简介：AbstractTargeted sequencing and whole exome sequencing are the most common approaches used to detect causative variants in Mendelian diseases; however, using DNA-based sequencing techniques, the current molecular diagnostic yield is at best 50%. In recent years, RNA sequencing has been shown to be able to provide a genetic diagnosis in patients whose conditions were previously unable to be identified by DNA analysis. RNA sequencing can reveal expression outliers, aberrant splicing events, allele-specific expression, and new pathogenic variants, and as such can complement and expand on the traditional genomic methods used to diagnose Mendelian diseases. Therefore, RNA sequencing is expected to become a routine method for genetic diagnosis in the future. This article reviews the applications and challenges of RNA sequencing in the genetic diagnosis of Mendelian diseases.

简介：AbstractObjective:The impact of dairy fat on inflammatory bowel disease remained inconclusive. We aimed to compare the effects of whole-milk and skimmed-milk consumption on the risk of inflammatory bowel disease using a Mendelian randomization analysis.Methods:We conducted a genome-wide association study of the preference for whole versus skimmed milk using data for 20,200 whole-milk consumers and 67,847 skimmed-milk consumers from the UK Biobank. The lead single nucleotide polymorphisms in the associated loci were identified at the genome-wide significance level, and were further employed as instrumental variables for whole-milk preference. We conducted a two-sample Mendelian randomization analysis with whole-milk preference as the exposure and inflammatory bowel disease as the outcome. The pleiotropic effects and heterogeneity of the instrumental variables were estimated using Mendelian randomization-Egger regression and Cochran Q test, respectively. This study was conducted using the UKB resources under the application "53536" . The UK Biobank was approved by the North West Multi-center Research Ethics Committee, the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland.Results:The genome-wide association study identified five lead nucleotide polymorphisms associated with whole-milk preference. Mendelian randomization indicated that whole-milk preference significantly decreased the risk of inflammatory bowel disease (β=-1.735, P=0.048). Of the two subtypes, whole-milk preference was associated with a lower risk of Crohn disease (β=-2.549, P=0.032), but had no significant effect on the risk of ulcerative colitis (β=-1.002, P=0.44).Conclusion:Consumption of whole-milk fat may protect against Crohn disease, compared with skimmed milk. This conclusion was based on causal inference in a cohort study, and further validation in randomized controlled trials is warranted.

简介：AbstractBackground:High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease (ESRD). IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults. Here, we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization (MR) approach.Methods:For observational analysis, 108 IgAN patients, 30 lupus nephritis (LN) patients, 50 minimal change disease (MCD) patients, and 206 healthy controls were recruited from April 2014 to April 2015. Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records. For MR analysis, we further included 1686 IgAN patients. The missense variant methylenetetrahydrofolate reductase C677T (rs1801133) was selected as an instrument, which was genotyped by TaqMan allele discrimination assays.Results:Majority of IgAN patients (93.52%, 101/108) showed elevated levels of plasma homocysteine (>10 μmol/L). Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients (median: 18.32 vs. 11.15 μmol/L, Z = －5.29, P < 0.01) and in healthy controls (median: 18.32 vs. 10.00 μmol/L, Z = －8.76, P < 0.01), but comparable with those in LN patients (median: 18.32 L vs. 14.50 μmol/L, Z = －1.32, P = 0.19). Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio (22.22% vs. 51.85% vs. 70.37% vs. 70.37%, χ2 = 14.29, P < 0.01), serum creatinine (median: 77.00 vs. 100.00 vs. 129.00 vs. 150.00 μmol/L, χ2 = 34.06, P < 0.01), estimated glomerular filtration rate (median: 100.52 vs. 74.23 vs. 52.68 vs. 42.67 mL·min－1·1.73 m－2, χ2 = 21.75, P < 0.01), systolic blood pressure (median: 120.00 vs. 120.00 vs. 125.00 vs. 130.00 mmHg, χ2 = 2.97, P = 0.05), diastolic blood pressure (median 80.00 vs. 75.00 vs. 80.00 vs. 81.00 mmHg, χ2 = 11.47, P < 0.01), and pathologic tubular atrophy and interstitial fibrosis (T) (T0/T1/T2: 62.96%/33.33%/3.70% vs. 29.63%/40.74%/29.63% vs. 24.00%/48.00%/28.00% vs. 14.81%/37.04%/48.15%, χ2 = 17.66, P < 0.01). The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12 (P < 0.01). MR estimates showed causal positive effects of homocysteine on serum creatine (β = 0.76, P = 0.02), systolic blood pressure (β = 0.26, P = 0.02), diastolic blood pressure (β = 0.20, P = 0.01), and pathologic T lesion (β = 0.01, P = 0.01) in IgAN.Conclusions:By observational and MR analyses, consistent results were observed for associations of plasma homocysteine with serum creatinine, blood pressures, and pathologic T lesion in IgAN patients.

