Adolescent ; Adult ; Cholesteatoma, Middle Ear ; complications ; congenital ; Ear, Middle ; abnormalities ; Female ; Humans ; Young Adult

Objective To report four patients with secondary α-dystroglycanopathy caused by guanosine diphosphate-mannose pyrophosphorylase-B ( GMPPB ) gene mutations and review the literature aiming to analyze the clinical manifestations , muscle image , molecular pathology and genetic characteristics of the disease.Methods The medical history , physical examination , electromyography and other clinical data of four patients with secondary α-dystroglycanopathy from two families were collected and retrospectively reviewed from 2009 to 2017.Case 1 ( proband of pedigree 1) and case 2 ( proband of pedigree 2) were then further analyzed with muscle imaging , muscle pathology and targeted next generation gene sequencing (NGS).Results Four patients came from two families (three from the same pedigree), two males and two females, with an onset age of 17 -18 years.All four cases presented as limb-girdle muscular dystrophy (LGMD) overlapping with congenital myasthenic syndrome (CMS) characterized by evident proximal limb weakness in early adulthood and fluctuating muscle weakness .They all had delayed motor milestone and did not perform well in physical education since childhood . Serum creatine kinase was elevated markedly (1877-5275 U/L).Myogenic changes on electromyography and marked attenuation on three Hz repetitive nerve stimulation were observed in all patients .Muscle MRI showed prominent involvement of bilateral hamstrings in case 1 and case 2.Muscular dystrophic patterns were demonstrated on muscle biopsies . Targeted NGS revealed two compound heterozygous missense mutations in GMPPB for each case .Case 1 carried c.860G>T (p.R287L)/c851T>C (p.V284L).Case 2 and his two affected sisters (case 3 and case 4) carried c.1097A >G ( p.N366S)/c.589G >T ( p.V197F) .All of these mutations were novel variants and pedigree analysis suggested that the two mutations were from parents .Compared with normal controls, immunohistochemistry and Western blotting showed significantly decreased expression of α-dystroglycan in the muscle tissue from case 1 and case 2.The myasthenic symptoms of all four patients were improved to varying degrees after treatment with pyridostigmine bromide . Conclusions Mutations in GMPPB can lead to dysfunction both in muscle and in neuromuscular transmission causing overlapping between LGMD and CMS phenotypes . Cholinesterase inhibitors can partly improve the symptoms of myasthenia in such patients .

AIM: To compare the safety and efficacy of conjunctival autograft transplant ( CAT ) and limbal - conjunctival autograft transplant (LCAT) for primary pterygium.
METHODS: In this prospective, randomized and controlled clinical study, 120 patients ( 120 eyes ) diagnosed with primary pterygium were collected in NO. 474 Hospital of Chinese PLA from January 2014 to January 2015. The 120 patients enrolled in the study in turn, and divided into two group by the odd and even number. The odd number underwent CAT and the even number underwent LCAT.
RESULTS:One hundred and seven patients (107 eyes) completed the follow-up of 1a, including 54 patients (54 eyes) from the CAT group and 53 patients (53 eyes) from the LCAT group. Four patients (4 eyes, recurrence rate 7. 4%) in the CAT group and 2 patients ( 2 eyes, recurrence rate 3. 8%) in the LCAT group developed recurrence. However, there were no significant in recurrence rate between CAT group and LCAT group (P =0. 678).
CONCLUSION: CAT and LCAT might be both effective treatment for primary pterygium for reducing the recurrence rate of pterygium. However, LCAT is the optimal surgical method for primary pterygium.

