Age of onset of diabetes and all-cause mortality

Diabetes mellitus continues to present a large social,financial and health system burden across the world.The relationship between age of onset of the different types of diabetes and all-cause mortality is uncertain.In this review paper,the relationship between age of onset of the different types of diabetes and all-cause mortality will be reviewed and an update of the current evidence will be presented.There is strong evidence of the relationship between age of onset of type 2 diabetes mellitus(T2 DM) and all-cause mortality,good evidence of the relationship between age of onset of T1 DM and all-cause mortality and no evidence of the relationship between age of onset of gestational diabetes or prediabetes and all-cause mortality.Further research is needed to look at whether aggressive management of earlier onset of T2 DM can help to reduce premature mortality.

Early Age of Onset, Multiple Primary Malignancies and Poor Prognosis Are Indicative of an Inherited Predisposition to Esophageal Squamous Cell Carcinoma in Familial Rather Than Sporadic Disease- An Update Based on 14- to 23-year Follow-up

OBJECTIVE To demonstrate the effects of an inherited predisposition to familial esophageal squamous cell carcinoma （ESCC） through the comparison and analysis of the clinicopathologic differences between familial and sporadic ESCC cases. METHODS Differences in age of onset, prevalence rates of double primary ESCC, and survival rates between familial ESCC （n = 476） and sporadic ESCC cases （n = 1226） were analyzed. RESULTS Overall, familial ESCC cases showed a significantly younger age of onset （51.9±8.2 vs. 53.4 ±8.0, Pt.test = 0.00）, a significantly higher prevalence rate for double ESCC （2.73 % vs. 1.22%, adjusted with TNM：χMH2 = 4.029, P = 0.045）, and a lower survival rate than in sporadic cases （Pwald = 0.04）. The familial cases showed both a younger age of onset and poorer survival in most subgroups, and the differences were more marked in early-stage rather than in the .late-stage disease groups. CONCLUSION Theses findings confirm the existence of familial as opposed to sporadic ESCC. By the theory of the ＂two-hit＂ origin of cancer, these findings also suggest that the ＂first hit＂, a genetic predisposition, can affect the age of onset, number of primary carcinomas, and the prognosis for familial ESCC patients.

Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia

AIM:To investigate the role of protein tyrosin phosphatase 22(PTPN22),maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes(T1D)in Continental Italy and Sardinian populations.METHODS:Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia.PTPN22 genotype was determined by DNA analysis.Maternal age at conception and age at onset of disease were obtained from clinical records.χ2 test of independence,student t test for differences between means and odds ratio analysis were carried out by SPSS programs.Three way contingency table analysis was carried out according to Sokal and Rohlf.RESULTS:The pattern of association between PTPN22and T1D is similar in Continental Italy and Sardinia:the proportion of*T allele carriers is 13.6%in T1D vs6.7%in controls in Continental Italy while in Sardinia is 7.3%in T1D vs 4.4%in controls.The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy:the proportion of newborn from mother aging more than 32 years is89.3%in T1D vs 32.7%in consecutive newborn in Sardinia(P<10-6)while in Continental Italy is 32.2%in T1D vs 19.1%in consecutive newborns(P=0.005).This points to an important role of ethnicity.A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia.PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia.Maternal age does not influence significantly age at onset in Italy(8.2 years in T1D infants from mothers aging32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years:P=0.824)while in Sardinia a border line effect is observed(5.75 years in T1D infants from mothers aging 32 years or less vs7.54 years in T1D infants from mothers aging more than 32 years:P=0.062).No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males(8.07 years in males vs 6.3 years in females:P=0.002).CONCLUSION:The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.