简介：AbstractObjective:Observational studies have reported malnutrition and vitamin deficiency in patients with schizophrenia (SZ), which can lead to serious metabolic syndromes and decrease anti-psychiatric drug outcomes. Whereas, vitamin intake along with psychiatric medication can enhance the medication outcomes. However, it is still unknown if SZ induces vitamin deficiency. Herein, we conduct the Mendelian randomization analysis to explore the causal relationship between schizophrenia and vitamins supplementation.Methods:We retrieved the genome-wide summary statistical data for schizophrenia from recent SZ GWAS data (43,175 cases and 65,166 controls) and vitamins supplementation GWAS data from Neale’s GWAS datasets (more than 337,000 samples from the European population) and performed a two-sample Mendelian randomization analysis to determine the causal association of SZ with vitamin supplementation, in addition, we conduct the sensitivity analysis to obtain reliable results and remove confounding bias.Results:SZ have causal relationships with vitamins A, B, C, D, and E (SZ/vitamin A: β = 0.002, se= 0.001, 95% confidence interval (CI): 0.001 to 0.004, P= 1.41E-05, heterogeneity P= 0.4486; SZ/vitamin B: β= 0.004, se= 0.001, 95% CI: 0.002-0.005, P= 7.0E-05, heterogeneity P= 0.2217; SZ/vitamin C: β= 0.004, se= 0.001, 95% CI: 0.002-0.007, P= 0.001, heterogeneity P= 0.1349; SZ/vitamin D: β= 0.003, se= 0.001, 95% CI: 0.002-0.005, P= 0.001, heterogeneity P= 0.433; SZ/vitamin E: β= 0.003, se= 0.001, 95% CI: 0.002-0.005, P= 5.0E-05, heterogeneity P= 0.1382).Conclusion:Our findings suggest that vitamin levels and supplementation should be carefully controlled in patients with SZ, which in turn may enhance the therapeutic effects of antipsychotic drug treatments.

简介：AbstractBackground:Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).Methods:The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.Results:The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.Conclusion:Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

简介：Ltmedisease(Lymeborreliosis)iscausedbythetick-bornespiro-elraeteBorreliaburgdooCeri.Erythemamigrans,anearlyskinlesion,isthemostcommonclinicalpresentation.Theorganismmayspread,causingvariouslatermanifestations.

简介：春季是传染性疾病的高发时段，预防工作一定要做到及时、有效。也许从下面的短文中我们可以得到一些启示！

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简介：LastWednesday,AgricultureSecretaryAnnVenemanannouncedthefirstcaseofmadcowdiseaseintheUnitedStates.Atestseemedtoshowbovinespongiformencephalopathy,orB-S-E.inacowfromWashingtonstate.Thenextday,alaboratoryinWaybridge,England,Confirmed(证实）thecase。

简介：印射响应许多ligands和房间刺激涉及大量的细胞的小径和功能的家族asestransduce信号。MAPK的异常或不恰当的功能现在在从癌症到煽动性的疾病到肥胖和糖尿病的疾病被识别了。在许多房间类型，MAPKERK1/2被连接到细胞增殖。因为在地岬和B-Raf的变化，能激活ERK1/2串联，在许多人的肿瘤被发现，ERK1/2被认为在一些癌症起一个作用。发信号的反常ERK1/2也在polycystic肾疾病被发现了，并且象cardio-facio-cutaneous症候群那样的严肃的发展混乱在ERK1/2串联的部件从变化产生。ERK1/2在区分得好的房间是必要的并且在神经原并且在上皮的极性的维护被连接了到长期的potentiation。另外，ERK1/2为在胰腺的贝它房间的胰岛素基因抄写是重要的，它响应传播葡萄糖的增加生产胰岛素在有机体允许有效葡萄糖利用和存储。导致或镇压的营养素和荷尔蒙胰岛素分泌物以在贝它房间上反映能分泌的需求的一种方式激活或禁止ERK1/2。在这和另外的规章的小径的骚乱可以导致对某些人的混乱的病原学的ERK1/2的贡献。

