Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome(NS)of different etiologies is critical for early clinical guidance.We employed whole-exome sequencing(WES)t...Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome(NS)of different etiologies is critical for early clinical guidance.We employed whole-exome sequencing(WES)to detect monogenic causes of NS in a multicenter cohort of 637 patients.In this study,a genetic cause was identified in 30.0%of the idiopathic steroid-resistant nephrotic syndrome(SRNS)patients.Other than congenital nephrotic syndrome(CNS),there were no significant differences in the incidence of monogenic diseases based on the age at manifestation.Causative mutations were detected in 39.5%of patients with focal segmental glomerulosclerosis(FSGS)and 9.2%of those with minimal change disease(MCD).In terms of the patterns in patients with different types of steroid resistance,a single gene mutation was identified in 34.8%of patients with primary resistance,2.9%with secondary resistance,and 71.4%of children with multidrug resistance.Among the various intensified immunosuppressive therapies,tacrolimus(TAC)showed the highest response rate,with 49.7%of idiopathic SRNS patients achieving complete remission.Idiopathic SRNS patients with monogenic disease showed a similar multidrug resistance pattern,and only 31.4%of patients with monogenic disease achieved a partial remission on TAC.During an average 4.1-year follow-up,21.4%of idiopathic SRNS patients with monogenic disease progressed to end-stage renal disease(ESRD).Collectively,this study provides evidence that genetic testing is necessary for presumed steroid-resistant and idiopathic SRNS patients,especially those with primary and/or multidrug resistance.展开更多
Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA...Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA”is its accessibility.In cancer cells,aberrant chromatin accessibility is recognized as one of the major hallmarks.Understanding such events requires high-throughput screening,such as Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq),which generates large-scale data that are puzzling for biologists.However,existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes.Here,we developed Shiny Pan-cancer Accessible Chromatin Explorer(SPACE)as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types.展开更多
The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The r...The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The rest of them, R334 W,R334Q, G481 D, M513 T and R587 C, have been reported previously. Among all the mutations, R334 W, R334 Q and C495 R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients.展开更多
BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify t...BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.展开更多
The distribution of hepatitis B virus genotype in Hubei province and its clinical signifi- cance were investigated. HBV genotypes of 276 patients were detected by PCR-microplate sandwich hybrization-ELISA technique. T...The distribution of hepatitis B virus genotype in Hubei province and its clinical signifi- cance were investigated. HBV genotypes of 276 patients were detected by PCR-microplate sandwich hybrization-ELISA technique. The level of HBV DNA was detected by using PCR-fluorescence quantification test. Among 276 patients, there were 78 cases of HBV asymptomatic carriers, 110 cases of chronic hepatitis B (CHB), 62 cases of severe hepatitis (SH) or liver cirrhosis (LC) and 26 cases of hepatocellular carcinoma (HCC). The genotypes of HBV included C, B, mixtures (B+C, B+D, C+D) and D, accounting for 55.8%, 25.4%, 16.7% and 2.1% respectively. The average level of HBV DNA in genotypes C, B, mixtures and D was 1.20×106, 7.81×104, 3.26×105 and 5.01×104 cop- ies/mL respectively. The ratio of SH, LC and HCC in genotype B, C and mixtures was 20%, 30% and 48% respectively. Statistical analysis revealed the percentage of genotype mixtures infection was sig- nificantly higher than that of genotype B infection. There was no significant difference in the per- centage between genotype B and genotype C or between genotype C and mixtures. The distribution of genotype B, C and mixtures in SH, LC and HCC was significantly different. The frequency of HCC was zero in patients with co-infection. Genotype D was only related with SH and LC. The in- creased ALT could be converted to categorical grades of severity. From mild, moderate to severity, the prevalence of genotype C showed an opposite trend, although no statistically significant differ- ence was observed. The HBeAg positive rate was higher in patients with genotype C infection than in those with genotype B, especially in the patients whose ages were from 31 to 40 years old. Compared with genotype B, genotype C showed a higher HBeAg positive rate in patients with SH and LC. The percentage of SH, LC and HCC was higher in patients with genotype C and mixtures infection. On the contrary, the percentage of genotype B was lower. The HBeAg positive rate in patients with genotype C infection was higher than those with genotype B infection. Genotype C and mixtures may be associated with development of severe liver disease.展开更多
Objective To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene,and to improve clinicians'unders...Objective To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene,and to improve clinicians'understanding of the ALG14 gene and its associated disorders.展开更多
