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    20 March 2019, Volume 34 Issue 3
    Diagnosis and treatment of rare diseases in China
    Zhang Songyun
    2019, 34(3):  197-200.  doi:10.3969/j.issn.1004-583X.2019.03.001
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    Rare diseases refer to a type of disease with a very low incidence rate.  At present,there are more than 7 000 kinds of rare diseases, 80% of which  are hereditary,  mainly including congenital malformations,  endocrin  metabolism, and nervous system diseases. The awareness of rare diseases is low,  the rate of misdiagnosis is high,  and the accessibility of treatment is poor. With the development of genetic technology,  great progress has been made in the diagnosis and treatment of rare diseases. Under the active promotion of the government and various social forces,  China has become the country with the fastest progress in the diagnosis and treatment of rare diseases,  which marks the improvement of medical level and the progress of social civilization in China.
    Progress in diagnosis and treatment of rare diseases from the perspective of heredity
    Wang Wei
    2019, 34(3):  201-206.  doi:10.3969/j.issn.1004-583X.2019.03.002
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    Rare diseases, also known as “orphan diseases”,  are difficult to diagnose and treat because of the extremely  low incidence of single diseases and scattered cases. About 80% of rare diseases are caused by genetic defects. Accurate diagnosis and treatment of rare diseasedependent gene levels, and research on rare diseases from a genetic perspective are  the focus of current medical research. This article reviews the general situation of rare diseases, gene diagnosis technology of rare diseases, gene therapy, preimplantation genetic diagnosis/screening technology, prenatal diagnosis, neonatal screening and so on,  aiming to show the progress of diagnosis and treatment of rare diseases from the perspective of heredity.
    Progress of inherited arrhythmia in children
    Feng Lin1, Zhang Xiufang2
    2019, 34(3):  207-211.  doi:10.3969/j.issn.1004-583X.2019.03.003
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    Recent and relevant research published in the field of inherited arrhymias  were reviewed, focusing on the 'channelopathies' that are associated with sudden  cardiac death (SCD) in children, including  long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome(BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT).
    Department of Neurology,  the Second Hospital of Hebei Medical University,  Shijiazhuang 050017,  China
    Dong Hui, Song Xueqin
    2019, 34(3):  212-218.  doi:10.3969/j.issn.1004-583X.2019.03.004
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    Duchenne muscular dystrophy (DMD) is an Xlinked recessive disorder caused by dystrophin gene mutations. It is characterized by progressive symmetrical skeletal muscle weakness and atrophy,  and easy to be misdiagnosed on account of hidden onset in children and various clinical manifestations,  including motor and nonmotor symptoms. Progress in the development of DMD gene therapy has been well made over the past 20 years. Numerous of researches are focused on exon skipping,  nonsense readthrough,  adenoassociated virusmediated micro/mini dystrophin gene delivery and gene editing using the CRISPR/Cas9 system. These innovative therapies are becoming the best means to treat DMD.
    Diagnosis and treatment of rare diseases of endocrine metabolism
    Gao Ming, Zhang Songyun
    2019, 34(3):  219-224.  doi:10.3969/j.issn.1004-583X.2019.03.005
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    The endocrine metabolic system includes endocrine glands and endocrine tissues that regulate body function by secreting hormones. The progress of endocrine rare diseases is concealed,  and the clinical manifestations overlap with common diseases. Many of them are genetic diseases, and the diagnosis depends on genetic testing. The conventional treatment is not effective. According to the first rare disease catalogue  issued  in China in 2018 and the endocrine organs mainly involved, we select typical endocrine rare diseases such as Kallmann syndrome,  type B insulin resistance and hypophosphatemic rickets for further investigation. With respect to  pituitary,  pancreatic and bone metabolism,  the pathogenesis,  clinical features,  treatment methods of endocrine rare diseases are systematically elaborated.

    Individualized treatment strategies under precision medical treatmentprogress in the treatment of pulmonary alveolar proteinosis
    Liu Xin, Duan Zheng
    2019, 34(3):  225-230.  doi:10.3969/j.issn.1004-583X.2019.03.006
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    Pulmonary alveolar proteinosis is a rare clinical syndrome, which was first reported by Rosen in 1958. It is characterized by the accumulation of phospholipidrich proteins(PAP)  that are positive forpositivperiodic acidSchiffstaining in the alveolar and bronchial lumens, leading to pulmonary ventilatory dysfunction. It was divided into three types: autoimmune PAP, congenital PAP and secondary PAP. Wholelung lavages is still the cornerstone of treatment, and GMCSF therapy, rituximab, plasma exchange and lung transplantation are emerging treatments. Most studies are in case series, often with limited patient numbers, so the level of evidence is low. Specific treatment should be classified according to different etiological factors, different treatment schemes should be chosen, and individual treatment should be carried out.