Correlation between age of onset and gastrointestinal stenosis in hospitalized patients with Crohn's disease

BACKGROUND Patients affected by Crohn's disease(CD)are more likely to develop gastrointestinal stenosis and often undergo surgery during the duration of disease.AIM To identify the risk factors for gastrointestinal stenosis in hospitalized CD patients in China.METHODS The clinical data of CD patients hospitalized at the Seventh Medical Center,Chinese People's Liberation Army General Hospital from January 2010 to December 2018 were included.Patients with gastrointestinal stenosis were compared to those without gastrointestinal stenosis for clinical variables.The risk factors for gastrointestinal stenosis were identified using univariate and multivariable logistic regression analyses.The treatments for patients with gastrointestinal stenosis were analyzed,and the characteristics of different treatment methods were discussed.RESULTS The incidence of gastrointestinal stenosis was 59.02%in the 122 hospitalized CD patients.Age of onset of more than 40 years(odds ratio[OR]=3.072,95%confidence interval[CI]:1.298-7.272,P=0.009)and duration of disease of more than 5 years(OR=2.101,95%CI:1.002-4.406,P=0.048)were associated with the occurrence of gastrointestinal stenosis.Fifteen(20.83%)patients did not undergo surgery and received internal medicine and nutrition treatment.Surgical treatments were performed in 72.22%(52)of cases.The rate of postoperative complications was 15.38%(8 cases),and during a median follow-up period of 46 mo,11.54%(6 cases)underwent reoperation.A total of 29.17%(21 cases)were treated with endoscopic therapy,and during a median follow-up period of 32 mo,76.19%(16 cases)had no surgical event,23.81%(5 cases)failed to avoid surgical treatments,and no serious postoperative complications occurred after endoscopic therapy.CONCLUSION Age of onset of more than 40 years and duration of disease of more than 5 years may be strongly correlated with a higher risk of gastrointestinal stenosis in hospitalized CD patients.Endoscopic therapy for gastrointestinal stenosis is relatively safe and effective,and may help to prevent or delay surgery.

Earlier onset and multiple primaries in familial as opposed to sporadic esophageal cancer

AIM: To study the differences in onset age and multiple primary cancers between familial and sporadic esophageal squamous cell carcinoma(ESCC).METHODS: The differences in onset age and multiple primary cancers were analyzed between ESCC patients with(n = 766) and without(n = 1776) a family history of the cancer. The cases analyzed constituted all consecutive patients who had undergone cure-intent surgery at the Department of Thoracic Surgery of the 4th Hospital of Hebei Medical University from January 1 1975 to December 31 1989. Because we also originally aimed to examine the difference in survival time, only older subjects with a long follow-up period were selected.RESULTS: Overall, patients with ESCC and a positive family history of the cancer had a significantly younger age at onset and more multiple primary cancers than those without a positive family history(51.83 ± 8.39 vs 53.49 ± 8.23 years old, P = 0.000; 5.50% vs 1.70%, P = 0.000). Both of these differences were evident in subgroup analyses, however, no correlations were observed. While age at onset differed significantly by family history in males, smokers, and drinkers, the difference in multiple primary cancers by family history was significant in nonsmoking, nondrinking, and younger onset patients. In multivariate analysis, age over 50 years, tobacco smoking, and multiple primary cancers were found to be significant predictors of familial cancer: the corresponding OR(95%CI) and P-value were 0.974(0.963-0.985) and 0.000; 1.271(1.053-1.535) and 0.012; and 4.265(2.535-7.176) and 0.000, respectively.CONCLUSION: Patients with ESCC and a positive family history of the cancer had a significantly younger onset age and more multiple primary cancers than those without a positive family history. Sub-group analyses indicated that younger onset age may be due to the interaction of genetic predisposition and environmental hazards, and multiple primary cancers may only be due to genetic predisposition.

Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis

BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.