Covering the entire human body, the skin is considered to be one of the most important organs, since it is the first line of protection against chemical and biological external agents. Although the skin protects tissu...Covering the entire human body, the skin is considered to be one of the most important organs, since it is the first line of protection against chemical and biological external agents. Although the skin protects tissues and organs against external aggression, it can still be unbalanced by various skin diseases, such as psoriasis. This non-contagious inflammatory dermatosis is characterized by the occurrence of erythematous lesions of various sizes covered with whitish scales. This scaling of the skin is the result of a rapid renewal of the epidermis, occurring over five to seven days instead of 28 days. Psoriasis vulgaris, or plaque psoriasis, is the most common form of this disease and is therefore commonly referred to by the term “psoriasis”. This work is a review of the literature on plaque psoriasis, aiming at a better comprehension of the pathology at the histological level, but also to understand the genetic and environmental factors associated with this inflammatory dermatosis.展开更多
Objective The occurrence characteristic of Kashin Beck Disease (KBD) in pedigrees ascertained on the basis of one proband was estimated. Methods A total of 255 individuals in 40 pedigrees were collected from areas ...Objective The occurrence characteristic of Kashin Beck Disease (KBD) in pedigrees ascertained on the basis of one proband was estimated. Methods A total of 255 individuals in 40 pedigrees were collected from areas in the Shaanxi Province. Results ① Parents and siblings of index cases have a 3-4 times higher risk than a random unrelated individual. The odds ratio for disease is higher in mothers than in fathers of index cases; ② Prevalence in relatives of index cases (K r= 59.2% ) greatly exceeds population prevalence (K= 17.5% ); ③ K r increases with sibship size; ④ There is no significant difference of K r for male and female siblings of index cases. Also, population prevalence is not sex specific. Conclusion In conjunction with environmental agents, genetics may play an important role in KBD etiology.展开更多
Tropical calcific pancreatitis(TCP)is a form of chronic non-alcoholic pancreatitis initially reported in the developing parts of the tropical world.The clinical phenotype of TCP has undergone marked changes since its ...Tropical calcific pancreatitis(TCP)is a form of chronic non-alcoholic pancreatitis initially reported in the developing parts of the tropical world.The clinical phenotype of TCP has undergone marked changes since its first description in 1968.The disease is now seen in relatively older people with less severe symptoms.In addition,there are varying reports on the proportion of cases presenting with imaging abnormalities like calcification,ductal dilation,and glandular atrophy.Significant progress has also been made in understanding the etiopathology of TCP.The role of malnutrition and cassava toxicity in its pathogenesis is disproven and few studies have focused on the role of micronutrient deficiency and oxidative stress in the etiopathogenesis of TCP.Emerging evidence support an important role for genetic risk factors in TCP.Several studies have shown that,rather than mutations in trypsinogens,variants in serine protease inhibitor kazal type 1,cathepsin B,chymotrypsin C,cystic fibrosis transmembrane regulator,and carboxypeptidase A1,predict risk of TCP.These studies also provided evidence of mutational heterogeneity between TCP and chronic pancreatitis in Western populations.The current review summarizes recent advances that have implications in the understanding of the pathophysiology and thus,heterogeneity in genotype-phenotype correlations in TCP.展开更多
PKHD1 mutations are generally considered to cause autosomal recessive polycystic kidney disease(ARPKD).ARPKD is a rare disorder and one o f the most severe conditions leading to end-stage renal disease in childhood.Wi...PKHD1 mutations are generally considered to cause autosomal recessive polycystic kidney disease(ARPKD).ARPKD is a rare disorder and one o f the most severe conditions leading to end-stage renal disease in childhood.With the biallelic deletion mutation,patients have difficulty in surviving the perinatal period,resulting in perinatal or neonatal death.This study retrospectively analyzed patient characteristics,imaging characteristics,laboratory examinations and family surveys from 7 Chinese children with different PKHD1 gene mutations diagnosed by high-throughput sequencing from January 2014 to February 2018.O f the 7 children,there were 3 males and 4 females.Eight missense mutations,two frameshift mutations,two deletion mutations,and two intronic slicing mutations were identified.Six of the mutations have not previously been identified.In the literature search,we identified a total of 29 Chinese children with PKHD1 mutations.The missense mutation c.2507T>C in exon 24 was found in one patient in our study,and five patients with liver fibrosis but normal renal function were reported in the literature.The missense mutation c.5935G>A in exon 37 was found in two patients in our study and three cases in the literature.Four patients had renal failure at an age as young as 1 year of those five patients with the missense mutation c.5935G>A in exon 37.It was concluded that:(1)Kidney length more than 2-3 SDs above the mean and early-onset hypertension might be associated with PKHDI-associated ARPICD;(2)The more enlarged the kidney size is,the lower the renal function is likely to be;(3)c.5935G>A may be a hot spot that leads to early renal failure in Chinese children with PKHD1 mutations;(4)c.2507T>C may be a hot-spot mutation associated with hepatic lesions in Chinese children with PKHD1.展开更多
