A Missense Mutation in Epsilon-subunit of Acetylcholine Receptor Causing Autosomal Dominant Slow-channel Congenital Myasthenic Syndrome in a Chinese Family / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Congenital myasthenic syndromes are a group of rare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction. Here, we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome (SCCMS).</p><p><b>METHODS</b>Clinical characteristics and electrophysiological features of three patients from a Chinese family were examined, and next-generation sequencing followed by direct sequencing was carried out.</p><p><b>RESULTS</b>The patients revealed variability in clinical and electrophysiological features. However, weakness, scoliosis, and repetitive-compound muscle action potential were found in all affected members in the family. A heterozygous C>T missense mutation at nucleotide 865 in acetylcholine receptor epsilon-subunit (CHRNE) gene that causes a leucine-to-phenylalanine substitution at position 289 (L289F) was found.</p><p><b>CONCLUSIONS</b>We reported a SCCMS family of Chinese origin. In the family, classical clinical phenotype with phenotypic variability among different members was found. Genetic testing could help diagnose this rare disease.</p>

MRI demonstrates abnormalities of motor nerves and extraocular muscles in congenital fibrosis syndrome due to mutations in KIF21 A / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the structural basis of ocular motility abnormalities in patients with congenital fibrosis of the extraocular muscles type Ⅰ ( CFEOM Ⅰ) due to missense mutations in the developmental kinesin KIF21A using high - resolution magnetic resonance imaging ( MRI) . METHODS: Totally 11 affected individuals reported KIF21A mutations were correlated with MRI studies demonstrating extraocular muscles ( EOMs ) size, location, contractility, and innervation. EOMs and the motor nerve in the orbits were imaged with T1 weighted in a triplanar scan using a dual-phased coils with 2. 0mm thick. Motor nerves were imaged at the brainstem using head coils and 3D-FIESTA with 0. 6-mm thick. RESULTS: Patients with CFEOM Ⅰ exhibited different degrees of hypoplasia of oculomotor nerve, the abducens nerve and the trochlear nerve were also affected, of which 8 cases of orbital section could see the signal of abnormal nerve dominated by oculomotor nerve to lateral rectus. The both sides of six EOMS in all patients exhibited variable atrophy and abnormal bright internal signal on T1 imaging, particularly severe for the superior rectus and levator muscles. CONCLUSION: High - resolution MRI can directly demonstrate pathology of motor nerves,affected EOMs, and ‘Pulley' hypoplasia caused by CFEOM Ⅰ due to mutations in KIF21A,and these findings suggest that the neuronal hypoplasia is the etiological factor of CFEOM.

Magnetic resonance imaging findings in sporadic Möbius syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although neuroradiological findings of Möbius syndrome have been reported as a result of brain and brainstem abnormalities, magnetic resonance imaging (MRI) now permits the direct imaging of the cranial nerve (CN) and branches in the orbits. This study presents the MRI findings in patients with sporadic Möbius syndrome.</p><p><b>METHODS</b>Prospectively, CNs were imaged in the cistern using head coils and three dimensional fast imaging employing steady-state acquisition (3D-FIESTA), yielding a 0.5 mm(2) resolution in planes of 0.8 mm thickness in seven patients with sporadic Möbius syndrome. The cavernous and intraorbital segment of the CN and the extraocular muscles (EOMs) were imaged with T1 weighting in all patients. The cavernous segment was imaged in coronal planes, while the intraorbit in quasicoronal planes were imaged using surface coils. Intraorbital resolution was 0.16 mm(2) within 2.0 mm thick planes.</p><p><b>RESULTS</b>In the seven patients, the CN were absent or showed hypoplasia in the cistern, cavernous sinus, and orbit. Abducens (CN VI) and facial (CN VII) nerves were absent on the affected sides. Unilateral CN IX (glossopharyngeal nerve) in two cases displayed dysplasia. Branches from the inferior division of CN III were observed to innervate the lateral rectus (LR) bilaterally in three cases and unilaterally in one case, and had intimate continuity with the LR muscle in two cases bilaterally and two cases unilaterally. Hypoplasia of EOMs was shown in five cases. Dysplasia of the medulla on the left side was found in one patient.</p><p><b>CONCLUSIONS</b>Direct imaging of CNs and EOMs by MRI is useful in diagnosis of Möbius syndrome. It can directly demonstrate the abnormalities of the CN and orbital structures. The absence or hypoplasia of CN VI and CN VII may be the most common radiologic features in sporadic Möbius syndrome, and hypoplasia of CN IX may be an associated feature. The abnormality of EOMs and aberrant innervations in the orbit should be observed, and may be important for the study of the etiology.</p>