    Value of lipid accumulation product in  screening of metabolic syndrome in middleaged and elderly people
    Luo Lan, Niu Min, Zhang Nan, Gao Zhengnan
    2019, 34(3):  231-236.  doi:10.3969/j.issn.1004-583X.2019.03.007
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    Objective  To explore the value of lipid accumulation product in the screening of metabolic syndrome(MS) in middleaged and old people. Methods  Selected Dalian community residents aged over 40 years who participated in the REACTION study initiated by Chinese Medical Association from July to December 2011. According to the lipid accumulation product quartile level,male and female subjects were respectively divided into q1,  q2,  q3 and q4 and Q1,  Q2,  Q3 and Q4 groups and compared the prevalence of metabolic syndrome between groups. The optimal lipid accumulation product cut points for metabolic syndrome screening in males and females in Dalian area were determined by the analysis of working characteristic curve of the subjects.Results  ①Male and female subjects with the metabolic syndrome,  a total of 825 and 1 834 cases, at a prevalence rate of 30.02% and 25.12%,  the metabolic syndrome prevalence rates of lipid accumulation productquartile q1 and q2,  q3 and q4 groups of metabolic syndrome  respectively were 5.1%,  14.8%,  30.3% and 69.9%. Q1 and Q2,  Q3 and Q4 groups of metabolic syndromerespectively were 2.4%,  8.6%,  25.5% and 64.0%,  the differences between the groups were statistically significant (P<0.001). ②The Spearman correlation analysis showed that in the male subjects,  lipid accumulation product and DBP (r=0.145),  SBP (r=0.102),  TG(r=0.931),  fasting blood glucose (r=0.169),  postprandial 2 hours blood glucose (r=0.155) and BMI (r=0.395) were positively correlated,  and HDLc (r=0.299) was  negative correlation. In female subjects, lipid accumulation product and DBP (r=0.196),  SBP (r=0.248),  TG (r=0.908),  fasting blood glucose (r=0.269),  postprandial 2 hours blood glucose (r=0.299) and BMI (r=0.427) were positively correlated,  and HDLc (r=0.376)  was negative correlation,  P values were all less than 0.01. ③ROC curve analysis showed that among male subjects,  the area under the curve of lipid accumulation product,  BMI and waist circumference diagnosis metabolic syndrome was 0.830,  0.769 and 0.701,  respectively. Among female subjects,  the area under the curve of lipid accumulation product,  BMI and waist circumference diagnosis metabolic syndrome was 0.860,  0.791 and 0.718 respectively. Among males,  lipid accumulation product=47.45 was the optimal cut point for metabolic syndrome,  with sensitivity of  0.743   and specificity of  0.793. Among females,  lipid accumulation product=48.08 was the optimal cut point for metabolic syndrome,  with sensitivity of 0.803 and specificity of  0.762.Conclusion  Lipid accumulation product can be a reliable indicator for metabolic syndrome screening of middleaged and elderly people in Dalian area.
    Treatment of advanced squamous nonsmall cell lung cancer with programmed cell death ligand 1  inhibitors: a report of two cases and literature review
    Mo Yijun1, Zhang Jianhua1, Yan Jun1, Lin Lina2
    2019, 34(3):  237-243.  doi:10.3969/j.issn.1004-583X.2019.03.008
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    Objective  Tumor immunotherapy targeting programmed cell death ligand 1(PD1) receptor signal pathway has achieved a remarkableclinical outcomes on multiple types of tumors including nonsmall cell lung cancer(NSCLC). The study was to evaluate firstline therapy of two main PD1 inhibitors, pembrolizumab and nivolumab, with regard to activity and feasibility in advanced NSCLC in China. Methods  Two patients with advanced squamous NSCLC who had not received treatment previously were treated with intravenous pembrolizumab (100 mg every 3 weeks),  or nivolumab (2  mg/kg every 2 weeks),  respectively. Tumor response was assessed by RECIST v1.1 every one or two periods. Results  After treatment for 2 periods,  both patients experienced partial response (PR) of lung cancer,  and respiratory symptoms improved significantly and inflammation relieved. But unfortunately the patient treated with pembrolizum was observed brain metastates and finally died of the progressive brain metastases when assigning the 3rd treatment. The other patient treated with nivolumab was observed stable and obvious improvement of lung caner with PR,  but multiple brain metastases when assigned the 4th therapy which increased slightly when assigned the 5th treatment with stable disease (SD). During the immunotherapy,  the blood concentration of CA125 decreased significantly and no adverse reactions were observed in both patients. Conclusion  Preliminary studies have shown significant efficacy and safety by treatment with PD1 inhibitors in advanced primary NSCLC,and blood concentration of CA125 may be considered as an index of outcome. However,  PD1 inhibitors could not relieve the progression of brain metastases. And this conclusion needs to be verified by enrolling more patients and further study.
