OBJECTIVE: To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously. METHODS: Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01). RESULTS: Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c.1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright's hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C (p.Met1?) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. CONCLUSION When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of co-morbid genetic diseases.
Child, Preschool ; Female ; Humans ; Male ; Class Ia Phosphatidylinositol 3-Kinase/genetics* ; Comorbidity ; Exome Sequencing ; Mutation ; Rare Diseases/genetics* ; Retrospective Studies ; Adolescent

Objective:To investigate the self-perceived cognitive decline status in the community population,and to explore the association between different dietary habits and self-perceived cognitive decline.Methods:A cross-sectional study was carried out in 11 879 community residents in the three regions of Weifang,Jining,and Zoucheng in Shandong Province.The Ascertain Dementia-8 and dietary habits information questionnaire were used to assess self-perceived cognitive decline and dietary habits,and their association were analyzed using single factor and multivariate logistic regression.Results:The detection rate of self-perceived cognitive decline was 21.4％.Lo-gistic regression showed that smoking in the past was positively associated with self-perceived cognitive decline(OR=1.40,95％CI:1.14-1.73).However,intake of fruits(often,OR=0.70,95％CI:0.52-0.94;everyday,OR=0.60,95％CI:0.44-0.81),nuts(daily,OR=0.62,95％CI:0.44-0.88),mushrooms(often,OR=0.74,95％CI:0.57-0.92)and high tryptophan foods(sometimes,OR=0.79,95％CI:0.68-0.91;everyday,OR=0.54,95％CI:0.34-0.87)were negatively associated with self-perceived cognitive decline.Conclusion:Smoking history might be a risk factor for self-perceived cognitive decline,and high frequency intake of fruits,nuts,mush-rooms,and high tryptophan foods might protective factors for it.

Objective:To investigate the symptom network structure of subjective cognitive decline(SCD)and its associated factors in middle-aged and older adults.Methods:A cross-sectional study was conducted among 8,262 community residents aged 45 years and over in Shandong Province(Jining,Weifang,and Zoucheng).SCD was assessed using the 8-item Ascertain Dementia(AD8)questionnaire,while mental health status was evaluated with Patient Health Questionnaire-9 and General Anxiety Disorder-7.SPSS and R were applied to construct the SCD symptom network model and examine its association with psychological factors.Results:The prevalence of SCD was 24.53％."Difficulty using household appliances"emerged as the core symptom,with the strongest connections to"forgetting appointments"(edge=2.13)and"declining daily memory and thinking ability".Additionally,"poor self-rated mental health"was most strongly linked to"loss of interest,change in hobbies and reduced activities"(edge=0.38).Conclusion:SCD symptoms in middle-aged and older adults exhibits strong interconnections and are closely linked to the individual's mental health condition.

Objective:To investigate the comorbidity rate of chronic diseases and prevalence of depressive symptoms among the middle-aged and elderly population,and explore the association between comorbidity with-chronic disease and depressive symptoms in middle-aged and older people.Methods:A cross-sectional study was conducted in Shandong Province.A total of 9 535 middle-aged and older people aged 45 years and over were recrui-ted.General information questionnaire,the chronic disease information questionnaire and Patient Health Question-naire were used for face-to-face interview to screen symptoms and collect information.Univariate analysis and mult-ivariate logistic regression analysis were employed to explore the association between comorbidity with chronic dis-ease and depressive symptoms.Results:The prevalence of depressive symptoms among middle-aged and older peo-ple was 8.7％,while among those with comorbid chronic diseases,the prevalence of depressive symptoms was 29.6％.Respectively,demonstrating an increasing trend with the number of chronic diseases(P＜0.001).Multiva-riate analysis revealed that comorbid chronic disease(OR=1.47,95％CI:1.22-1.78)were risk factors of depres-sive symptoms.Conclusion:Middle-aged and older people with multiple chronic conditions are more likely to be di-agnosed with depressive symptoms,and the detection rate of these symptoms increases with the number of comorbid chronic conditions.Therefore,it is recommended to strengthen mental health interventions for those with multiple chronic conditions.