Younger age of onset and multiple primary lesions associated with esophageal squamous cell carcinoma cases with a positive family history of the cancer suggests genetic predisposition

Background Previous epidemiological studies have consistently found a positive family history of esophageal cancer is associated with a significantly increased risk of the cancer.However,whether the elevated risk could be attributed to common household exposure or inherited susceptibility is uncertain.This study aimed to highlight the effect of genetic predisposition by noting the significant differences in onset age and multiple primary cancers between esophageal squamous cell carcinoma （ESCC） cases with or without a positive family history of the cancer.Methods Age at onset and the percentage of multiple primary cancers were compared between ESCCs with （n=766） or without （n=1 776） a positive family history of the cancer in a consecutive surgery cohort at the Department of Thoracic Surgery of Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University.Results Overall,ESCCs with a positive family history of the cancer featured both a significantly younger age of onset and significantly more multiple primary cancers than those with a negative family history （onset age 51.83 vs.53.49 years old,P 〈0.01; percent of multiple primary cancers 5.50% vs.1.70%,x2=25.42,P 〈0.01）.Both the differences were evident in subgroup analyses,but did not correlate.While age at onset differed significantly by family history among the male,smoking,and drinking groups,the difference of multiple primary cancers was significant among the otherwise nonsmoking,nondrinking,and younger onset age groups.Conclusions Younger age of onset and multiple primary cancers associated with ESCCs with a positive,as opposed to a negative family history of the cancer,suggest a genetic predisposition.The results of subgroup analyses indicate a younger age of ESCC development results from the interaction of environmental and genetic risk factors,but multiple primary cancers may be related only to genetic predisposition.

Smoking in schizophrenic patients:A critique of the selfmedication hypothesis

A common remark among laypeople, and notably also among mental health workers, is that individuals with mental illnesses use drugs as self-medication to allay clinical symptoms and the side effects of drug treatments. Roots of the self-medication concept in psychiatry date back at least to the 1980 s. Observations that rates of smokers in schizophrenic patients are multiple times the rates for regular smoking in the general population, as well as those with other disorders, proved particularly tempting for a self-medication explanation. Additional evidence came from experiments with animal models exposed to nicotine and the identification of neurobiological mechanisms suggesting self-medication with smoking is a plausible idea. More recently, results from studies comparing smoking and non-smoking schizophrenic patients have led to the questioning of the self-medication hypothesis. Closer examination of the literature points to the possibility that smoking is less beneficial on schizophrenic symptomology than generally assumed while clearly increasing the risk of cancer and other smoking-related diseases responsible for early mortality. It is a good time to examine the evidence for the self-medication concept as it relates to smoking. Our approach is to focus on data addressing direct or implied predictions of the hypothesis in schizophrenic smokers.

Colorectal cancer in the young,many questions,few answers

At a time where the incidence of colorectal cancer,a disease predominantly of developed nations,is showing a decline in those 50 years of age and older,data from the West is showing a rising incidence of this cancer in young individuals.Central to this has been the 75% increase in rectal cancer incidence in the last four decades.Furthermore,predictive data based on mathematical modelling indicates a 124 percent rise in the incidence of rectal cancer by the year 2030-a statistic that calls for collective global thought and action.While predominance of colorectal cancer(CRC) is likely to be in that part of the large bowel distal to the splenic flexure,which makes flexible sigmoidoscopic examination an ideal screening tool,the cost and benefit of mass screening in young people remain unknown.In countries where the incidence of young CRC is as high as 35% to 50%,the available data do not seem to indicate that the disease in young people is one of high red meat consuming nations only.Improvement in our understanding of genetic pathways in the aetiology of CRC,chiefly of the MSI,CIN and CIMP pathway,supports the notion that up to 30% of CRC is genetic,and may reflect a familial trait or environmentally induced changes.However,a number of other germline and somatic mutations,some of which remain unidentified,may play a role in the genesis of this cancer and stand in the way of a clear understanding of CRC in the young.Clinically,a proportion of young persons with CRC die early after curative surgery,presumably from aggressive tumour biology,compared with the majority in whom survival after operation will remain unchanged for five years or greater.The challenge in the future will be to determine,by genetic fingerprinting or otherwise,those at risk of developing CRC and the determinants of survival in those who develop CRC.Ultimately,prevention and early detection,just like for those over 50 years with CRC,will determine the outcome of CRC in young persons.At present,aside from those with an established familial tendency,there is no consensus on screening young persons who may be at risk.However,increasing awareness of this cancer in the young and the established benefit of prevention in older persons,must be a message that should be communicated with medical students,primary health care personnel and first contact doctors.The latter constitutes a formidable challenge.

