Neurochondrin Antibody Serum Positivity in Three Cases of Autoimmune Cerebellar Ataxia.

To report three cases of autoimmune ataxia patients with positive neurochondrin (NCDN) antibodies. Patients with unknown cerebellar ataxia were screened for autoimmune cerebellar ataxia (ACA)-related antibodies, including glutamic acid decarboxylase 65 (GAD65), delta/notch-like epidermal growth factor-related receptor (Tr/DNER), zinc finger protein 4 (ZIC4), inositol 1,4,5-triphosphate receptor 1 (ITPR1), Homer protein homologue 3 (Homer-3), neurochondrin (NCDN), Purkinje cell antibody 2 (PCA-2) and carbonic anhydrase-related protein VII (CARPVII). The antibodies were assessed by indirect immunofluorescence using transfected cells (cell-based assay, CBA) and monkey cerebellum (tissue-based assay, TBA) with the multi-antigen co-plate biochip mosaic technique. Patients with positive antibodies received immunotherapy and were followed up in the clinic. Clinical characteristics, laboratory data, and outcomes of antibody-positive patients were described, analysed and compared with previously reported cases. The NCDN antibody was positive in three male patients in whom the onset ages were four years and 11 months, two years and seven months and 67 years old. Serum antibody titres were 1:32, 1:100 and 1:320. Cerebral ataxia was the most prominent presentation. Cerebellar atrophy was found in one of the patients. Immunotherapy was effective in all three patients. The NCDN antibody is associated with autoimmune ataxia, and it has been suggested that the NCDN antibody should be tested in patients with cerebellar ataxia who are negative for routine ACA antibodies. Early immunotherapy may have a beneficial impact on prognosis.

Kinase-Inactivated EGFR Is Required for the Survival of Wild-Type EGFR-Expressing Cancer Cells Treated with Tyrosine Kinase Inhibitors.

Inhibiting the tyrosine kinase activity of epidermal growth factor receptor (EGFR) using small molecule tyrosine kinase inhibitors (TKIs) is often ineffective in treating cancers harboring wild-type EGFR (wt-EGFR). TKIs are known to cause dimerization of EGFR without altering its expression level. Given the fact that EGFR possesses kinase-independent pro-survival function, the role of TKI-inactivated EGFR in cancer cell survival needs to be addressed. In this study, using wt-EGFR-expressing cancer cells A549 (lung), DU145 (prostate), PC3 (prostate), and MDA-MB-231 (breast), we characterized the TKI-induced dimerization status of EGFR and determined the dependency of cells on kinase-inactivated EGFR for survival. We report that TKI-induced EGFR dimerization is dependent on palmitoylation and independent of its kinase activity, and that mutations of the cysteine residues known to be critical for EGFR's palmitoylation abolished TKI-induced EGFR dimerization. Furthermore, TKI-induced EGFR dimerization is persistent in TKI-resistant cells, and inhibition of palmitoylation by 2-bromopalmitate, or targeted reduction of the kinase-inactivated EGFR by siRNA or by an EGFR-downregulating peptide, are lethal to TKI-resistant cancer cells. This study suggests that kinase-inactivated EGFR remains to be a viable therapeutic target for wt-EGFR cancers and that inhibiting palmitoylation or downregulating EGFR may overcome TKI resistance.

EGFR-SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors.

BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) is associated with poor prognosis in malignant tumors. Sodium/glucose co-transporter 1 (SGLT1) is an active glucose transporter that is overexpressed in many cancers including prostate cancer. Previously, we found that EGFR interacts with and stabilizes SGLT1 in cancer cells. METHODS: In this study, we determined the micro-domain of EGFR that is required for its interaction with SGLT1 and the effects of activation/inactivation of EGFR on EGFR-SGLT1 interaction, measured the expression of EGFR and SGLT1 in prostate cancer tissues, and tested the effect of inhibition of SGLT1 on the sensitivity of prostate cancer cells to EGFR tyrosine inhibitors. RESULTS: We found that the autophosphorylation region (978-1210 amino acids) of EGFR was required for its sufficient interaction with SGLT1 and that this interaction was independent of EGFR's tyrosine kinase activity. Most importantly, the EGFR-SGLT1 interaction does not respond to EGFR tyrosine kinase modulators (EGF and tyrosine kinase inhibitors). EGFR and SGLT1 co-localized in prostate cancer tissues, and inhibition of SGLT1 by a SGLT1 inhibitor (Phlorizin) sensitized prostate cancer cells to EGFR inhibitors (Gefitinib and Erlotinib). CONCLUSION: These data suggest that EGFR in cancer cells can exist as either a tyrosine kinase modulator responsive status or an irresponsive status. SGLT1 is a protein involved in EGFR's functions that are irresponsive to EGFR tyrosine kinase inhibitors and, therefore, the EGFR-SGLT1 interaction might be a novel target for prostate cancer therapy.