Objective To investigate the relationship between single nucleotide polymorphism (SNP) of BARD 1 gene and BRCA1 gene in epithelial ovarian cancer (EOC).Methods Nineteen EOC patients with BRCA1 gene mutation and 50 EOC cases without BRCA1 gene mutation between January 2016 and October 2016 were collected,and all EOC were diagnosed by pathological method.BARD1 gene variants were detected by next generation sequencing (NGS).The SNP of BARD1 gene was analyzed by Pearson linear correlation.Logistic regression analysis was used to research the clinicopathologic features and BRCA1 gene mutation associated with BARD1 gene SNP.Pearson's chi-square test was used to analyze the association between BARD1 gene Val507Met,Arg378Ser and Pro24Ser with different clinicopathologic features and BRCA1 gene mutation risk.Results (1) Eight BARD1 gene variants were found in 69 ovarian cancer patients,in which Val507Met,Arg378Ser and Pro24Ser were common variants,and the rate of mutation were all 54％ (37/69).(2) There was a significant linear correlation among Val507Met,Arg378Ser and Pro24Ser (all P＜0.01).(3) Obvious differences were found in Val507Met,Arg378Ser and Pro24Ser of BARD1 gene between BRCA1+ and BRCA1 (all P＜0.05).(4) No differences were found between BARD1 gene Val507Met,Arg378Ser and Pro24Ser and the clinicopathologic features (all P＞0.05),while obvious differences were found in BRCA1 gene mutation compared to the controls group.The risk of BRCA1 mutation in Val507Met and Arg378Ser were more evident in subjects with negative family history,positive menopause history,negative tubal ligation,onset age (≤60 years old) and sensitivity to platinum-based chemotherapy in EOC (all P＜0.05),while Pro24Ser was only more evident in positive menopause history of EOC (P＜0.05).Conclusions BARD1 Val507Met,Arg378Ser and Pro24Ser are the common genotypes,which are associated with BRCA1 mutation in EOC.The family history,menopause history,tubal ligation,onset age and sensitivity to platinum-based chemotherapy have effects on BARD1 SNP in the risk of BRCA1 gene mutation.

Objective Combination of nanoparticle with p53 and Rb gene therapy by gene targeting was applied to investigate its curative effect and safety evaluation on colorectal rabbit hepatic VX2 metastasis for tumor eradication and survival enhancement. Methods Recombinant expressing plasmids harboring wild type p53 and Rb were cotransferred or transferred separately to the rabbit hepatic VX2 metastasis by the emulsion of PLL-nHAP nanoplex and lipodiol through the hepatic artery in a tumor target manner. Subsequent co-expressions of p53 and Rb protein within the treated tumors were detected by Western blot and in situ analysis of confocal laser scanning microscope. The therapeutic effect was evaluated by the tumor growth velocity and the survival time of animals. Eventually, investigations of liver function were applied to evaluate the safety of the process. Results With safe procedure for the rabbits liver function, both p53 and Rb local nano-therapy showed favorable anti-tumor effects and increased animal survival time. p53+Rb local nano-therapy could significantly inhibit hepatic VX2 metastasis and enhance the animal survival time compared with p53 local nano-therapy or Rb local nano-therapy. Local nano-therapy showed no significant influence to animal liver function. Conclusions Rb can work synergistically with p53 in the combined therapy mediated by PLL-nHAP nanoplex to augment the anti-tumor effect. The local nano-therapy with p53 and Rb is likely to be an effective and safe anti-tumor therapy for hepatic colorectal metastasis.

Objective To investigate radiological features of patients with heroin spongiform leukoencephalopathy(HSLE)of different clinical stages and discuss the evolutional characteristics of the disease.Methods Thirty two patients with HSLE underwent precontrast MRI and postcontrast MRI.The history of addiction,clinical presentations,and brain MRI were analyzed and summarized according to the patient's clinical staging.There are 6 cases in Ⅰ stage,21 cases in Ⅱ stage,5 cases in Ⅲ stage.Results All patients had history of heroin vapor inhalation.Most of the cases developed subacute cerebellar impairment in earlier period.Brain MRI revealed symmetrical lesion within bilateral cerebellum in all patients.Splenium of the corpus callosum,posterior limb of the internal capsule,deep white matter of the occipital and parietal lobes,were gradually involved with progressive deterioration of HSLE.The brain stem and deep white matter of the frontal and temporal lobes were involved in some cases.Conclusions The history of heated heroin vapor inhalation was the prerequisite for the diagnosis of HSLE.Brain MRI presented the characteristic lesion and its evolution of HSLE.Brain MRI was very important for accurate diagnosis and helpful to judge the clinical stages according to the involved brain region.

The potential of Rhizobium sp. N613 to produce the exopolysaccharide (REPS) was studied in this paper. Using an orthogonal design in a flask-shaker culture system, the fermentation medium and conditions of synthesizing REPS were optimized. Based on these results, the fermentation kinetic parameters were obtained in the batch fermentation with a 10L fermentor. The REPS yield of 11.31g/L was achieved by metabolic regulation during 40 h fed-batch fermentation. Transplanted tumor models of sarcoma 180 in mice were used to evaluate the anti-tumor effect. The result of anti-tumor activities showed that inhibition rate was 53.40%, when dose of REPS was 5mg/kg. These results indicate that REPS has the following properties: the short duration of fermentation, the high yield, the low cost, the effective immunocompetence and thickening. Thus, REPS has the value of development and application.