BACKGROUND Spinocerebellar ataxia type 3(SCA3)is a rare neurodegenerative disease with high genetic heterogeneity.SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles,...BACKGROUND Spinocerebellar ataxia type 3(SCA3)is a rare neurodegenerative disease with high genetic heterogeneity.SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles,dysphagia,lingual fibrillation,pyramidal tract sign,and extrapyramidal system sign.However,it rarely has clinical manifestations similar to Parkinson-like symptoms,and is even rarer in patients sensitive to dopamine.We report a patient initially diagnosed with dopamine-responsive dystonia who was ultimately diagnosed with SCA3 by genetic testing,which was completely different from the initial diagnosis.CASE SUMMARY A 40-year-old Chinese woman was admitted to hospital due to severe inflexibility.At the beginning of the disease,she presented with anxiety and sleep disorder.At the later stage,she presented with gait disorder,which was similar to Parkinson's disease.Her medical history was unremarkable,but her mother,grandmother,and uncle all had similar illnesses and died due to inability to take care of themselves and related complications.Laboratory and imaging examinations showed no abnormalities,but electromyography and electroencephalography revealed delayed somatosensory evoked potentials and slow background rhythm,respectively.Her symptoms fluctuated during the daytime,and we initially diagnosed her with dopamine-responsive dystonia.After treatment with lowdose levodopa,the patient’s symptoms were significantly improved,but the final genetic diagnosis was SCA3.CONCLUSION SCA3 has various clinical phenotypes and needs to be differentiated from Parkinson's syndrome and dopamine-responsive dystonia.展开更多
<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. &l...<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. <strong>Methods:</strong> 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. <strong>Results:</strong> There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). <strong>Conclusion:</strong> The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.展开更多
The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epid...The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epidemiological and molecular approaches, the authors studied： （a） the frequency of the HH main mutations; （b） the association between mutations and HH cases. The majority of patients with HH are homozygous for the C282Y mutation of the HFE gene. A second mutation （H63D） is more widely distributed and its connection with HH isn＇t clear, but a low penetrance is attributed to this variant. The population-based study consists of three steps： （1） determination of iron biochemical parameters, （2） genetic test, and （3） sequencing of HFE gene and bioinformatics studies. A case report is presented in a 41-year-old male （genotype： H63D/wt） with biochemical and clinical evidences of HH, in absence of secondary iron overload factors. In the cohort of studied patients （150M：62F）, there are 18 homozygous patients; H63D/H63D genotype is found in 11 cases. In the heterozygous group, H63D/wt is the predominant genotype （61/68 subjects）. All the H63D/wt residents in the same village （Mont.） show altered biochemical parameter levels. In our case study, a substitution localized into the HFE promoter （nt225A 〉 C） is found. Results show that the H63D genotype is responsible for most cases of HH. The peculiar clinical manifestation found in Mont. suggests a founder effect. In our case, the iron overload is related to a presence of an undetected mutation, critical for the transcriptional regulation of the HFE gene.展开更多
A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian ...A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses(compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.展开更多
Objective To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy(HCM)families.Methods A retrospective cohort study was conducted on 5...Objective To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy(HCM)families.Methods A retrospective cohort study was conducted on 527 unrelated HCM probands who were first diagnosed at the First Affliated Hospital of Air Force Medical University(Xijing Hospital)from February 2014 to July 2018,and the high-throughput whole exome targeted sequencing of 96 genes related to hereditary cardiovascular disease was performed on the probands.The probands carrying the MYH7-R453C mutation were screened out,and their family members carrying the mutation were verified using Sanger sequencing.Healthy individuals without family history of genetic diseases from the same period and ethnicity were recruited as controls.Clinical data such as echocardiography,12-lead electrocardiogram,andd cardiacmagneticrresonance imaging of the probands and their family members were collected,and the correlation between patient genotype and clinical phenotype was analyzed.Endpoint or key events were recorded through hospital re-examination or telephoneffollow-up.Results The MYH7-R453C mutation was detected in 5 HCM probands,and clinical data and genetic results of 20 family members,including probands,were collected.Among them,13 carried the MYH7-R453C mutation,of which 12 were diagnosed with HCM,and one child(F1Ⅲ_(5))experienced early changes of HCM.The seven family members who did not carry the MYH7-R453C mutation had normal echocardiograms and 12-lead electrocardiograms.Among the 12 patients diagnosed with HCM,2 experienced(F2Ⅱ_(7),F5Ⅰ_(2))sudden cardiac death,2 experienced(F1Ⅲ_(1),F3Ⅲ_(3))events of sudden cardiac death survival,2(F1Ⅱ_(2),F3,Ⅱ_(1))died from heart failure during the follow-up period.Combined with the initial visit and follow-up,4 families(F1,F2,F3,F5)had a family history of sudden death,among which 3families probands or multiple family members experiencing sudden death before the age of 30 and adverse outcomes such as implantation of implantable cardioverter-defibrillators after sudden death survival.Conclusion In the five families with HCM carrying MYH7-R453C mutations,genotype is highly correlated with clinical phenotype,and patients have a high risk of sudden death and poor prognosis.Early diagnosis of individuals carrying the MYH7-R453C gene mutation,both within the patient's family and in the patients themselves,is crucial for initiating early treatment,preventing sudden death and assessing prognosis.展开更多