Pediatric anti-N-methyl-D-aspartate receptor encephalitis with MOG-Ab co-existence: Relapse propensity and treatability.

OBJECTIVES: To investigate the clinical characteristics of the anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis with anti-myelin oligodendrocyte glycoprotein antibody(MOG-Ab)positivity serostatus in pediatric patients. METHODS: The clinical manifestations, treatments, and outcomes of patients with anti-NMDAR encephalitis with positive MOG-Ab were elaborated. The annualized relapse rates (ARRs) were compared before and during treatment with disease-modifying drugs (DMDs). RESULTS: Twelve patients were included. In the prospective cohort(Cohort A), MOG-Ab positivity was associated with relapse (p = 0.028, OR = 1.677). Eight cases relapsed, of which six cases were treated with DMDs. The median ARR reduced significantly following DMDs treatments (z = 1.992, P = 0.046). CONCLUSIONS: The anti-NMDAR encephalitis patients with MOG-Ab co-existence are prone to relapse. Long-term DMDs therapy can reduce ARRs.

Autoimmune cerebellar ataxia associated with anti-leucine-rich glioma-inactivated protein 1 antibodies: Two pediatric cases.

OBJECTIVES: To report two pediatric cases of autoimmune cerebellar ataxia associated with the anti-Leucine-rich glioma-inactivated protein 1 (LGI1)antibodies. METHODS: The clinical features of the two patients were described retrospectively. The indirect immunofluorescence using transfected cells (cell-based assay, CBA) and the rat cerebellum (tissue-based assay, TBA) with the multi-antigen co-plate biochip mosaic techniques were used to detect the antibodies. Clinical and laboratory characteristics were described. RESULTS: Two males were included. The onset ages were 2.7y and 4y, respectively. Patient 1 manifested as isolated acute cerebellar ataxia. Patient 2 had extra-cerebellar symptoms, including seizures, encephalopathy, faciobrachial dystonic seizures(FBDs), and significant cerebellar ataxia. The hyponatremia and tumors were not found. Both of them responded well to the immunotherapy. CONCLUSIONS: The autoimmune cerebellar ataxia might be a new phenotype of LGI1-Abs autoimmunity in children.

Loss of EGFR induced autophagy sensitizes hormone refractory prostate cancer cells to adriamycin.

BACKGROUND: The epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is over-expressed in advanced prostate cancer but tyrosine kinase inhibitors are not clinically effective in the treatment of prostate cancer. Recently it was found that EGFR in cancer cells has a kinase-independent pro-survival function, preventing cells from undergoing autophagy. In the present study we investigated whether the anti-autophagic function of EGFR may contribute to resistance of hormone-refractory prostate cancer cells to chemotherapeutic-induced apoptosis. METHODS: We first characterized the autophagic phenotype induced by knocking down EGFR in hormone refractory prostate cancer cells (PC-3MM2 and DU-145), then we tested whether loss of EGFR-induced autophagy could sensitize cancer cells to adriamycin. RESULTS: Using continuous live cell imaging techniques, we observed that knocking down EGFR lead to typical autophagic morphological/molecular changes, cell shrinkage without detachment, aggregation of microtubule-associated protein 1 light chain 3 (LC3) protein and absence of activation of apoptotic caspases 3/7. Loss of EGFR also increased the activity of calpain, which is pro-apoptotic. Knocking down EGFR, but not inhibiting its tyrosine kinase activity, significantly sensitized cells to adriamycin-induced apoptosis. Adriamycin-induced apoptosis could be inhibited by increased extracellular glucose level, suggesting intracellular glucose deficiency is a key mediator of the sensitization. The loss of EGFR induced autophagy and sensitization to adriamycin were also reproduced by using another hormone refractory prostate cancer cell line, Du145. CONCLUSION: Taken together, these data suggest that decreasing the expression level of EGFR protein, rather than inhibiting its tyrosine kinase activity, may enhance the efficiency of EGFR targeted therapy for prostate cancer.