OBJECTIVETo develop a three-dimensional porous film of human hair keratin (HHK)-collagen sponge complex for use as a dermal substitute.

METHODSThe three components F, B, and Z derived from healthy human hair were weaved into a meshwork and integrated with purified soluble type I collagen extracted from bovine tendons to prepare a highly porous film with vacuum freeze-drying followed by secondary cross-linking with glutaraldehyde. The film was grafted beneath the dorsal skin in 21 SD rats (experimental group), with simple collagen sponge serving as the negative control. The rats receiving surgical operation but without graft served as the blank control. The graft and its surrounding tissue were harvested on days 3, 7 and at weeks 2, 4, 6, 8, 12 after implantation for evaluation of tissue compatibility, vascularization and degradation.

RESULTSThe prepared collagen sponge film was semitransparent and porous. Three to 7 days after grafting, inflammatory reaction was relieved gradually, and several fibroblasts and blood vessels were found adherent to the grafts in the experimental groups. At week 4, the wounds healed in the experimental groups, and the fibroblasts were actively secreting collagen and the film degraded obviously with the appearance of elastic fibers. At weeks 6 and 8, new collagen fibers thickened and assumed regular arrangement, and the collagen sponge films disappeared completely. In the control groups, the changes were less obvious and total HHK degradation occurred till week 12.

CONCLUSIONThe degradable and absorbable HHK-collagen sponge film has relatively satisfactory tissue compatibility and can accelerate wound healing by stimulating cell proliferation and vascularization, showing the potential as an optimal dermal substitute.

Animals ; Collagen Type I ; chemistry ; Dermatologic Surgical Procedures ; Hair ; chemistry ; Humans ; Implants, Experimental ; Keratins, Hair-Specific ; chemistry ; Porifera ; Rats ; Rats, Sprague-Dawley ; Skin ; injuries ; Skin, Artificial ; Tissue Engineering ; methods ; Wound Healing

OBJECTIVETo investigate the relationship between sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) of rabbit with chronic myocardial infarction (MI).

METHODSThirty rabbits were randomly assigned into two groups: MI group (n = 20): ligation of the anterior descending coronary; sham operation (SO) group (n = 10): without contrary ligation. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, during sympathetic nerve stimulation, TDR change (DeltaTDR) during sympathetic nerve stimulation and ventricular fibrillation threshold (VFT) were measured at the IBZ in MI group and corresponding zone in SO group. The distribution and densities of growth associated protein 43 (GAP43) and tyrosine hydroxylase (TH) positive nerves in ventricle were also detected with immunohistochemical techniques.

RESULTSEighteen rabbits in the MI group and 10 in the SO group survived to the end of the study. The densities of GAP43 and TH at the IBZ in the MI group were significantly higher than that at the corresponding zone in the SO group (both P < 0.05). The densities of GAP43 and TH in MI rabbits positively correlated with TDR at baseline, TDR or DeltaTDR during sympathetic nerve stimulation (all P < 0.01) and both showed a weak negative correlation with VFT (r =-0.44, P = 0.07; r = -0.41, P = 0.09, respectively).

CONCLUSIONSympathetic remodeling is correlated with electrical remodeling at the IBZ in rabbits with chronic MI.

Action Potentials ; Animals ; Humans ; Male ; Myocardial Infarction ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Sympathetic Nervous System ; physiopathology

OBJECTIVETo investigate the effects of Er Xian Decoction (EXD) and its three subdivisions "warming Shen" ,"nourshing Yin" and "adjusting Chong and Ren" in regulating the level of estradiol (E2) on the primary cultured granulosa cells.

METHODSEffect of EXD and its three subdivisions, also part of the effective components of this formula, icariin and curculigoside, on level of E2 were carried out using primary cultural granulose cell as the experimental model.

RESULTEXD and its three subdivisions could stimulate the secretion of E2, especially the "warming Shen" group (P <0.05). All the composing of Chinese herbs of this formula could promote the level of E2 in different degree, and the Rhizoma Curculiginis, Radix Moromade Officinalis, and Herba Epimedii have the best effects (P <0. 01).

CONCLUSIONThe regulation of EXD on the hypothalamus-pituitary-gonad (HPG) axis may be related to promoting the secreting of E2 at the site of granulosa cell. The "warming Shen" subdivision has the better effect in promoting the secretion of E2.

Animals ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Estradiol ; metabolism ; Female ; Granulosa Cells ; drug effects ; metabolism ; Humans ; Rats