Objective:To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously.Methods:Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01).Results:Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c. 1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright′s hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c. 2T>C (p.Met1? ) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. Conclusion:When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of comorbid genetic diseases.

Objective:To investigate anxiety symptoms and associated factors in relocated elderly residents of new townships,and to provide evidence for prevention interventions.Methods:A cross-sectional study was conduc-ted in relocated elderly residents in new townships of three urban areas in Shandong Province from 2021 to 2023.The study instruments included Ascertain Dementia-8,Generalized Anxiety Disorder-7,self-administered de-mographic characteristics information questionnaire.Multivariate analysis of factors associated with anxiety symp-toms in elderly residents was performed using multivariate logistic regression.Results:The prevalence rate of mild anxiety symptoms was 5.8％,and the rate of moderate-to-severe anxiety symptoms was 1.3％in 3 313 resi-dents.Multivariate analysis found that self-assessed general psychological condition(OR=0.52),good family envi-ronment(OR=0.34),no self-perceived cognitive impairment(OR=0.31),no chronic diseases(OR=0.42),and only one chronic disease(OR=0.61)were protective factors for mild anxiety symptoms,and very good dietary structure(OR=2.15)and fair dietary structure(OR=2.39)were risk factors for those.Very good family environ-ment(OR=0.11)and average family environment(OR=0.16),and no self-perceived cognitive impairment(OR=0.14)were protective factors for moderate-to-severe anxiety symptoms,and 0-3 years(OR=3.24)and 4-6 years(OR=3.28)of relocation were risk factors for those.Conclusion:Family environment,dietary structure,and duration since relocation are key factors associated with anxiety symptoms among relocated elderly residents in new townships.Targeted interventions should be implemented to address their mental health needs.

Objective:To explore the association between perceived social support,TMEM161B gene rs768705 polymorphism,and their interaction with incidence of depressive symptoms in the freshmen.Methods:A total of 9928 freshmen from two medical universities were investigated at baseline and follow-up two years later during 2018-2020 by cluster sampling.A self-report demographic characteristics questionnaire was used to collect information of general demographic characteristics.Perceived Social Support Scale,Beck Depression Inventory,Beck Anxiety Inventory and Adolescent Self-Rating Life Events Check List were used to measure the level of perceived social support,depressive symptoms,anxiety symptoms and the number of negative life events of individuals.Blood sam-ples were collected and typed for DNA by professionals.Results:Family support and other support were all nega-tively associated with depressive symptoms in the freshmen(OR=0.96,95％CI:0.93-0.99;OR=0.94,95％CI:0.91-0.98).There was no correlation between friend support and depressive symptoms in the freshmen(OR=0.99,95％CI:0.95-1.02).TMEM161B gene rs768705 polymorphism(AG)was positively associated with de-pressive symptoms in the freshmen(OR=1.58,95％CI:1.12-2.23).The interactions of friend support with TMEM161B gene rs768705 polymorphism(AG)(OR=1.13,95％CI:1.02-1.26)and other support with TMEM161B gene rs768705 polymorphism(AG)(OR=1.13,95％CI:1.02-1.25)had significant effects on the incidence of depressive symptoms in the females and no significant effect in the males.Conclusion:The perceived social support,TMEM161B gene rs768705 polymorphism and their interaction are associated with influence of de-pressive symptoms,and have sex difference in the freshmen.