Formation of solid tumors by a single multinucleated cancer cell.

BACKGROUND: Large multinucleated cells (MNCs) commonly exist in tumorigenic cancer cell lines that are used widely in research. However, the contributions of MNCs to tumorigenesis are unknown. METHODS: In this study, MNCs were characterized in the murine fibrosarcoma cell line UV-2237 in vitro and in vivo at the single-cell level. RESULTS: The authors observed that MNCs originated from a rare subpopulation of mononuclear cells and were positive for a senescent marker, ß-galactosidase. In addition, MNCs were responsible for the majority of clonogenic activity when cultured in hard agar; they were more resistant to chemotherapeutic agents than mononuclear cells; they could undergo asymmetric division (producing mononuclear cells) and self-renewal in vitro and in vivo; and, most important; a single MNC produced orthotopic, subcutaneous tumors (composed mainly of mononuclear cells) that gave rise to spontaneous lung metastases in nude mice. CONCLUSIONS: The current results indicated that the growth of MNCs may be arrested under stress and that MNCs are highly resistant to chemotherapy and can generate clonal, orthotopic, metastatic tumors.

The Chinese version of the Personal and Social Performance Scale (PSP): validity and reliability.

The Personal and Social Performance Scale (PSP) is a 100-point single-item rating scale that assesses four important domains of patients with mental disorders. This study was designed to examine the validity and reliability of a Chinese version of the PSP. The study was conducted in a sample of 157 patients with schizophrenia (confirmed by DSM-IV-TR criteria, SCID-P interview). The internal consistency (Cronbach's alpha=0.84) and the inter-rater reliability (kappa value=0.82, ICC=0.94 for PSP total score) was good. The test-retest reliability was high (intraclass correlation coefficient (ICC) of 0.95). The scale showed good construct validity with statistically significant correlations with the Global Assessment of Functioning Scale (GAF) (ICC of 0.95). The PSP score had a good negative correlation with the Positive and Negative Syndrome Scale (PANSS) total score. The improvement in PSP after 8 weeks of treatment was significantly correlated with the reduction in PANSS: after 8 weeks of treatment, the responders (defined as those with a reduction in PANSS total score ≥50%) experienced a greater improvement in PSP than the non-responders. The Chinese version of the PSP is a convenient and valid instrument to assess the personal and social functions of stabilized and acute patients with schizophrenia.

PKCδ-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs.

The tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have been widely used for non-small cell lung cancer (NSCLC) patients, but the development of acquired resistance remains a therapeutic hurdle. The reduction of glucose uptake has been implicated in the anti-tumor activity of EGFR TKIs. In this study, the upregulation of the active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with the poorer clinical outcome of the NSCLC patients who received EGFR TKI treatment. Blockade of SGLT1 overcame this resistance in vitro and in vivo by reducing glucose uptake in NSCLC cells. Mechanistically, SGLT1 protein was stabilized through the interaction with PKCδ-phosphorylated (Thr678) EGFR in the TKI-resistant cells. Our findings revealed that PKCδ/EGFR axis-dependent SGLT1 upregulation was a critical mechanism underlying the acquired resistance to EGFR TKIs. We suggest co-targeting PKCδ/SGLT1 as a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.

Rethink of EGFR in Cancer With Its Kinase Independent Function on Board.

