This article reports a case of limb-girdle muscular dystrophy type 1B (LGMD1B) caused by a novel splicing heterozygous mutation in the LMNA gene. The proband presented with progressive aggravation of weakness in walking. There was no atrophy of the scapular muscles and the lower-extremity proximal muscles, with normal muscle tension of the extremities, grade 4 muscle strength in the upper and lower extremities, and positive Gower sign. The level of creatine kinase was 779 U/L. Muscle hematoxylin-eosin staining showed muscular dystrophy, and there was no significant reduction in the expression of Lamin A protein. Second-generation sequencing revealed a novel splicing heterozygous mutation, c.810+2T>C, in the LMNA gene, while this locus was normal in his parents. GERP++RS software predicted that the mutation site was highly conservative. Human Splice Finder and Spliceman software predicted that the mutation might be a pathogenic mutation. ExPASy software predicted that the new amino acid sequence became shorter. There were two sequences of mRNA in the patient's muscle: one was the normal sequence, which accounted for 92.2%; the other was partial intron 4 retention, which was the abnormal splice variant accounting for 7.8%. LGMD1B is a type of autosomal dominant inherited myopathy caused by a mutation in the LMNA gene located on the autosomal 1q22. This study extends the mutation spectrum of the LMNA gene and provides help to the diagnosis of LGMD1B.
Amino Acid Sequence ; Humans ; Lamin Type A ; Muscular Dystrophies, Limb-Girdle ; Mutation

[Objective]To investigate the etiology,clinical manifestation,treatment and prognosis of optic disc vas-culitis.[Method]Twenty-four eyes of 21 patients were enrolled in this retrospective study.Eye examinations,treatment, and effect were recorded.[Result]Six were male and 15 were female.The age was between 19 and 43 years old(average:28.7±1.6).85.7% of the patients referred to the clinic with mild to moderate decreased vision.Edema of the optic disc can be seen in both types while tortuous veins can also be found in type 2.Similar characteristics were noticed in OCT,FFA, and etc.With a follow-up of 4.52±0.98 months after treatment(prednisone:initial dose 1.0-1.2 mg/kg),the BCVA of the affected eyes improved significantly.[Conclusion]Optic disc vasculitis is affected by autoimmune disorder,infection,hy-perlipidemia,and etc.Edema of the optic disc with/without tortuous veins and retinal hemorrhage can be noticed.Similar diseases should be excluded in avoidance of misdiagnosis. Systemic examination and complete solution should be per-formed.Glucocorticoid helps to improve the visual function.The application of anti-VEGF is effective in secondary macu-lar edema.However,the long-term efficacy is awaiting being confirmed.

OBJECTIVETo investigate the influence of avian influenza virus (AIV) NS1 protein on the expression of interferon-inducible protein 10 (IP-10).

METHODSNSI gene from virus A/Anhui/1/2005 (H5N1), NS1 gene inserted with 80-84 amino acids from virus A/Anhui/1/2005 (H5N1) and NS1 gene from virus A/Puerto Rico/8/1934 (H1N1) were cloned into the eukaryotic expression vector pEGFP-N1, and transfected into BEAS-2B cells, IP-10 expression level in transfected cells was detected by flow cytometry.

RESULTSCompared with the control group pEGFP-N1, expression of these three different NS1 genes can down-regulate the expression of IP-10 in BEAS-2B cells, but there is no significant difference as to the lower level among them.

CONCLUSIONNS1 protein of A/Anhui/1/2005 (H5N1) can down-regulate the expression level of IP-10, but this may not clarify its relationship with the virulence of AIV.

Cell Line ; Chemokine CXCL10 ; genetics ; metabolism ; Down-Regulation ; Gene Expression ; Humans ; Influenza A Virus, H5N1 Subtype ; genetics ; metabolism ; Influenza, Human ; genetics ; metabolism ; virology ; Viral Nonstructural Proteins ; genetics ; metabolism

OBJECTIVETo study the changes in serum levels of cortisol and adrenocorticotropic hormone (ACTH) in children with septic shock (SS) and to explore their relationship with the disease severity and prognosis.

METHODSTwenty-five children with decompensated SS and 24 children with early SS were enrolled. Serum cortisol and ACTH levels were determined on admission and days 3 and 8 after admission. Twenty-five healthy children were used as the control group. The children with decompensated SS were further divided into death group (n=5) and survival group (n=20) based on their clinical outcome.

RESULTSOn admission, the decompensated SS and early SS groups had significantly higher serum cortisol and ACTH levels than the control group (P<0.05), and the decompensated SS group had significantly higher serum cortisol and ACTH levels than the early SS group. On day 3 after admission, the decompensated SS group had significantly higher serum cortisol and ACTH levels than the early SS and control groups (P<0.05), and the early SS group had a significantly higher serum ACTH level than the control group (P<0.05). Among the children with decompensated SS, the death group had significantly higher serum cortisol and ACTH levels than the survival group on admission (P<0.01); on day 3 after admission, the death group still had a significantly higher serum cortisol level than the survival group (P<0.01).