    Analysis of visual function impairment in patients with neuromyelitis optica spectrum disorders
    Liu Zhiyana, Ge Zhaominga, Wu Chuangb, Du Ningc
    2019, 34(3):  244-247.  doi:10.3969/j.issn.1004-583X.2019.03.009
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    Objective  To investigate the characteristics of impairmentto visual function  viameasuring the length of damagedvisual pathway by enhanced magnetic resonance imaging(MRI) of optic nerve and detect the thickness of retinal nerve fiber layer(RNFL) and the ganglion cell complex(GCC) by optic coherence tomography(OCT) in patients with neuromyelitis optica spectrum disorders(NMOSD) and multiple sclerosis(MS).  Methods  70 patients with NMOSD, 40 patients with MS and 70 healthy people in the Department of Neurology, Second Hospital of Lanzhou Universitywere retrospectively collected. TThe visual enhancement of MRI was used to observe the enhancement features of the pathological lesions and to measure the length of the lesions; the thicknessof RNFL (including the average and superior, inferior, nasal and temporal) and GCC (including the average and superior, inferior) were measured by OCT and compared. Results  Compared with the MS group, the enhancement of visual lesions in NMOSD group was significantly increased, optic chiasm and optic tract were more easily involved, and the length of lesions was significantly increased (P<0.01).  The thickness of RNFL and GCC in NMOSD group and MS group was lower than that in normal control group (P<0.01).  The RNFL and GCC thickness in the NMOSD and MS groups weresignificantly thinner thanthenormal group(P<0.01), and the thickness of RNFL and GCC in the NMOSD group was the thinnest (P<0.01). Conclusion   The impairment of visualpathway inthe NMOSD group involvingthe orbital segment and the suprachiasmatic segment was more extensiveand serious than intheMS group.

    Clinical analysis of rheumatoid arthritis complicated with popliteal cyst
    Wang Zengzeng, XU Ting, WU Min
    2019, 34(3):  248-252.  doi:10.3969/j.issn.1004-583X.2019.03.010
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    Objective  To analyze the clinical characteristics and prognosis of rheumatoid arthritis (RA) with popliteal cysts.Methods  General condition, clinical manifestations, laboratory tests,treatment and prognosis of 62 patients with RA with popliteal cysts admitted to the Department of Rheumatology and Immunology, Changzhou First People's Hospital from 2010 to 2018were collected, 50 patients with RA without popliteal cysts were selected as comparisons. Results  Compared with patients without popliteal cysts,patients with popliteal cystshad a longer duration (P=0.040), the proportion of patients with RA in activity, knee joint involvement increased significantly, the proportion of firstinfested joints in the knee joint increased significantly ,the proportion of people with limited mobility increased significantly (P<0.05). Of the 62 patients, 12 had a ruptured popliteal cyst and 50 had no rupture of the popliteal cyst. Compared with patients with unruptured popliteal cysts, the proportion of patients with ruptured axillary cysts aged ≥65 years old  increased (P=0.040), the proportion of cysts ≥16 cm2 increased (P=0.043) ,  the proportion of Rauschning and Lindgren  Ⅲ  patients increased (P=0.046),  the proportion of patients with reduced knee pain and swelling at admission was significantly higher than that without ruptured(P=0.000). Logistic multivariate regression analysis showed that DAS28 score, the total duration of the disease, the first joint affected was the knee joint, and the number of systemic damage ≥3 werethe risk factors for the occurrence of popliteal cyst in patients with RA. The treatment of RA with popliteal cysts included drug therapy and drug combined with joint cavity puncture. Patients treated with drugs combined with joint cavity puncture hada faster onset than patients treated with drugs alone.Symptoms of swelling and pain in the calf wererelieved faster (P=0.000).The cure rate and recurrence rate of the two regimens were not statistically significant (P>0.999).Conclusion  The longer the course of disease of RA patients, the more obvious the disease activity, the more serious the system damage,the moreprone to popliteal cysts;the larger the cyst, the greater the risk of rupture.Drug combined with joint cavity puncturetreatment has a shorter onset time, symptoms are relieved faster.