The epidermal growth factor receptor (EGFR) is one of most potent oncogenes that are commonly altered in cancers. As a receptor tyrosine kinase, EGFR's kinase activity has been serving as the primary target for developing cancer therapeutics, namely the EGFR inhibitors including small molecules targeting its ATP binding pocket and monoclonal antibodies targeting its ligand binding domains. EGFR inhibitors have produced impressive therapeutic benefits to responsive types of cancers. However, acquired and innate resistances have precluded current anti-EGFR agents from offering sustainable benefits to initially responsive cancers and benefits to EGFR-positive cancers that are innately resistant. Recent years have witnessed a realization that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. This new knowledge has offered a different angle of understanding of EGFR in cancer and opened a new avenue of targeting EGFR for cancer therapy. There are already many excellent reviews on the role of EGFR with a focus on its kinase-dependent functions and mechanisms of resistance to EGFR targeted therapies. The present opinion aims to initiate a fresh discussion about the function of EGFR in cancer cells by laying out some unanswered questions pertaining to EGFR in cancer cells, by rethinking the unmet therapeutic challenges from a view of EGFR's KID function, and by proposing novel approaches to target the KID functions of EGFR for cancer treatment.

Learning Curve for Using Endoscopic Saphenous Vein Harvesting in Coronary Artery Bypass Grafting / 中山大学学报(医学科学版)

ObjectiveTo investigate the application of endoscopy in obtaining the great saphenous vein （GSV） during coronary artery bypass grafting （CABG） and explore the learning curve， with a particular focus on common challenges encountered during the learning process and their impact on early clinical outcomes. MethodsA retrospective analysis was conducted on clinical data from 83 patients who underwent off-pump CABG with endoscopic GSV harvesting at the First Affiliated Hospital of Zhengzhou University from July 2013 to April 2014. Patients were categorized into four groups based on the chronological order of their hospitalization： Group A （novice group， n=20）， Group B （proficient group， n=20）， Group C （progressive group， n=20）， and Group D （mature group， n=23）. Differences in perioperative and midterm follow-up outcomes among the groups were analyzed to determine the learning curve period. ResultsThe study population had a mean age of （60.22±8.06） years and a mean body weight of （69.77±11.66） kg. Comorbidities included hypertension （24 cases）， diabetes （26 cases）， and subacute cerebral infarction （14 cases）. The novice group exhibited significantly shorter GSV length-to-harvest time ratio relative to the other three groups （P<0.001） and a significantly higher incidence of main vein damage （P=0.006）. However， there was no statistically significant difference in graft patency at the 1-year follow-up. ConclusionThorough and reliable technical training in endoscopic GSV harvesting is essential to minimize vascular injury caused by novice operators. Approximately 20 cases of hands-on experience and a careful self-analysis of procedural challenges are likely required to achieve proficiency in GSV harvesting.

Effect of online and offline collaborative and integrated mode on voluntary blood donation: Internet + blood donation souvenir / 中国输血杂志

【Objective】 To explore the effect of online and offline collaborative and integrated mode (Internet + blood donation souvenirs), and develop diversified scientific ways of caring for voluntary blood donors in combination with the potential expectation of the target population, ao as to recruit and retain more blood donors. 【Methods】 A total of 4 000 blood donors from Yichang Central Blood Station from January 1 to June 30, 2022 were selected, and they could collect souvenirs from online and offline. The intelligent platform V9.5 of modern blood station management information system of Qiao Technology was used to classify the data of online and offline souvenir distribution, and digital intelligent comparison and analysis on age, occupation, education, type (first-time blood donors or repeat blood donors), region (main urban districts of Yichang and other counties and suburban districts) and gender were carried out. 【Results】 A total of 1 400 blood donors chose online souvenirs, who were mainly under 25 years old, students, female, college education or above, urban areas and regular donors; 2 600 chose offline souvenirs, who were mainly over 25 years old, male, junior college degree or below, occupations other than students (medical workers, educators, etc.), counties and suburban districts, and first-time blood donors. The collaborative and integrated mode of the two distribution methods were complementary and had a good incentive effect on blood donor recruitment. 【Conclusion】 The online and offline collaborative and integrated mode demonstrates a good effect and meets the needs of different population. Digital intelligence system is helpful to develop diversified and scientific ways of caring for voluntary blood donors, recruit and retain more blood donors, achieve high-quality development of blood collection and supply, therefore guarantee the increasing demand for clinical blood use.

Targeted reduction of the EGFR protein, but not inhibition of its kinase activity, induces mitophagy and death of cancer cells through activation of mTORC2 and Akt.