CONCLUSIONSChildren with SS have increased serum cortisol and ACTH levels, which are associated with the disease severity. A persistent high serum cortisol level indicates a poor prognosis. Dynamic monitoring of serum cortisol and ACTH levels in children with SS is of great significance in evaluating the disease severity and prognosis.

Adrenocorticotropic Hormone ; blood ; Child, Preschool ; Female ; Humans ; Hydrocortisone ; blood ; Infant ; Male ; Shock, Septic ; blood ; mortality

Objective To investigate and analyze the prevalence, patterns and associated factors of domestic violence against married women in Wenzhou area. Methods a total of 705 married women took part in this cross-sectional study conducted in 2018. Conflict Tactics Scales and several short demographic questions were used in this study to collect basic information and the occurence of domestic violence within 12 months. Results Nearly 40% of married women experienced at least one incident of domestic violence during the past 12 months. 33.8% of respondents experiencing one episode of psychological violence in the past 12 months, followed by 19.5% experienced physical violence and 14.9%of sexual violence. The joint occurrence of multiple forms of violence was the most commonly reported features experiencing domestic violence. Some individual (education and Hukou), marital relationship (marital satisfaction, duration of marriage, marital autonomy marital models) and family (family model and sex roles) factors of the respondents, were negatively or positively associated with domestic violence against married women. Conclusion The results indicated that there was a high rate of domestic violence among married women in Wenzhou area. Accordingly, there is an obvious need of intervention and treatment activities to prevent and reduce the occurrence of domestic violence among the married women.

BACKGROUNDThe prevalence of sudden sensorineural hearing loss in children (CSSNHL) is consistently increasing. However, the pathology and prognosis of CSSNHL are still poorly understood. This retrospective study evaluated clinical characteristics and possible associated factors of CSSNHL.

METHODSOne hundred and thirty-six CSSNHL patients treated in Department of Otolaryngology-Head and Neck Surgery and Institute of Otolaryngology at Chinese PLA General Hospital between July 2008 and August 2015 were included in this study. These patients were analyzed for clinical characteristics, audiological characteristics, laboratory examinations, and prognostic factors.

RESULTSAmong the 136 patients (151 ears), 121 patients (121 ears, 80.1%) were diagnosed with unilaterally CSSNHL, and 15 patients (30 ears, 19.9%) with bilateral CSSNHL. The complete recovery rate of CSSNHL was 9.3%, and the overall recovery rate was 37.7%. We found that initial degree of hearing loss, onset of treatment, tinnitus, the ascending type audiogram, gender, side of hearing loss, the recorded auditory brainstem response (ABR), and distortion product otoacoustic emissions (DPOAEs) had prognostic significance. Age, ear fullness, and vertigo had no significant correlation with recovery. Furthermore, the relevant blood tests showed 30.8% of the children had abnormal white blood cell (WBC) counts, 22.1% had elevated homocysteine levels, 65.8% had high alkaline phosphatase (ALP), 33.8% had high IgE antibody levels, and 86.1% had positive cytomegalovirus (CMV) IgG antibodies.

CONCLUSIONSCSSNHL commonly occurs unilaterally and results in severe hearing loss. Initial severe hearing loss and bilateral hearing loss are negative prognostic factors for hearing recovery, while positive prognostic factors include tinnitus, gender, the ascending type audiogram, early treatment, identifiable ABR waves, and DPOAEs. Age, vertigo, and ear fullness are not correlated with the recovery. Some serologic indicators, including the level of WBC, platelet, homocysteine, ALP, positive CMV IgG antibody, fibrinogen, and some immunologic indicators, are closely related to CSSNHL.

Adolescent ; Child ; Child, Preschool ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Loss, Sensorineural ; blood ; etiology ; physiopathology ; Humans ; Male ; Otoacoustic Emissions, Spontaneous ; Retrospective Studies

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofission-associated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of pan-inhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

OBJECTIVETo investigate the safety and therapeutic effect of low dose (1000 U/m(2)) L-asparaginase (L-Asp) in the treatment of children with acute lymphoblastic leukemia (ALL).

METHODSSix patients were treated with low dose L-Asp after previously suffered severe side effects from standard dose L-Asp (5000 - 10,000 U/m(2)). Twenty-eight blood samples were obtained randomly from 5 of them. Plasma asparagine concentration was detected by reverse phase-high performance liquid chromatography (RP-HPLC).