Indirubin inhibits ATP-induced phagocytosis attenuation, ROS production and cell death of macrophages / 药学学报

This study is to investigate the effects of indirubin on ATP-induced immune responses of macrophages. For this, neutral red dye uptake method was used to test phagocytosis, MTT assay was used for measuring cell death, and reactive oxygen species (ROS) was tested with fluorescent probe DHE. The data showed that extracellular ATP attenuated phagocytosis, induced cell death and increased ROS production, and these effects were restored by pre-treating with indirubin. This result suggested that indirubin blockade the effects of ATP on macrophages, because extracellular ATP-induced effects are dependent on P2 receptors, in particular P2X7 receptors. Furthermore, the effects of indirubin on the activation of P2 receptors were tested, in particular P2X7 receptors. The data showed that indirubin significantly decreased ATP-induced, P2 receptors mediated intracellular Ca2+ concentration ([Ca2+]i) rise and inhibited P2X7 receptor-based ethidium bromide (EB) dye uptake. These results suggested the inhibitory effects of indirubin on the activation of P2X7 receptors, which may underlying the effects on ATP induced ROS production, phagocytosis attenuation and cell death of macrophages.

Vertical deviation and A pattern of type III Duane retraction syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Researches in ocular electromyography (EMG) and Magnetic resonance imaging (MRI) of patients with Duane retraction syndrome (DRS) suggest that there may be additional abnormalities such as paradoxical innervation between horizontal rectus muscles and vertical rectus muscles, hypoplasia of vertical rectus muscle and that oblique muscles may also contribute to the heterogeneity of the clinical manifestation of DRS. This paper reports the results of superior rectus recession for vertical deviation and A pattern in DRS Type III and discusses the pathogenesis of the disease.</p><p><b>METHODS</b>Superior and lateral rectus recession were performed in 5 cases of Huber type III DRS to treat vertical deviation and A pattern strabismus. Before operation, MRI of the brain, brainstem, cavernous sinus, and orbits were performed.</p><p><b>RESULTS</b>All subjects had unilateral limitation of both abduction and adduction, with palpebral fissure narrowing and globe retraction in adduction. Three cases had A pattern of strabismus, three cases had hypertropia. The abducens nerves (CN6) were either absent or hypoplasitic in the brainstem in all patients. Two eyes had larger oculomotor foramen. Two eyes had hypoplasia of the superior rectus and the inferior rectus. There was presumably a branch of the third cranial nerve (CN3) innervating the lateral rectus (LR) in one eye. While in another eye, two branches of CN3 sent into medial rectus were revealed. After surgery, vertical deviation in the primary position was reduced in all patients and A pattern was eliminated in 3 patients. One patient developed 10Δ consecutive esotropia postoperatively.</p><p><b>CONCLUSION</b>The results suggest that structural abnormalities of vertical muscle and abnormal orbital innervation may be related to vertical deviation and the presence of A pattern in DRS type III. Recession of the superior rectus muscle seems to be a safe and effective treatment for vertical deviation and A pattern strabismus in DRS Type III.</p>

Indirubin inhibits ATP-induced phagocytosis attenuation, ROS production and cell death of macrophages / 药学学报

This study is to investigate the effects of indirubin on ATP-induced immune responses of macrophages. For this, neutral red dye uptake method was used to test phagocytosis, MTT assay was used for measuring cell death, and reactive oxygen species (ROS) was tested with fluorescent probe DHE. The data showed that extracellular ATP attenuated phagocytosis, induced cell death and increased ROS production, and these effects were restored by pre-treating with indirubin. This result suggested that indirubin blockade the effects of ATP on macrophages, because extracellular ATP-induced effects are dependent on P2 receptors, in particular P2X7 receptors. Furthermore, the effects of indirubin on the activation of P2 receptors were tested, in particular P2X7 receptors. The data showed that indirubin significantly decreased ATP-induced, P2 receptors mediated intracellular Ca2+ concentration ([Ca2+]i) rise and inhibited P2X7 receptor-based ethidium bromide (EB) dye uptake. These results suggested the inhibitory effects of indirubin on the activation of P2X7 receptors, which may underlying the effects on ATP induced ROS production, phagocytosis attenuation and cell death of macrophages.