The oncogenic epidermal growth factor receptor (EGFR) is commonly overexpressed in solid cancers. The tyrosine kinase activity of EGFR has been a major therapeutic target for cancer; however, the efficacy of EGFR tyrosine kinase inhibitors to treat cancers has been challenged by innate and acquired resistance at the clinic. Accumulating evidence suggests that EGFR possesses kinase-independent pro-survival functions, and that cancer cells are more vulnerable to reduction of EGFR protein than to inhibition of its kinase activity. The molecular mechanism underlying loss-of-EGFR-induced cell death remains largely unknown. In this study, we show that, unlike inhibiting EGFR kinase activity that is known to induce pro-survival non-selective autophagy, downregulating EGFR protein, either by siRNA, or by a synthetic EGFR-downregulating peptide (Herdegradin), kills prostate and ovarian cancer cells via selective mitophagy by activating the mTORC2/Akt axis. Furthermore, Herdegradin induced mitophagy and inhibited the growth of orthotopic ovarian cancers in mice. This study identifies anti-mitophagy as a kinase-independent function of EGFR, reveals a novel function of mTORC2/Akt axis in promoting mitophagy in cancer cells, and offers a novel approach for pharmacological downregulation of EGFR protein as a potential treatment for EGFR-positive cancers.

Apoptotic cells initiate endothelial cell sprouting via electrostatic signaling.

Angiogenesis, the development of new blood vessels from preexisting vessels, is crucial to tissue growth, repair, and maintenance. This process begins with the formation of endothelial cell sprouts followed by the proliferation and migration of neighboring endothelial cells along the preformed extensions. The initiating event and mechanism of sprouting is not known. We show that the phenotypic expression of negatively charged membrane surface in apoptotic cells initiates the formation of directional endothelial cell sprouts that extend toward the dying cells by a mechanism that involves endothelial cell membrane hyperpolarization and cytoskeleton reorganization but is independent of diffusible molecules.

Analysis of IQSEC2 gene variant in a child with X-linked mental retardation / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic variants of a child with X-linked mental retardation caused by IQSEC2 gene mutation, and provide reference for the diagnosis of the disease.@*METHODS@#The child was subjected to next generation sequencing (NGS), and the diagnosis was made by taking consideration of her clinical characteristics.@*RESULTS@#The child has presented with global developmental delay, particularly in fine motor skill and language development, in addition with intellectual disability. Genetic testing revealed that she has harbored a heterozygous c.1861dup variant of the IQSEC2 gene, which was not detected in either parent.@*CONCLUSION@#The de novo c.186ldup variant of the IQSEC2 gene probably underlay the X-linked mental retardation in this child. Above finding has, expanded the spectrum of IQSEC2 gene mutations and provide a basis for the diagnosis of similar cases.

Effect of information management mode based on WeChat platform on patients with mild to moderate chronic obstructive pulmonary disease / 中华健康管理学杂志

Objective:To evaluate the effect of management mode based on WeChat platform on patients with mild to moderate chronic obstructive pulmonary disease (COPD).Methods:A total of 100 patients with mild to moderate COPD treated in the outpatient or ward of the Respiratory Department of Shangqiu First People′s Hospital from January 2019 to January 2020 were included. According to the randomization criteria singular number (observation group, control group), there were 50 cases in each group. The control group received routine outpatient treatment and health education follow-up, the observation group was enrolled into the WeChat management group of COPD based on the same treatment as the control group. Smoking cessation, eight-item Morisky Medication Adherence Scale (MMAS-8) score for inhaled drug compliance, chronic obstructive pulmonary disease assessment test (CAT) questionnaire score, 6 min walking distance (6MWD) and lung function [forced expiratory volume in the first second (FEV 1) and FEV 1%pred] were compared between 2 groups before and after six months intervention. Results:After intervention, the intervention follow-up was completed in 46 patients in the observation group and 35 patients in the control group, the rate of loss to follow-up in the observation group was lower than that in the control group (8% vs. 30%) ( P<0.05); The success rate of smoking cessation, the score of MMAS-8, the score of CAT, the FEV 1 and FEV 1%pred in the observation group were higher than those in the control group [82.4% vs 53.6%, (5.17±1.06) vs (4.55±0.94) points, (6.72±4.29) vs (9.37±4.54) points, (1.87±0.44) vs (1.64±0.41) L, (69.48±10.97) vs (64.46±8.25)%] (all P<0.05). There was no significant difference in 6MWD between the observation group and the control group [(401.5±92.3) vs (382.9±79.7) m] ( P>0.05). Conclusion:Management intervention based on WeChat platform can improve the smoking cessation rate and medication compliance of patients with mild to moderate COPD, so as to reduce the symptoms of dyspnea and delay the decline of pulmonary function.