Smoking increases the risk of extraintestinal manifestations in Crohn's disease

AIM:To demonstrate a high prevalence of extraintestinal manifestations(EIMs)in a prospective populationbased cohort of inflammatory bowel disease(IBD)patients at first diagnosis as well as during the early course of the disease.METHODS:EIMs are common in patients with IBD.Data on the frequency of EIMs have mostly been assessed in patients from tertiary centers;however,data about the prevalence of EIMs at first diagnosis as well as factors influencing their incidence during the early course of disease from prospective population-based cohorts are scarce.We present data of patients of our population-based"Oberpfalz cohort"(Bavaria,Germany)from first diagnosis(up to 3 mo after first diagnosis)as well as during the early course of the disease.Possible risk factors were assessed by calculating the relative risk(RR)as well as using logistic regression analysis.RESULTS:In total,data of 257 newly diagnosed patients with IBD were evaluated[161 Crohn’s disease(CD),96 ulcerative colitis(UC)].Median duration of follow-up was 50 mo after first diagnosis.In 63.4%of all patients(n=163),an EIM was diagnosed at any point during the observation period.At first diagnosis,patients with CD had a significantly increased risk of an EIM[n=69(42.9%)]compared with UC patients[n=21(21.9%);P<0.001;RR=1.96;95%CI:1.30-2.98].Active smoking increased the risk of CD patients developing an EIM during the early course of the disease,but notably not of UC patients(P=0.046;RR=1.96;95%CI:1.01-3.79).In addition,using logistic regression analysis,the need for IBD-related surgery and a young age at first diagnosis were identified as risk factors for the development of an EIM in CD patients.No association with EIMs was found for the factors sex,localization of the disease and positive family history of IBD.In contrast,no key factors which increased the risk of development of an EIM could be identified in UC patients.CONCLUSION:We found a high prevalence of EIM in this cohort at first diagnosis and during the early course of the disease.In patients with CD,smoking,need for surgery and younger age at first diagnosis were risk factors for the development of an EIM.

Impact of age and tumor size on the development of the Kasabach-Merritt phenomenon in patients with kaposiform hemangioendothelioma:a retrospective cohort study

Introduction The Kasabach–Merritt phenomenon(KMP)is a severe complication of kaposiform hemangioendothelioma(KHE).The risk factors for KMP need further investigation.Methods The medical records of patients with KHE were reviewed.Univariate and multivariate logistic regression models were used for the risk factors for KMP,and the area under the receiver operator characteristic(ROC)curve was used to assess the predictive power of risk factors.Results A total of 338 patients with KHE were enrolled.The incidence of KMP was 45.9%.Age of onset(P<0.001,odds ratio[OR]0.939;95%confidence interval[CI]0.914–0.966),lesion size(P<0.001,OR 1.944;95%CI 1.646–2.296),mixed type(P=0.030,OR 2.428;95%CI 1.092–5.397),deep type(P=0.010,OR 4.006;95%CI 1.389–11.556),and mediastinal or retroperitoneal lesion location(P=0.019,OR 11.864;95%CI 1.497–94.003)were correlated with KMP occurrence through multivariate logistic regression.ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset(P<0.001,OR 7.206,95%CI 4.073–12.749)and a lesion diameter of 5.35 cm(P<0.001,OR 11.817,95%CI 7.084–19.714).Bounded by a lesion size of 5.35 cm,we found significant differences in tumor morphology,age of onset,treatments,and hematological parameters.Using an onset age of 4.75 months as a cutoff,we found significant differences in tumor morphology,lesion size,hematological parameters,and prognosis.Conclusion For KHE patients with an onset age<4.75 months and/or lesion diameter>5.35 cm,clinicians should be wary of the occurrence of KMP.Active management is recommended to improve the prognosis.