Objective To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17(DEE17)caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of...Objective To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17(DEE17)caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of their genetic variants.Methods A retrospective analysis was conducted on the clinical data of 5 children diagnosed with GNAO1-related DEE17 in the Department of Neurology,Children's Hospital of Soochow University from January 2019 to October 2024.展开更多
Background:The increasing incidence of inflammatory bowel disease(IBD)presents significant medical and societal challenges.A well-designed IBD database is crucial for both epidemiological studies and clinical manageme...Background:The increasing incidence of inflammatory bowel disease(IBD)presents significant medical and societal challenges.A well-designed IBD database is crucial for both epidemiological studies and clinical management.However,inconsistencies between regional databases hinder cross-institutional and international research,especially between Eastern and Western societies.Methods:We developed a new IBD database,the 301 IBD database,integrating the IBD clinical characteristics from the Penn IBD database(USA)and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital(PLAGH).We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023.Results:The 301 IBD database contains 490 items in 6 sections including demographic characteristics,personal history,clinical phenotype,disease activity,laboratory tests and examinations,and treatment.Features of the 301 IBD database include inpatient focus,biochemical indicators and opportunistic infection focus,and more about ulcerative colitis(UC)-associated complications.Single-center analysis revealed an increasing hospitalization trend,from 2.35%in 2008 to 3.94%in 2023.We found that the clinical characteristics of our UC inpatients are predominantly male(62.5%),extensive lesions(55.1%),low usage of biologics(4.1%),and a high incidence of UC-CRC(3.0%).The clinical characteristics of CD inpatients included male predominance(68.39%),early onset age(35.43±14.75-year-old),and high rate of surgery(25.81%).Conclusion:The 301 IBD database,integrating Eastern and Western clinical data,provides a valuable tool for IBD clinical research.Future international,multicenter collaborations are expected to further enhance its utility.展开更多
Traditional Chinese medicine （TCM） investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtai...Traditional Chinese medicine （TCM） investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network （CPN）, in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.展开更多
Objective To study the relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex(TSC).Methods The clinical data of76 patients with TSC diagnosed in Guangdong 999 Brain Hospi...Objective To study the relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex(TSC).Methods The clinical data of76 patients with TSC diagnosed in Guangdong 999 Brain Hospital were collected between May 2007 and 2014 and then TSC gene mutation analysis was performed.Genotype-phenotype analyses for all the patients were also carried out.Results Fifty of the 76(66%)patients展开更多
The autism susceptibility candidate 2(AUTS2)gene1,2 at 7q11.2 was first identified and found disrupted because of a balanced translocation in a pair of monozygotic twins with autism spectrum disorder(ASD).Analysis of ...The autism susceptibility candidate 2(AUTS2)gene1,2 at 7q11.2 was first identified and found disrupted because of a balanced translocation in a pair of monozygotic twins with autism spectrum disorder(ASD).Analysis of 60 novel cases suggests that clinical phenotypes are more closely associated with intellectual disability rather than directly linked to ASD features.Human AUTS2 is a highly conserved gene that spans 1.2 Mb.Human AUTS2 protein has two major isoforms,full-length(1259 aa)and C-terminal(711 aa).Phenotypic analysis of patients indicated that they had borderline to severe intellectual disability/developmental delay,and 83%e100%had microcephaly.Mild dysmorphology was present.Specific traits of autism(like obsessive behavior)were seen frequently(83%).AUTS2 is also associated with alcohol consumption,heroin dependence,schizophrenia,and dyslexia,as analyzed using GWAS studies.展开更多
基金This cohort study is funded by the China National Natural Science Foundation(No.81970618)China National Clinical Research Centre Foundation(No.NCRC-2019-GP-02)+2 种基金Chongqing Science and Technology Commission project(No.cstc2016jcyjA0440)Chongqing Science and Technology plan project of Yuzhong District(No.2017045),Science and Technology Research Project of Chongqing Education Commission(No.KJZD-M201900401)the central government directs special funds for local science and technology development.