Clinical application of the new classification criteria in children with Miller Fisher syndrome and clinical characteristics analysis of different types of Miller Fisher syndrome / 中华实用儿科临床杂志

Objective:To investigate the clinical application of the new classification criteria in children with Miller Fisher syndrome (MFS), and to analyze clinical characteristics of different types of MFS.Methods:Clinical data of MFS patients hospitalized in the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from January 2015 to December 2019 were collected and analyzed retrospectively, including demographic characteristics, clinical symptoms, neurological examination findings, laboratory examination data, diagnosis and treatment, and prognosis.The counting data was described by percentage, and the measurement data was described by median.Results:A total of 23 patients were included in the research, including 14 males and 9 females, with a median age of 4 years and 8 months.There were 3 cases of pure MFS; 5 cases of incomplete MFS, including 1 case of acute ptosis and 4 cases of acute ataxia neuropathy; 15 cases of overlapping syndrome, including 13 cases of MFS/Guillain Barre syndrome (GBS), 1 case of MFS/pharyngocervical brachial variant GBS(PCB GBS)and 1 case of MFS/GBS/Bickertaff brainstem encephalitis (BBE). In addition to Ⅲ, Ⅳ and Ⅵ cranial nerve palsy, 11 cases had the involvement of other cra-nial nerves, including 2 cases in pure MFS, 8 cases in MFS/GBS and 1 case in MFS/GBS/BBE.Autonomic nervous dysfunction occurred in 6 cases.Respiratory muscle paralysis occurred in 6 cases, including 5 cases in MFS/GBS and 1 case in MFS/GBS/BBE.Graded by the Hughes scoring system (HG score), 3 cases with pure MFS were graded 4 points; 1 case with acute ptosis was graded 0; 3 cases with acute ataxia neuropathy were graded 2 points, and the other one was graded 3 points; 1 case with MFS/PCB GBS was graded 3 points; 10 cases with MFS/GBS were graded 4 points, 1 case was graded 3 points, and the other 2 cases were graded 2 points; 1 case with MFS/GBS/BBE was graded 4 points.Twenty-two patients were treated with intravenous immunoglobulin.The HG of all patients at discharge decreased at varying degree, which was graded 0 at 6 months of follow-up.Conclusions:The clinical application of the new diagnostic classification method is helpful to the accurate diagnosis of different types of MFS.More than half of MFS cases will develop into the overlapping syndrome.The overlapping of MFS and GBS or BBE is prone to the involvement of cranial nerves except for the external ophthalmic muscles, autonomic nerve dysfunction and respiratory muscle paralysis.The disease course of MFS varies, and its diagnosis should be comprehensively made.All cases of MFS in this study have a satisfactory prognosis.

Clinical features and gene mutation analysis of a male case of subcortical band heterotopia caused by mosaic mutation of DCX gene / 中华神经科杂志

Objective:To investigate the clinical phenotype and genotype of a male case of subcortical band heterotopia caused by mosaic mutation of DCX gene.Methods:The clinical data and magnetic resonance imaging (MRI) features of a male case of subcortical band heterotopia diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in August 2020 were analyzed retrospectively. At the same time, the whole exon sequencing of the families was performed by next generation sequencing method, the suspicious mutation was verified by polymerase chain reaction Sanger sequencing, and their genetic mutation characteristics were analyzed.Results:The proband, one male, aged 5 years and 1 month, was hospitalized in August 2020 with the complaint of intermittent convulsions for 4 years and six months. Clinical features included that limb muscle tension was slightly high, intellectual and motor development was backward, and head circumference was 48 cm. MRI of his head showed diffuse thick subcortical band heterotopia. The detection of whole exon sequencing in his family showed that there was hemizygous mosaic mutation in DCX gene (mosaic ratio 44%), c.148A>G (p.k50E). The mosaic ratios of oral mucosa and urinalysis were 38.2% and 44.8% respectively. His parents were wild-type, The mutation found in this patient has not been reported at home and abroad.Conclusions:The mosaic variation of DCX gene can cause subcortical band heterotopia in males. The variation of DCX gene c.148A>G (p.k50E) may be the possible cause of the proband, which expands the variation spectrum of subcortical band heterotopia.