简介：Asthmadevelopsinaboutoneadultperthousandpopulationperyear,andepidemiologicalstudiesindicatethatabout10%ofcasescanbeattributedtoexposuresatwork.However,occupationalasthmaisidentifiedlesscommonlythanthisinclinicalpractice;anincidenceof800-1000casesperyearisestimatedbytheUKSurveillanceofWork-RelatedandOccupationalRespiratoryDiseasescheme.Occupationalasthmaiseasilymissedbecause,apartfromitsassociationwithwork,

简介：HeartdiseaseistheleadingkillerofAmericans.Butitkillsmorewomenthanmen.TheAmericanHeartAssociationsaysheartdiseaseandothercardiovascular(心血管的)disorderskillaboutfivehundredthousandwomenayear.Thatismorethanthenextsevencausesofdeathcombined.

简介：AbstractBackground:The prevalence rates of freezing of gait (FOG) in Parkinson’s disease (PD) vary widely, ranging from 14.0 to 55.1%. Our aim is to calculate the overall prevalence of FOG in all PD patients with different disease durations and severities.Methods:Using Medline/PubMed/Embase, we carried out a systematic literature search for studies reporting the PD and clinically relevant FOG.Results:After primary screening, a total of 35 studies were identified and further analyzed for inclusion into the analysis, and 29 studies fulfilled the quality criteria and included in this meta-analysis. The overall prevalence of FOG in PD was 39.9% (95% CI 35.3-44.5%). The FOG identified by the freezing of gait questionnaire item 3 may be more prevalent (43.8%, 95% CI 38.5-49.1%) than the FOG identified by the Unified Parkinson’s Disease Rating Scale item 14 (36.0%, 95% CI 29.0-43.1%). Disease duration and severity are both the clinical features associated with the FOG. The highest FOG prevalence rate in PD patients was seen in patients with disease durations ≥ 10 years, at 70.8%, followed that of PD patients with disease durations ≥ 5 years (53.3%), and PD patients with disease durations < 5 years (22.4%). FOG presented in 28.4% of PD patients with Hoehn and Yahr staging (H&Y) score ≤ 2.5, and in 68.4% of PD patients with H&Y score ≥ 2.5.Conclusion:This meta-analysis confirms that the prevalence of FOG in PD is considerable, and highlights the need for accurate identification of FOG in PD.

简介：AbstractBackgroundSince early December 2019, the 2019 novel coronavirus disease (COVID-19) has caused pneumonia epidemic in Wuhan, Hubei province of China. This study aimed to investigate the factors affecting the progression of pneumonia in COVID-19 patients. Associated results will be used to evaluate the prognosis and to find the optimal treatment regimens for COVID-19 pneumonia.MethodsPatients tested positive for the COVID-19 based on nucleic acid detection were included in this study. Patients were admitted to 3 tertiary hospitals in Wuhan between December 30, 2019, and January 15, 2020. Individual data, laboratory indices, imaging characteristics, and clinical data were collected, and statistical analysis was performed. Based on clinical typing results, the patients were divided into a progression group or an improvement/stabilization group. Continuous variables were analyzed using independent samples t-test or Mann-Whitney U test. Categorical variables were analyzed using Chi-squared test or Fisher’s exact test. Logistic regression analysis was performed to explore the risk factors for disease progression.ResultsSeventy-eight patients with COVID-19-induced pneumonia met the inclusion criteria and were included in this study. Efficacy evaluation at 2 weeks after hospitalization indicated that 11 patients (14.1%) had deteriorated, and 67 patients (85.9%) had improved/stabilized. The patients in the progression group were significantly older than those in the disease improvement/stabilization group (66 [51, 70] vs. 37 [32, 41] years, U= 4.932, P= 0.001). The progression group had a significantly higher proportion of patients with a history of smoking than the improvement/stabilization group (27.3% vs. 3.0%, χ2 = 9.291, P = 0.018). For all the 78 patients, fever was the most common initial symptom, and the maximum body temperature at admission was significantly higher in the progression group than in the improvement/stabilization group (38.2 [37.8, 38.6] vs. 37.5 [37.0, 38.4]°C, U= 2.057, P= 0.027). Moreover, the proportion of patients with respiratory failure (54.5% vs. 20.9%, χ2 = 5.611, P = 0.028) and respiratory rate (34 [18, 48] vs. 24 [16, 60] breaths/min, U= 4.030, P = 0.004) were significantly higher in the progression group than in the improvement/stabilization group. C-reactive protein was significantly elevated in the progression group compared to the improvement/stabilization group (38.9 [14.3, 64.8] vs. 10.6 [1.9, 33.1] mg/L, U= 1.315, P= 0.024). Albumin was significantly lower in the progression group than in the improvement/stabilization group (36.62 ± 6.60 vs. 41.27 ± 4.55 g/L, U = 2.843, P = 0.006). Patients in the progression group were more likely to receive high-level respiratory support than in the improvement/stabilization group (χ2 = 16.01, P = 0.001). Multivariate logistic analysis indicated that age (odds ratio [OR], 8.546; 95% confidence interval [CI]: 1.628-44.864; P = 0.011), history of smoking (OR, 14.285; 95% CI: 1.577-25.000; P= 0.018), maximum body temperature at admission (OR, 8.999; 95% CI: 1.036-78.147, P= 0.046), respiratory failure (OR, 8.772, 95% CI: 1.942-40.000; P = 0.016), albumin (OR, 7.353, 95% CI: 1.098-50.000; P = 0.003), and C-reactive protein (OR, 10.530; 95% CI: 1.224-34.701, P = 0.028) were risk factors for disease progression.ConclusionsSeveral factors that led to the progression of COVID-19 pneumonia were identified, including age, history of smoking, maximum body temperature at admission, respiratory failure, albumin, and C-reactive protein. These results can be used to further enhance the ability of management of COVID-19 pneumonia.