文摘Understanding the association between the genetic and clinical phenotypes in children with nephrotic syndrome(NS)of different etiologies is critical for early clinical guidance.We employed whole-exome sequencing(WES)to detect monogenic causes of NS in a multicenter cohort of 637 patients.In this study,a genetic cause was identified in 30.0%of the idiopathic steroid-resistant nephrotic syndrome(SRNS)patients.Other than congenital nephrotic syndrome(CNS),there were no significant differences in the incidence of monogenic diseases based on the age at manifestation.Causative mutations were detected in 39.5%of patients with focal segmental glomerulosclerosis(FSGS)and 9.2%of those with minimal change disease(MCD).In terms of the patterns in patients with different types of steroid resistance,a single gene mutation was identified in 34.8%of patients with primary resistance,2.9%with secondary resistance,and 71.4%of children with multidrug resistance.Among the various intensified immunosuppressive therapies,tacrolimus(TAC)showed the highest response rate,with 49.7%of idiopathic SRNS patients achieving complete remission.Idiopathic SRNS patients with monogenic disease showed a similar multidrug resistance pattern,and only 31.4%of patients with monogenic disease achieved a partial remission on TAC.During an average 4.1-year follow-up,21.4%of idiopathic SRNS patients with monogenic disease progressed to end-stage renal disease(ESRD).Collectively,this study provides evidence that genetic testing is necessary for presumed steroid-resistant and idiopathic SRNS patients,especially those with primary and/or multidrug resistance.
基金supported by the National Natural Science Foundation of China(31770935,81873531,31970616)the Distinguished Professorship Program of Jiangsu Province to YF+2 种基金the Distinguished Professorship Program of Jiangsu Province to RMthe National Undergraduate Training Programs for Innovation(201710304030Z)the National Undergraduate Training Programs for Innovation(201810304026Z).
文摘Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA”is its accessibility.In cancer cells,aberrant chromatin accessibility is recognized as one of the major hallmarks.Understanding such events requires high-throughput screening,such as Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq),which generates large-scale data that are puzzling for biologists.However,existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes.Here,we developed Shiny Pan-cancer Accessible Chromatin Explorer(SPACE)as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types.
基金supported by Special Fund for Clinical Medicine of Chinese Medical Association (12040690369)
文摘The mutations of CARD15 gene and clinical features of Chinese patients with Blau syndrome were analyzed. We identified10 missense mutations, out of which five were new: R334 L, E383 D, R471 C, C495 R and D512 F. The rest of them, R334 W,R334Q, G481 D, M513 T and R587 C, have been reported previously. Among all the mutations, R334 W, R334 Q and C495 R had the highest frequency. Blau syndrome was found at early age after birth. It began with lepidic rash and symmetric polyarthritis and was phenotypically characterized by typical rash, arthritis, iridocyclitis and arteritis. Cardiac involvement was also found in Blau syndrome. In addition to nerve deafness, renal involvement, osteochondroma and central nervous system involvement were also found in our patients. Therefore, Chinese children with Blau syndrome have unique gene mutations and complicated clinical phenotypes. Pathologic examination and CARD15 mutation testing should be considered for diagnosis as early as possible for suspected patients.
基金supported by grants from National Natural Science Foundation of China (82402543)National High Level Hospital Clinical Research Funding (2022-PUMCH-B-109)+2 种基金CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-020)Opening Foundation of Agile and Intelligent Computing Key Laboratory of Sichuan ProvinceSpecial Research Fund for Central Universities,Peking Union Medical College (3332024120)
文摘BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.
文摘The distribution of hepatitis B virus genotype in Hubei province and its clinical signifi- cance were investigated. HBV genotypes of 276 patients were detected by PCR-microplate sandwich hybrization-ELISA technique. The level of HBV DNA was detected by using PCR-fluorescence quantification test. Among 276 patients, there were 78 cases of HBV asymptomatic carriers, 110 cases of chronic hepatitis B (CHB), 62 cases of severe hepatitis (SH) or liver cirrhosis (LC) and 26 cases of hepatocellular carcinoma (HCC). The genotypes of HBV included C, B, mixtures (B+C, B+D, C+D) and D, accounting for 55.8%, 25.4%, 16.7% and 2.1% respectively. The average level of HBV DNA in genotypes C, B, mixtures and D was 1.20×106, 7.81×104, 3.26×105 and 5.01×104 cop- ies/mL respectively. The ratio of SH, LC and HCC in genotype B, C and mixtures was 20%, 30% and 48% respectively. Statistical analysis revealed the percentage of genotype mixtures infection was sig- nificantly higher than that of genotype B infection. There was no significant difference in the per- centage between genotype B and genotype C or between genotype C and mixtures. The distribution of genotype B, C and mixtures in SH, LC and HCC was significantly different. The frequency of HCC was zero in patients with co-infection. Genotype D was only related with SH and LC. The in- creased ALT could be converted to categorical grades of severity. From mild, moderate to severity, the prevalence of genotype C showed an opposite trend, although no statistically significant differ- ence was observed. The HBeAg positive rate was higher in patients with genotype C infection than in those with genotype B, especially in the patients whose ages were from 31 to 40 years old. Compared with genotype B, genotype C showed a higher HBeAg positive rate in patients with SH and LC. The percentage of SH, LC and HCC was higher in patients with genotype C and mixtures infection. On the contrary, the percentage of genotype B was lower. The HBeAg positive rate in patients with genotype C infection was higher than those with genotype B infection. Genotype C and mixtures may be associated with development of severe liver disease.