Magnetic resonance imaging of unilateral vertical retraction syndrome with atypical strabismus / 中华医学杂志(英文版)

We report two patients with unilateral vertical retraction syndrome. Magnetic resonance imaging (MRI) of the orbits of the two cases showed similar size and location of the orbital structure, but with dramatically different strabismus type. MRI sagittal reconstruction of the orbits suggested that abnormal muscle tissue arised from the inferior rectus, which might be associated with retraction and narrowing of the palpebral fissure and atypical strabismus as well.

Effect of von Willebrand factor on the biological characteristics of colorectal cancer cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study effect of von Willebrand factor (vWF) on the proliferation, adhesion and migration of human colorectal cancer cells.</p><p><b>METHODS</b>Human colorectal cancer cell line SW480 was cultured in vitro, and the expression of vWF in SW480 cells was detected by immunocytochemistry. SW480 cells were treated with vWF antibody (vWFAb), and the morphological change was examined by inverted microscope. Cell proliferation and ability to adhere extracellular matrix IIII( collagen were detected with MTT. Migration ability of SW480 cells was assayed by Transwell.</p><p><b>RESULTS</b>The human colorectal cancer cell line SW480 expressed vWF which was mainly in nucleus and slightly in cytoplasm. vWFAb significantly inhibited the proliferation ability of SW480 cells in dose- and time-dependent manner (P<0.05). After vWFAb treatment, SW480 cells adhesion decreased significantly (P<0.05), and transmembrane migration of cells significantly decreased (54.60+/-11.01 vs 97.27+/-10.01, P<0.01).</p><p><b>CONCLUSIONS</b>Human colorectal cancer cells can express vWF. vWF in human colorectal cancer cells plays an important role in promoting proliferation, adhesion, and migration.</p>

Magnetic resonance imaging of the extraocular muscles and corresponding cranial nerves in patients with special forms of strabismus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With the technical advances, magnetic resonance imaging (MRI) is now sensitive enough to detect subtle structural abnormalities of ocular motor nerves arising from the brainstem and orbits of living subjects. This study was designed to delineate the MRI characteristics in patients with special forms of strabismus.</p><p><b>METHODS</b>A total of 29 patients with special forms of strabismus underwent orbital and intracalvarium MRI. Imaging of the ocular motor nerves in the brainstem was performed in 0.8 mm thickness image planes using the three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA) sequence. Nerves to extraocular muscles (EOMs), EOMs and their associated connective tissues were imaged with T1 weighting in tri-planar scans by dual-phased coils within 2.0 mm thick planes.</p><p><b>RESULTS</b>Patients with congenital fibrosis of the extraocular muscles exhibited hypoplasia of the oculomotor (CN3), abducens (CN6), trochlear (CN4) nerves, and the EOMs; hypoplasia of CN6 in the brainstem and an extra branch of the inferior division of CN3 to the lateral rectus were the most common but not the only presentation of Duane's retraction syndrome. Hypoplasia of CN6, facial (CN7) and hypoglossal (CN12) nerves were revealed in patients with Möbius syndrome. In a rare case of bilateral synergistic convergence and divergence, an enlarged branch of CN3 to the medial rectus and a questionable branch of CN3 to the inferior rectus bilaterally were found.</p><p><b>CONCLUSION</b>MRI can reveal subtle structures of the ocular motor nerves and their corresponding EOMs. This can provide valuable information regarding pathogenesis in some special forms of strabismus.</p>

Study on the relationship among the NF-?B activation,uPA expression and apoptosis induced by 5- Fu in HCT116 human carcinoma cell line / 肿瘤研究与临床

Objective To study the relationship among apoptosis,NF-KB activation and uPA expres- sion in human colon carcinoma cell line HCTll6 induced by 5-fluorouracil,and to observe the effect of in- hibiting activity of NF-KB by PDTC on apoptosis as well as expression of uPA.Methods Cell apoptosis was analysed by Annexin V-FITC.Fluctuation of NF-KB and uPA was detected by semi-quantitative immuno- histochemistry.Results 5-fluorouracil could induce apoptosis and activate NF-KB.PDTC could significantly increase the apoptosis and suppress the activation of NF-KB induced by 5-fluorouracil.There was a positive correlation between the changes of uPA and NF-KB.Conclusion 5-fluorouracil could induce apoptosis,ac- tivate NF-KB and up-regulate expression of uPA of HCT116 cells.The mechanism of enhanced apoptosis by PDTC may be related to suppressing activation of NF-?B and down-regulating expression of uPA.