    Effects of high-flux hemodialysis combined with L-carnitine treatment on lipid metabolism in  uremic patients
    Huang Junyue, Ma Zhigang, Li Yingping, Xue Rong, Huang Wenhui, Jing Xiaojiang
    2019, 34(3):  253-256.  doi:10.3969/j.issn.1004-583X.2019.03.011
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    Objective  To investigate the effect of high flux hemodialysis(HFHD)  combined with Lcarnitine therapy on lipid metaolism in uremic patients.Methods  Seventytwo  uremic patients were randomly divided into three groups. Group hemodialysis(HD)was treated by lowflux hemodialysis three times a week. Group HFHD was treated by  HFHD three times a week. Group HFHD+Lcarnitine was treated by HFHD three times a week,  and the patients were given Lcarnitine injection treatment at the end of each HFHD.All patients were followed up for 3 months. TC,TG,HDL,LDL,  Hb,  Alb were measured before and after the 3 months’ treatments,  then the KT/V ratio and URR was calculated. Results   TG increased in group HD before and after treatment (P<0.05). Compared to HD group,  TG decreased and Hb increased significantly in group HFHD and HFHD+Lcarnitine before and after treatment (P<0.05). However,  TG decrease and Hb increase had no significant differences between HFHD and HFHD+Lcarnitine group (P>0.05). LDL reduction is more significant in group HFHD+Lcarnitine than in group HD and HFHD (P<0.05). Conclusion  HFHD  combined with Lcarnitine  might effectively improve lipid metabolism in MHD patients.
    Analysis on 14 cases of dermatomyositis and polymyositis associated with malignancy
    Tang Ziyia, Wang Dana, Zhen Jianxionga, Zhou Wenjuna, Qin Qiana, Xiong Qinb, Yi Tinga, Zhang Quanbob, Qing Yufenga
    2019, 34(3):  257-261.  doi:10.3969/j.issn.1004-583X.2019.03.012
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    Objective  To investigate the clinical features and related factors of polymyositis(PM) and dermatomyositis(DM) combined with malignancy in order to make the early diagnosis and intervene the disease,  and  improve survival rate of PM/DM patients. Methods  The  data of 117 PM/DM patients admitted to the hospital in the past 4 years were collected and compared.Results  ①PM/DM patients with malignant tumors (14 cases) were older than those with PM/DM without malignant tumors (103 cases) (t=2.493, P<0.05)(t=2.493,P<0.05).  There was no significant difference in the incidence, sex and duration of PM and DM malignant tumors between the two groups; ②The incident of model skin rash such as Heliotrop rash,  Vshaped rash in the neck and chest area and Gottron sign in malignancy group were all higher than that of nonmalignancy group(P<0.01),and the incidence of arthritis was lower than nonmalignancy group(P<0.05); ③The elevated ESR in malignancy group was higher than nonmalignancy group(Z=-2.809,P<0.01),but  GLOB was lower than that of nonmalignancy group(Z=-2.9149,P<0.01). Conclusion  PM/DM is easy to be associated with malignancy,  which is common in elderly  patients with the model skin rash,  elevated ESR,  lower GLOB and without arthritis.Therefore,  PM/DM patients who present the above symptoms and serologic results should be screened for malignant tumors closely.
    Bilateral thalamic stroke due to occlusion of the artery of Percheron:a case report and review of literature
    Cao Cuifang, Guo Shuying, Zhai Qiongqiong, Xue Fang
    2019, 34(3):  262-266.  doi:10.3969/j.issn.1004-583X.2019.03.013
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    Objective  To review the medical record of a case of bilateral thalamic strokedue to occlusion of the artery of Percheron (AOP) and improve awareness of the disease. Methods  We analyzed the etiology, clinical features and image findings of a patient with AOP infarction in our department and reviewed all related literatures.Results  The occlusion of AOP was a rare condition that caused bilateral thalamic ischemic stroke and generated a clinical syndrome characterized by bilateral vertical gaze palsy,  memory impairment and hypersomnia. Conclusion  The incidence of  bilateral thalamic stroke due to this anatomical variant is low,  and its diagnosis can be delayed because of the wide spectrum of clinical signs.