文摘Objective To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene,and to improve clinicians'understanding of the ALG14 gene and its associated disorders.
文摘Covering the entire human body, the skin is considered to be one of the most important organs, since it is the first line of protection against chemical and biological external agents. Although the skin protects tissues and organs against external aggression, it can still be unbalanced by various skin diseases, such as psoriasis. This non-contagious inflammatory dermatosis is characterized by the occurrence of erythematous lesions of various sizes covered with whitish scales. This scaling of the skin is the result of a rapid renewal of the epidermis, occurring over five to seven days instead of 28 days. Psoriasis vulgaris, or plaque psoriasis, is the most common form of this disease and is therefore commonly referred to by the term “psoriasis”. This work is a review of the literature on plaque psoriasis, aiming at a better comprehension of the pathology at the histological level, but also to understand the genetic and environmental factors associated with this inflammatory dermatosis.
文摘Objective The occurrence characteristic of Kashin Beck Disease (KBD) in pedigrees ascertained on the basis of one proband was estimated. Methods A total of 255 individuals in 40 pedigrees were collected from areas in the Shaanxi Province. Results ① Parents and siblings of index cases have a 3-4 times higher risk than a random unrelated individual. The odds ratio for disease is higher in mothers than in fathers of index cases; ② Prevalence in relatives of index cases (K r= 59.2% ) greatly exceeds population prevalence (K= 17.5% ); ③ K r increases with sibship size; ④ There is no significant difference of K r for male and female siblings of index cases. Also, population prevalence is not sex specific. Conclusion In conjunction with environmental agents, genetics may play an important role in KBD etiology.
基金support from the Council of Scientific and Industrial Research,Indian Council of Medical ResearchDepartment of Biotechnology,Government of India,India
文摘Tropical calcific pancreatitis(TCP)is a form of chronic non-alcoholic pancreatitis initially reported in the developing parts of the tropical world.The clinical phenotype of TCP has undergone marked changes since its first description in 1968.The disease is now seen in relatively older people with less severe symptoms.In addition,there are varying reports on the proportion of cases presenting with imaging abnormalities like calcification,ductal dilation,and glandular atrophy.Significant progress has also been made in understanding the etiopathology of TCP.The role of malnutrition and cassava toxicity in its pathogenesis is disproven and few studies have focused on the role of micronutrient deficiency and oxidative stress in the etiopathogenesis of TCP.Emerging evidence support an important role for genetic risk factors in TCP.Several studies have shown that,rather than mutations in trypsinogens,variants in serine protease inhibitor kazal type 1,cathepsin B,chymotrypsin C,cystic fibrosis transmembrane regulator,and carboxypeptidase A1,predict risk of TCP.These studies also provided evidence of mutational heterogeneity between TCP and chronic pancreatitis in Western populations.The current review summarizes recent advances that have implications in the understanding of the pathophysiology and thus,heterogeneity in genotype-phenotype correlations in TCP.
基金This project was supported by the National Natural Science Foundation of China(No.81873596).
文摘PKHD1 mutations are generally considered to cause autosomal recessive polycystic kidney disease(ARPKD).ARPKD is a rare disorder and one o f the most severe conditions leading to end-stage renal disease in childhood.With the biallelic deletion mutation,patients have difficulty in surviving the perinatal period,resulting in perinatal or neonatal death.This study retrospectively analyzed patient characteristics,imaging characteristics,laboratory examinations and family surveys from 7 Chinese children with different PKHD1 gene mutations diagnosed by high-throughput sequencing from January 2014 to February 2018.O f the 7 children,there were 3 males and 4 females.Eight missense mutations,two frameshift mutations,two deletion mutations,and two intronic slicing mutations were identified.Six of the mutations have not previously been identified.In the literature search,we identified a total of 29 Chinese children with PKHD1 mutations.The missense mutation c.2507T>C in exon 24 was found in one patient in our study,and five patients with liver fibrosis but normal renal function were reported in the literature.The missense mutation c.5935G>A in exon 37 was found in two patients in our study and three cases in the literature.Four patients had renal failure at an age as young as 1 year of those five patients with the missense mutation c.5935G>A in exon 37.It was concluded that:(1)Kidney length more than 2-3 SDs above the mean and early-onset hypertension might be associated with PKHDI-associated ARPICD;(2)The more enlarged the kidney size is,the lower the renal function is likely to be;(3)c.5935G>A may be a hot spot that leads to early renal failure in Chinese children with PKHD1 mutations;(4)c.2507T>C may be a hot-spot mutation associated with hepatic lesions in Chinese children with PKHD1.