简介：Paget'sdiseaseofboneisafocaldisorderofboneremodellingcausedbyabnormallyincreasedosteoclast-mediatedboneresorption.qtleaffectedboneschangeinshaw,sizeanddirection,whiletherestoftheskeletonremainsnormal.TheclinicalconsequencesofthediseasewerefirstdescribedbySirJanlesPagetin1876(Figure1).

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简介：Agluten-freedietiscurrentlytheonlyeffectivemeansoftreatingindividualswithceliacdisease.Suchadietenablesceliacpatientstocontroltheirsymptomsandavoidvariouscomplicationsassociatedwiththiscondition.However,whilethequalityofgluten-freefoodshassignificantlyimprovedduringrecentdecades,maintenanceofagluten-freedietdoesnotnecessarilyensureadequatenutritionalintake.Becauseoatsareanimportantsourceofproteins,lipids,vitamins,minerals,andfibre,theirinclusioninagluten-freedietmightimprovethenutritionalstatusofaceliacpatient.AlthoughoatsareincludedinthelistofglutenfreeingredientsspecifiedinEuropeanregulations,theirsafetywhenconsumedbyceliacpatientsremainsdebatable.Somestudiesclaimthatpureoatsaresafeformostceliacpeople,andcontaminationwithothercerealsourcesisthemainproblemfacingpeoplewiththisdisease.However,itisnecessarytoconsiderthatoatsincludemanyvarieties,containingvariousaminoacidsequencesandshowingdifferentimmunoreactivitiesassociatedwithtoxicprolamins.Asaresult,severalstudieshaveshownthattheimmunogenicityofoatsvariesdependingonthecultivarconsumed.Thus,itisessentialtothoroughlystudythevarietyofoatsusedinafoodingredientbeforeincludingitinagluten-freediet.

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简介：Cardiovasculardisease(CVD)isthenumberonecauseofmortalityworld-wideandplacesahighmedicalandsocioeconomicburdenondevelopingcountries.OurunderstandingofCVDanditsevolutionoverthelast100yearshasalteredconsiderably.ReasonsfortheincreasedrateofCVDinthedevelopingworldincluderapidurbanizationandthedemographicshiftknownasthemodernepidemiologictransition.ThecaseforinterventionisbasedonbothmajorhumanandeconomicimpactsofCVD.Ithasbeenestimatedthatcost-effectiveinterventionsindevelopingcountrieswithahighburdenofCVDcouldresultinaprojected24millionlivessaved.ThisreductioninCVDmortalitycouldreduceeconomiccostsby$8billion.Approachestointerventioninclude:1)cardiovascularhealthpromotionandCVDpreventionand2)actionplansadvocatedbytheWorldHealthOrganization.