GCH1 variants contribute to the risk and earlier age-at-onset of Parkinson's disease:a two-cohort case-control study

Background:Common and rare variants of guanosine triphosphate cyclohydrolase 1(GCH1)gene may play important roles in Parkinson's disease(PD).However,there is a lack of comprehensive analysis of GCH1 genotypes,especially in non-coding regions.The aim of this study was to explore the genetic characteristics of GCH1,including rare and common variants in coding and non-coding regions,in a large population of PD patients in Chinese mainland,as well as the phenotypic characteristics of GCH1 variant carriers.Methods:In the first cohort of this case-control study,we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls;then in the second cohort,whole-genome sequencing was performed in sporadic late-onset PD samples(1962 patients),as well as 1279 controls.Variants at target GCH1 regions were extracted,and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test.We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset(AAO)in PD patients.Results:For coding variants,we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls(1.2%VS 0.1%,P<0.0001).In the analysis of possible regulatory variants in GCH1 non-coding regions,rs12323905(P=0.001,odds ratio=1.19,95%CI 1.07-1.32)was significantly associated with PD,and variant sets in untranslated regions and intron regions,GCH1 brain-specific expression quantitative trait loci,and two possible promoter/enhancer(GH14J054857 and GH14J054880)were suggestively associated with PD.Genotype phenotype correlation analysis revealed that the carriers of GCH1 deleterious variants manifested younger AAO(P<0.0001),and had milder motor symptoms,milder fatigue symptoms and more autonomic nervous dysfunctions.Meta-analysis of six studies demonstrated 6.4-year earlier onset in GCH1 deleterious variant carriers(P=0.0009).Conclusions:The results highlight the importance of deleterious variants and non-coding variants of GCH1 in PD in Chinese mainland and suggest that GCH1 mutation can influence the PD phenotype,which may help design experimental studies to elucidate the mechanisms of GCH1 in the pathogenesis of PD.

Structure and deformation around the Gyirong basin, north Himalaya, and onset of the south Tibetan detachment system

Gyirong basin and its adjacent area are located at a special position in the Himalayan orogen, where the south Tibetan detachment system (STDS) and N-S trending rift converged. The north Himalayan orogen here can be divided into five petrologic-tectonic units successively from south to north: 1) the Greater Himalayan crystalline complex (GHC); 2) the STDS shear zone; 3) the Tethyan Himalayan sedimentary sequence (THS); 4) the late Cenozoic sedimentary basins, such as Gyirong and Oma basins; and 5) the Malashan gneiss dome. Structural studies show that this area experienced four stages of deformation: 1) the earlier south-directed thrusting, preserved both in the GHC and THS; 2) top-down-to-north slip along the STDS, normal faults related to this slip formed the early controlling structures of the Cenozoic basins,and the tilted pattern of the blocks between the basins indicated a north-directed slip; 3) east-west extension, the resultant N-S trending normal fault formed the eastern boundary of the basins; and 4) late gravitational collapse. Zircon SHRIMP U-Pb dating on the syn-deformational (leuco-) granite along the STDS indicates that the major activity of the STDS occurred at ca. 26 Ma, but its onset may have begun as early as ca. 36 Ma.

s Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function？

Background:Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features,accompanying impaired social function,protracted recovery time,and frequent recurrence.This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia.Methods:In total,547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included.These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders,4th Edition criteria.Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS).Quality of life was assessed by a 36-item Short-form Health Survey (SF-36).Analyses were performed using a continuous or dichotomous (cut-off:30 years)age-of-onset indicator.Results:Early-onset MDD (EOD,＜30 years) was associated with longer illness (P =0.003),unmarried status (P ＜ 0.001),higher neuroticism (P ≤ 0.002) based on the SCL-90-R,and more limited social function and mental health (P =0.006,P =0.007) based on the SF-36 and SDS.The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages.Special clinical features and more impaired social function and quality of life were associated with EOD,as in western studies.Conclusions:EOD often follows higher levels of neuroticism.Age of onset of MDD may be a predictor of clinical features and impaired social function,allowing earlier diagnosis and treatment.

Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China

Background In China, esophageal squamous cell carcinoma （ESCC） and gastric cardia adenocarcinoma （GCA） share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal. Methods The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University. Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males （P 〈0.000） and 25.0%, 22.3%, 23.9%, and 9.8% in females （P 〈0.0001）. Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females （ both P 〈0.0001） for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2：1 for upper, middle, lower third ESCC and GCA （P〈0.0001）. For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age 〉50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist. Conclusions The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the priamry site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

Effects of nape acupuncture combined with swallowing rehabilitation on dysphagia in pseudobulbar palsy

OBJECTIVE: To evaluate the therapeutic effects of nape acupuncture combined with rehabilitative swallowing training for dysphagia caused by pseudobulbar palsy, and to compare it with rehabilitative swallowing training alone, and to observe the improvement in quality of life after the therapy.METHODS: One hundred patients were randomly divided into two groups: the rehabilitative swallowing training group(control group, n = 50) and the nape acupuncture combined with rehabilitative swallowing training group(experimental group,n = 50). Each group had 8 weeks' therapy, 5 times a week. Patients in the control group received rehabilitative swallowing training, while those in the experimental group received nape acupuncture therapy based on swallowing rehabilitation. The out-comes were assessed by the repetitive saliva-swallowing test(RSST), water swallow test(WST), standardized swallowing assessment(SSA), and a swallow quality-of-life questionnaire(SWAL-QOL). Correlations of onset age, onset frequency and lesion location with the efficacy of the acupuncture treatment were also observed.RESULTS: The scores for RSST, WST, and SSA in both groups were lower than before the therapy(P <0.001), although the changes were more marked in the experimental group than in the control group(RSST and WST, P < 0.005; SSA, P < 0.001). Both groups recorded changes in SWAL-QOL index after the therapy(P < 0.001); and the experimental group scored higher than the control group(P < 0.001). The efficacy of acupuncture was not correlated with location(P > 0.05), but was related to onset age(P < 0.05) and onset frequency(P < 0.01).CONCLUSION: Nape acupuncture combined with rehabilitative swallowing training has an effect on dysphagia caused by pseudobulbar palsy and improves quality of life.

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations:A literature reanalysis

Background:The hereditary spastic paraplegias(HSPs)are a group of clinically and genetically heterogeneous disorders.Approximately 10% of the autosomal dominant(AD)HSPs(ADHSPs)have the spastic paraplegia 3A(SPG3A)genotype which is caused by ATL1 gene mutations.Currently there are more than 60 reported ATL1 gene mutations and the genotype-phenotype correlation remains unclear.The study aims to investigate the genotypephenotype correlation in SPG3A patients.Methods:We performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting an ATL1 gene mutation.Results:Most HSPs-SPG3A patients exhibited an early age at onset(AAO)of<10 years old,and showed an autosomal dominant pure spastic paraplegia.We found that 14% of the HSPs-SPG3A patients presented complicated phenotypes,with distal atrophy being the most common complicated symptom.The AAO of each mutation group was not statistically significant(P>0.05).The mutational spectrum associated with ATL1 gene mutation is wide,and most mutations are missense mutations,but do not involve the functional motif of ATL1 gene encoded atlastin-1 protein.Conclusions:Our findings indicate that there is no clear genotype-phenotype correlation in HSPs-SPG3A patients.We also find that exons 4,7,8 and 12 are mutation hotspots in ATL1 gene.