基金the National Natural Science Foundation of China,No.81874448 and No.81973789.
文摘BACKGROUND Spinocerebellar ataxia type 3(SCA3)is a rare neurodegenerative disease with high genetic heterogeneity.SCA3 mainly manifests as progressive cerebellar ataxia accompanied by paralysis of extraocular muscles,dysphagia,lingual fibrillation,pyramidal tract sign,and extrapyramidal system sign.However,it rarely has clinical manifestations similar to Parkinson-like symptoms,and is even rarer in patients sensitive to dopamine.We report a patient initially diagnosed with dopamine-responsive dystonia who was ultimately diagnosed with SCA3 by genetic testing,which was completely different from the initial diagnosis.CASE SUMMARY A 40-year-old Chinese woman was admitted to hospital due to severe inflexibility.At the beginning of the disease,she presented with anxiety and sleep disorder.At the later stage,she presented with gait disorder,which was similar to Parkinson's disease.Her medical history was unremarkable,but her mother,grandmother,and uncle all had similar illnesses and died due to inability to take care of themselves and related complications.Laboratory and imaging examinations showed no abnormalities,but electromyography and electroencephalography revealed delayed somatosensory evoked potentials and slow background rhythm,respectively.Her symptoms fluctuated during the daytime,and we initially diagnosed her with dopamine-responsive dystonia.After treatment with lowdose levodopa,the patient’s symptoms were significantly improved,but the final genetic diagnosis was SCA3.CONCLUSION SCA3 has various clinical phenotypes and needs to be differentiated from Parkinson's syndrome and dopamine-responsive dystonia.
文摘<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. <strong>Methods:</strong> 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. <strong>Results:</strong> There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). <strong>Conclusion:</strong> The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.
文摘The present study aims to investigate the genotype-phenotype correlation of the hereditary hemochromatosis （HH）, a genetic disorder of iron metabolism, in Matera province （Basilicata, Italy）. Integrating both epidemiological and molecular approaches, the authors studied： （a） the frequency of the HH main mutations; （b） the association between mutations and HH cases. The majority of patients with HH are homozygous for the C282Y mutation of the HFE gene. A second mutation （H63D） is more widely distributed and its connection with HH isn＇t clear, but a low penetrance is attributed to this variant. The population-based study consists of three steps： （1） determination of iron biochemical parameters, （2） genetic test, and （3） sequencing of HFE gene and bioinformatics studies. A case report is presented in a 41-year-old male （genotype： H63D/wt） with biochemical and clinical evidences of HH, in absence of secondary iron overload factors. In the cohort of studied patients （150M：62F）, there are 18 homozygous patients; H63D/H63D genotype is found in 11 cases. In the heterozygous group, H63D/wt is the predominant genotype （61/68 subjects）. All the H63D/wt residents in the same village （Mont.） show altered biochemical parameter levels. In our case study, a substitution localized into the HFE promoter （nt225A 〉 C） is found. Results show that the H63D genotype is responsible for most cases of HH. The peculiar clinical manifestation found in Mont. suggests a founder effect. In our case, the iron overload is related to a presence of an undetected mutation, critical for the transcriptional regulation of the HFE gene.
基金supported in part by General Research Fund, Research Grants Council of Hong Kong (HKU 780113M)Area of Excellence program (AoE/M-12/06)+1 种基金University Grants Committee of Hong Kong SARResearch Fund for the Control of Infectious Diseases, Hong Kong SAR government (11100742)
文摘A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses(compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.