    Metaanalysis of factors influencing recurrence after radiofrequency ablation of atrial fibrillation
    Nuozha Dainier, Muhuyati
    2019, 34(3):  267-272.  doi:10.3969/j.issn.1004-583X.2019.03.014
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    Objective  To investigate  the predictive value of duration of disease,  coronary heart disease,  diabetes mellitus,  hypertension,  left atrial dimension (LAD),  left ventricular ejection fraction (LVEF),  body mass index (BMI) for recurrence after radiofrequency ablation of persistent atrial fibrillation(AF).Methods   The analysis of all related literatures in PubMed(19952018),  CBM(19952018),  CNKI(19582018),  WanfangData(19992018),  VIP(19892018) has been made. Selection criteria were the cohort study of risk factors affecting recurrence after radiofrequency ablation in patients with atrial fibrillation. All statistical tests were performed with RevMan5.3 software. Results  A total of 17 articles and 2827 patients were included. The results indicated that the duration of atrial fibrillation(MD=2.83,95%CI[2.48,3.19],P<0.05),  BMI (MD=0.84,95%CI[0.49,1.18],P<0.05)  and left atrial dimension (MD=2.63,95%CI[2.14,3.12],P<0.05)  were all greater in the recurrence group than in the nonrecurrence group. The LVEF of  recurrence group was lower than that of  nonrecurrence group (MD=-2.14,  95%CI[-3.04, -1.25],  P<0.05). Whether the patient had coronary heart disease (OR=0.75,  95%CI[0.55,  1.03],  P>0.05),  diabetes  (OR=1.15,  95%CI[0.86,  1.53],  P>0.05),  hypertension  (OR=1.07,  95%CI[0.75, 1.54], P>0.05)   had no relationship with recurrence after radiofrequency ablation of atrial fibrillation. Conclusion  Existing evidence shows that long course of atrial fibrillation,  high BMI,  long left atrial dimension and lower  LVEF are risk factors for recurrence after radiofrequency ablation of atrial fibrillation,  while whether patients have coronary heart disease,  diabetes and hypertension before surgery has no relationship with recurrence after radiofrequency ablation of atrial fibrillation.
    LGI1 antibodyrelated limbic encephalitis: a case report and literature review
    Sun Mei1, Hou Xiaoxia2, Jin Shanquan1, Shen Feifei1, Cheng Hong1
    2019, 34(3):  273-275.  doi:10.3969/j.issn.1004-583X.2019.03.015
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    LGI1 antibody related  limbic encephalitis is an autoimmune disease characterized by sudden cognitive,  and  emotional changes and epileptic seizures. It rarely coincides with tumor and has a better response to immunotherapy. The early diagnosis and appropriate treatment suggest a better prognosis for patients. A case of LGI1 antibody related limbic encephalitis admitted to our hospital is reported.
    Primary pulmonary synovial sarcoma: report of 2 cases and literature review
    Zhang Xuepei, Li Jianguo
    2019, 34(3):  276-279.  doi:10.3969/j.issn.1004-583X.2019.03.016
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    A retrospective study was performed in 2 cases of primary pulmonary synovial sarcoma (PPSS) with short course of the disease. Chest CT scan showed that the lung mass had the characteristics of definite boundaries, uneven density distribution, and heterogeneous  enhancement on CT  enhanced scan. Pathological examination showed the dense proliferation of spindle cells with less cytoplasm, higher nucleoplasmic ratio, fine chromatin, inconspicuous nucleoli, and mitotic figure. Immunohistochemistry revealed that the cells were positive for epithelial membrane antigen(EMA), vimentin, CD99 and CK, negative for CD34,  Actin,  S100 and Desmin, and partially positive for Ki67. Cytogenetics showed SS18 gene fragmentation test (FISH method) was positive. Conclusively, the diagnostic level of PPSS can be improved with the combination of  chest  CT sacn, pathological examination, immunohistochemistry and the examination of fusion gene.