Objective:To investigate the impact of traumatic experiences on panic attack,depression and anxi-ety symptoms among community residents.Methods:Totally 11 280 community residents were recruited.The Com-posite International Diagnostic Interview-3.0,Patient Health Questionnaire,7-item Generalized Anxiety Disorder Scale and general information questionnaire were used for face-to-face interview to collect information.Propensity Score Matching was conducted to match 5 184 community residents for analysis.Logistic regression was employed to analyze the impact of traumatic events on panic attack,depressive symptoms,and anxiety symptoms among the study sample.Results:Traumatic events were associated with a higher likelihood of experiencing panic attack(OR=3.26,95％CI:2.26-4.70),depression symptoms(OR=1.92,95％CI:1.56-2.37)and anxiety symptoms(OR=1.57,95％CI:1.24-1.99).Conclusion:Traumatic events extensively impact the mental health of commu-nity residents.Timely psychological support and early intervention are essential to prevent mental health issues in community residents affected by trauma.

Objective:To describe the prevalence of anxiety disorders and its distribution in Inner Mongolia Autonomous Region,and to explore the relevant factors of anxiety disorders.Methods:From June 2019 to Decem-ber 2019,representative multi-stage disproportionate stratified sampling procedure was used to sample in residents aged 18 and over in the Inner Mongolia Autonomous Region.All respondents were face-to-face interviewed by trained interviewers.Composite International Diagnostic Interview-3.0(CIDI-3.0)was used to diagnose anxiety disorders according to the criteria and definition of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ).Chi-square test and multivariate logistic regression analysis were used for statistical anal-ysis.Results:Totally 12 315 people were interviewed in the survey.The weighted 12-mouth prevalence rate of any anxiety disorder was 4.64％,and the lifetime prevalence rate was 6.25％.The weighted 12-month prevalence rate of anxiety disorders was higher in female than that in male(5.38％vs.3.92％).The rate was higher in rural resi-dents than that in urban residents(5.67％vs.3.95％).The rate was higher in people with chronic diseases than that in people without chronic diseases(6.81％vs.2.29％).Logistic regression analysis showed that unmarried(OR=2.32,95％CI:1.31-4.10),separated/divorced(OR=2.49,95％CI:1.33-4.67),in debt(OR=1.55,95％CI:1.04-2.32),chronic disease(OR=2.22,95％CI:1.39-3.53),family history of anxiety disorders(OR=12.05,95％CI:8.78-16.53),poor sleep(OR=2.64,95％CI:1.97-3.54)were risk factors of occurrence of anxiety disorders,while junior high school(OR=0.65,95％CI:0.44-0.96)was protective factor of anxiety disor-ders.Conclusion:Adults with chronic diseases,poor sleep,unmarried or separated/divorced,family history of anxi-ety disorders,and financial debt are at higher risk groups of anxiety disorder in Inner Mongolia Autonomous Re-gion.

Objective:To explore relationships and differences of perceived social support and depression-anx-iety symptoms between rural-to-urban migrated residents and rural residents.Methods:A total of 5 958 rural-to-ur-ban migrated residents and 4 720 rural residents were recruited.The Patient Health Questionnaire-9,Generalized Anxiety Disorder-7,and Perceived Social Support Scale were used to assess symptoms of depression,anxiety,and social support,respectively.Network estimation,centrality and predictability measurement,accuracy and stability verification,and network comparison were conducted based on R 4.2.0 to compare the network structure differ-ences between the two groups of residents.Results:In rural-to-urban migrated residents,"lack of energy"in depres-sive symptoms and"inability to control worry"in anxiety symptoms were the nodes with the highest expected influ-ence(EI).In rural residents,"low self-evaluation"in depressive symptoms and"difficulty relaxing"in anxiety symptoms were the nodes with the highest EI.The highest node of perceived social support EI for both groups was"support from relatives/leaders."The bridge nodes were the same for rural-to-urban migrated residents and rural residents,with"be down in spirits"being the nodes with the highest bridge expected influence.The results of net-work comparison test showed that the overall network structure of rural-to-urban migrated residents and rural resi-dents was statistically different(P＜0.05).Conclusion:There are correlation and difference among depressive symptoms,anxiety symptoms,and perceived social support in rural-to-urban migrated and rural residents.