文摘Objective To analyze the relationship between genotype and clinical phenotype of the MYH7-R453C mutation in five Chinese hypertrophic cardiomyopathy(HCM)families.Methods A retrospective cohort study was conducted on 527 unrelated HCM probands who were first diagnosed at the First Affliated Hospital of Air Force Medical University(Xijing Hospital)from February 2014 to July 2018,and the high-throughput whole exome targeted sequencing of 96 genes related to hereditary cardiovascular disease was performed on the probands.The probands carrying the MYH7-R453C mutation were screened out,and their family members carrying the mutation were verified using Sanger sequencing.Healthy individuals without family history of genetic diseases from the same period and ethnicity were recruited as controls.Clinical data such as echocardiography,12-lead electrocardiogram,andd cardiacmagneticrresonance imaging of the probands and their family members were collected,and the correlation between patient genotype and clinical phenotype was analyzed.Endpoint or key events were recorded through hospital re-examination or telephoneffollow-up.Results The MYH7-R453C mutation was detected in 5 HCM probands,and clinical data and genetic results of 20 family members,including probands,were collected.Among them,13 carried the MYH7-R453C mutation,of which 12 were diagnosed with HCM,and one child(F1Ⅲ_(5))experienced early changes of HCM.The seven family members who did not carry the MYH7-R453C mutation had normal echocardiograms and 12-lead electrocardiograms.Among the 12 patients diagnosed with HCM,2 experienced(F2Ⅱ_(7),F5Ⅰ_(2))sudden cardiac death,2 experienced(F1Ⅲ_(1),F3Ⅲ_(3))events of sudden cardiac death survival,2(F1Ⅱ_(2),F3,Ⅱ_(1))died from heart failure during the follow-up period.Combined with the initial visit and follow-up,4 families(F1,F2,F3,F5)had a family history of sudden death,among which 3families probands or multiple family members experiencing sudden death before the age of 30 and adverse outcomes such as implantation of implantable cardioverter-defibrillators after sudden death survival.Conclusion In the five families with HCM carrying MYH7-R453C mutations,genotype is highly correlated with clinical phenotype,and patients have a high risk of sudden death and poor prognosis.Early diagnosis of individuals carrying the MYH7-R453C gene mutation,both within the patient's family and in the patients themselves,is crucial for initiating early treatment,preventing sudden death and assessing prognosis.
文摘Objective To summarize the clinical characteristics of 5 children with developmental epileptic encephalopathy type 17(DEE17)caused by GNAO1 gene variants confirmed by whole-exome sequencing and analyze the features of their genetic variants.Methods A retrospective analysis was conducted on the clinical data of 5 children diagnosed with GNAO1-related DEE17 in the Department of Neurology,Children's Hospital of Soochow University from January 2019 to October 2024.
文摘Background:The increasing incidence of inflammatory bowel disease(IBD)presents significant medical and societal challenges.A well-designed IBD database is crucial for both epidemiological studies and clinical management.However,inconsistencies between regional databases hinder cross-institutional and international research,especially between Eastern and Western societies.Methods:We developed a new IBD database,the 301 IBD database,integrating the IBD clinical characteristics from the Penn IBD database(USA)and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital(PLAGH).We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023.Results:The 301 IBD database contains 490 items in 6 sections including demographic characteristics,personal history,clinical phenotype,disease activity,laboratory tests and examinations,and treatment.Features of the 301 IBD database include inpatient focus,biochemical indicators and opportunistic infection focus,and more about ulcerative colitis(UC)-associated complications.Single-center analysis revealed an increasing hospitalization trend,from 2.35%in 2008 to 3.94%in 2023.We found that the clinical characteristics of our UC inpatients are predominantly male(62.5%),extensive lesions(55.1%),low usage of biologics(4.1%),and a high incidence of UC-CRC(3.0%).The clinical characteristics of CD inpatients included male predominance(68.39%),early onset age(35.43±14.75-year-old),and high rate of surgery(25.81%).Conclusion:The 301 IBD database,integrating Eastern and Western clinical data,provides a valuable tool for IBD clinical research.Future international,multicenter collaborations are expected to further enhance its utility.
文摘Traditional Chinese medicine （TCM） investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network （CPN）, in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.
文摘Objective To study the relationship between gene mutation and clinical phenotype in patients with tuberous sclerosis complex(TSC).Methods The clinical data of76 patients with TSC diagnosed in Guangdong 999 Brain Hospital were collected between May 2007 and 2014 and then TSC gene mutation analysis was performed.Genotype-phenotype analyses for all the patients were also carried out.Results Fifty of the 76(66%)patients
基金founded by SFR Cap Santé,Universitéde Reims Champagne-Ardenne,Reims,France to Aude-Marie Lepagnol-Bestel,a European Grant ERA-Net Cofund Action on Nanomedicine under Horizon 2020 Euronanomed 3(project MoDiaNo)CNES(Centre National d'Etudes Spatiales)grant(MemoBion)to Michel Simonneau.
文摘The autism susceptibility candidate 2(AUTS2)gene1,2 at 7q11.2 was first identified and found disrupted because of a balanced translocation in a pair of monozygotic twins with autism spectrum disorder(ASD).Analysis of 60 novel cases suggests that clinical phenotypes are more closely associated with intellectual disability rather than directly linked to ASD features.Human AUTS2 is a highly conserved gene that spans 1.2 Mb.Human AUTS2 protein has two major isoforms,full-length(1259 aa)and C-terminal(711 aa).Phenotypic analysis of patients indicated that they had borderline to severe intellectual disability/developmental delay,and 83%e100%had microcephaly.Mild dysmorphology was present.Specific traits of autism(like obsessive behavior)were seen frequently(83%).AUTS2 is also associated with alcohol consumption,heroin dependence,schizophrenia,and dyslexia,as analyzed using GWAS studies.
