be performed in clinic.</p>

Dephosphorelation of Bad and upregulation of Bcl-2 in hippocampus of rats following limbic seizure induced by kainic acid injection into amygdaloid nucleus / 生理学报

The purpose of the present study was to explore the seizure-induced changes in Bad (Bcl-2-associated death protein), 14-3-3, phosphoBad, Bcl-2 and Bcl-XL expression in the rat model of focal limbic seizure. Unilateral intra-amygdaloid injection of kainic acid (KA) was made to induce seizure. Electroencephalogram (EEG) and regional cerebral flow (r-CBF) were monitored continuously. Diazepam (30 mg/kg) was administered to terminate the seizure. The apoptotic and surviving neurons in the hippocampus were observed by terminal deoxynucleotidyl transferrase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining, the expression of Bad, 14-3-3, phosphoBad, Bcl-2 and Bcl-XL were detected with immunofluorescence, Western blot and immunoprecipitation. The results showed that TUNEL-positive neurons appeared at 8 h and reached maximum at 24 h following seizure cessation within the ipsilateral CA3 subfield of the hippocampus. Seizure induced the dephosphorylation of Bad and the dissociation of Bad from its chaperone protein 14-3-3 and subsequent dimerization of Bad with Bcl-XL. The expression of phosphoBad decreased and Bcl-2 increased. There was little change in r-CBF after the seizure. These results suggest that seizure leads to a dephosphorylation of Bad and an upregulation of Bcl-2. Dephosphorylation of Bad may be injurious while the upregulation of Bcl-2 may be protective to the brain damage induced by seizures, but not related with r-CBF.

The expression of Smac and XIAP in rat hippocampus following limbic seizure induced by kainic acid injection into amygdaloid nucleus / 生理学报

To determine whether Smac/DIABLO (second mitochondrial activator of caspases/direct inhibitor of apoptosis protein-binding protein of low isoelectric point [PI]) and XIAP (X-chromosome-linked inhibitor of apoptosis protein) serve to regulate neuronal apoptosis following seizures, we investigated seizure-induced changes in caspase-9, Smac/DIABLO and XIAP protein expression and the in vivo effect of caspase-9 inhibition. Animals received unilateral intra-amygdaloid injection of kainic acid (0.5 microg) to induce seizures for 1 h. The seizures were then terminated by diazepam (30 mg/kg). Animals were killed 0, 2, 4, 8, 24 or 72 h following diazepam administration. The apoptotic and surviving neurons in hippocampus were observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining, the expression of Smac/DIABLO, XIAP and caspase-9 was detected with immunofluorescence and western blot. The results showed that the levels of XIAP and the 46-kDa proenzyme form of caspase-9 were unaffected by the seizures. The expression of Smac increased at 2 h and the 37-kD cleaved fragment of caspase-9 was detected at 4 h, TUNEL-positive neurons appeared at 8 h and reached maximal at 24 h following seizure cessation within the ipsilateral (the same side as the intra-amygdaloid injection of kainic acid) CA3 subfield of the hippocampus. Intracerebroventricular infusion of caspase-9 inhibitor z-LEHD-fluoromethyl ketone (z-LEHD-fmk) significantly decreased TUNEL-positive neurons and increased the number of surviving cells. Caspase-9 immunoreactivity increased and Smac/DIABLO, XIAP immunoreactivity became extensive within the ipsilateral CA3 neurons. TUNEL-positive neurons and the alterations of the expression of Smac/DIABLO and XIAP within the ipsilateral CA3 were not detected within the contralateral hippocampus. These results suggest that seizures lead the translocation of Smac/DIABLO into the cytosol, the activation of caspase-9 and the change of subcellular locoalization of XIAP. These changes may play a role in the brain damage induced by seizures. Caspase-9 is possibly a potential therapeutic target in the treatment of brain injury associated with seizures.

Study of DNA damage with neuronal ischemia/reperfusion in vitro / 中国应用生理学杂志

<p><b>AIM AND METHODS</b>To investigate DNA strand damage in a model of cerebral ischemia/reperfusion injury in vitro, model of ischemia/reperfusion was produced by incubating the primary neuronal cultures to various durations of hypoxia and glucose deprivation (HGD). DNA single and double strand breaks were detected using PANT and TUNEL staining respectively.</p><p><b>RESULTS</b>A few cell death occurred after 2 h of HGD. Less than 30 percent of cell died after 4 h of HGD, whereas 6-8 h of HGD resulted in cell death in 80 percent of neurons. Neuronal cell death reached the peak 10-18 h after 6 h of HGD, while it took as early as 2 h after 8 h of HGD. Following HGD, PANT positive cells were remarkably increased, which was proportional to the duration of HGD. At 5 minutes after 2, 4, 6 or 8 h of HGD, PANT positive cells were 30%, 50%, 80%, 90% respectively. Meanwhile, no determined in another cultures, DNA double strain breaks were not significantly increased.</p><p><b>CONCLUSION</b>DNA strain breaks is a very early event of DNA damage following in vitro ischemia/reperfusion, especially DNA single strain breaks.</p>