RESULTSAll the patients treated with low dose L-Asp showed no any toxic symptoms. The plasma asparagine levels in the patients were all above 5 micromol/L except case 4 (4.91 micromol/L) before receiving L-Asp, and were all decreased below 0.5 micromol/L five days after receiving low dose L-Asp, except case 3 (3.70 micromol/L), the results being like that of receiving standard dose L-Asp.

CONCLUSIONLow dose L-Asp has definite efficacy for childhood ALL, while avoids serious side effects from standard dose L-Asp.

Adolescent ; Antineoplastic Agents ; administration & dosage ; adverse effects ; blood ; Asparaginase ; administration & dosage ; adverse effects ; blood ; Child ; Child, Preschool ; Female ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Treatment Outcome

Aim To analyze the main components of effective fractions of Inula cappa in rat plasma with UHPLC/Q-TOF/MS technology and serum pharmacochemistry theory.Methods After gavage administration with Inula cappa extracts,blood was collected from abdominal aorta,and the protein in plasma sample was precipitated by methanol.Eclipse Plus C18 RRHD (2.1 mm × 100 mm,1.8 μm) was used,with 0.1％ formic acid agueous solution (A)-0.1％ formic acid and acetonitrile (B) as the mobile phase for gradient elution,and the flow rate was 0.3 mL ·min-1 Detected at negative ion mode,and with the help of Metabolite Tools software from Bruker Corporation,components in plasma were defined.Results A total of 16 compounds were identified,including 9 prototypes and 7 metabolites.Main metabolites were isomerization,methylation,glucuronidation and recombination of caffeoylquinic acid.Conclusions Therefore,our study has comprehensively expounded Inula cappa extracts' constituents migrating to rat plasma,and provided a reference for further studies for in vivo metabolic process and effective material base of Inula cappa.

OBJECTIVESevere acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in November 2002. The SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent, but the pathology and pathogenesis are still not quite clear.

METHODSPost-mortem lung samples from six patients who died from SARS from April to July 2003 were studied by light and electron microscopy, Masson trichromal staining and immunohistochemistry. Evidence of infection with the SARS-CoV was determined by reverse-transcription PCR (RT-PCR) , serological examination and electron microscopy.

RESULTSFour of six patients had serological and RT-PCR evidence of recent infection of SARS-CoV. Morphologic changes are summarized as follows: (1) Diffuse and bilateral lung consolidation was seen in all patients (6/6) with increasing lung weight. (2) Diffuse alveolar damage was universal (6/6) with hyaline membrane formation (6/6), intra-alveolar edema/hemorrhage (6/6), fibrin deposition (6/6), pneumocyte desquamation (6/6). A marked disruption in the integrity of the alveolar epithelium was confirmed by immunostaining for the epithelial marker AE1/AE3 (6/6). (3) Type II pneumocytes, with mild hyperplasia, atypia, cytomegaly with granular amphophilic cytoplasm and intracytoplasmic lipid accumulation (5/6). (4) Giant cells in the alveoli were seen in five of 6 patients (5/6) , most of which were positive for the epithelial marker AE1/AE3 (5/6), but some cells were positive for the macrophage marker CD68(2/6). (5) A pronounced increase of macrophages were seen in the alveoli and the interstitium of the lung (6/6), which was confirmed by histological study and immunohistochemistry. (6) Haemophagocytosis was present in five of the 6 patients(5/6). (7) Lung fibrosis was seen in five patients(5/6), with alveolar septa and interstitium thickening(5/6), intraalveolar organizing exudates (6/6) and pleura thickening (4/6). Proliferation of collagen was confirmed by Masson trichromal staining, most of which was type III collagen by immunostaining. The formation of distinctive fibroblast/myofibroblast foci was seen in five patients (5/6) by light microscopy and immunochemistry. (8) Squamous metaplasia of bronchial mucosa was seen in five patients(5/6). (9) Thrombi was seen in all patients(6/6). (10) Accompanying infection was present in two patients, one was bacteria, the other was fungus. In addition, electron microscopy revealed viral particles in the cytoplasm of alveolar epithelial cells and endothelial cells corresponding to coronavirus.

CONCLUSIONDirect injury of SARS-CoV on alveolar epithelium, prominent macrophage infiltration and distinctive fibroblast/myofibroblast proliferation may play major roles in the pathogenesis of SARS.

Adult ; Antibodies, Monoclonal ; metabolism ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Epithelium ; pathology ; Female ; Humans ; Keratins ; immunology ; Lung ; pathology ; ultrastructure ; virology ; Male ; Middle Aged ; Pulmonary Alveoli ; pathology ; Pulmonary Fibrosis ; etiology ; pathology ; SARS Virus ; isolation & purification ; Severe Acute Respiratory Syndrome ; complications ; metabolism ; pathology ; virology