A case of febrile infection-related epilepsy syndrome in children successfully treated with tocilizumab and literature review / 中华神经科杂志

Objective:To report a case of tocilizumab successfully used in a child with febrile infection-associated epilepsy syndrome (FIRES), and to provide a new idea for the treatment of FIRES in children.Methods:The diagnosis and treatment of 1 case of FIRES admitted in Children′s Hospital Affiliated to Zhengzhou University on February 15, 2021 were described, and the prognosis and follow-up of the child were evaluated. At the same time, the literatures on tocilizumab in the treatment of children′s FIRES were reviewed.Results:A 5-year-old case of FIRES was reported. The child was extremely refractory to immunotherapy and anti-seizure medicines, anesthetics and ketogenic diet. So he was treated with tocilizumab (each time 4 mg/kg) at the 36th day and 43rd day, and epileptic seizures were controlled 10 days after the 2nd doses of tocilizumab. During a follow-up of 10 months, his epileptic seizures were controlled and the cognitive behavior and speech function were well recovered. At present, only 3 cases of FIRES in children have been reported all over the world. All the seizures were well controlled and no obvious adverse reactions were observed.Conclusions:FIRES is a rare refractory epilepsy syndrome, resistant to many kinds of anti-seizure medicines or even anesthetic agents, which is difficult to treat and has poor prognosis. Preliminary trials have shown that tocilizumab is effective and well tolerated in children with FIRES. It may be a potential therapeutic modality for children with FIRES.

Phenotype and genotype features of 11 children with dystonia 28 caused by KMT2B variants / 中华实用儿科临床杂志

Objective:To summarize the clinical characteristics of children with dystonia 28 (DYT28) caused by KMT2B gene variations so as to improve clinicians′ understanding of the disease. Methods:The clinical manifestations, treatment and gene variation data of 11 children with DYT28 caused by KMT2B gene variations were retrospectively collected and analyzed.The subjects were recruited from the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from March 2018 to January 2021.The patients were followed up. Results:There were 8 males and 3 females.The age at onset was ranging from 1 month to 6 years without inducement.Eight cases were gene-ralized dystonia and 3 cases were multifocal dystonia.The initial symptoms of 7 cases were unilateral or bilateral lower limbs tiptoeing.Four cases presented dysarthria, retching or swallowing difficulties at onset.As the disease progressed, all the cases had laryngeal dystonia, 10 cases had lower limbs dystonia, and 8 cases had upper limbs dystonia.Six cases were complicated with other dyskinesia symptoms.Ten cases had varying degrees of short stature, microcephalus, micrognathia, musculoskeletal abnormalities, intellectual disability, endocrinopathies and sleep difficulties.The brain magnetic resonance imaging showed abnormal in only 1 case.Eleven KMT2B gene pathogenic variants were found, including 8 frameshift variants, 1 in-frame variant and 2 missense variants.Four variants were novel.Eleven cases were followed up at the age of 1 year and 7 months to 17 years and 9 months.One case wasn′t given therapy.The dystonia in 3 cases was mildly improved after medication.Dysfunction of urination and defecation was disappeared in 1 case after medication.The symptom of 6 cases had no improvement after drug therapy.Among the above 6 cases, 5 drug refractory cases had deep brain stimulation, and their dystonia symptoms are all obviously improved; 2 cases had normal control of urination and defecation after deep brain stimulation.The motor scores in the Burke-Fahn-Marsden dystonia rating scale were improved by 55.8%-90.7%, and the disability scores were improved by 14.8%-69.6%. Conclusions:DYT28 caused by KMT2B gene variations is one of the most common and early-onset genetic dystonia in children.The dystonia symptom progresses from local parts to the whole body, prominently involving laryngeal muscles and lower limbs.Control of urination and defecation requires attention.Patients with mild dystonia symptoms can be effectively treated by drugs.However, patients with severe dystonia symptoms were drug refractory, and their dystonia symptoms can be effectively improved by deep brain stimulation.