OBJECTIVE: To explore the clinical characteristics and genetic etiology of STISS syndrome (an autosomal dominant disorder characterized by ubiquitin-proteasome system dysfunction) in a child. METHODS: A child with STISS syndrome diagnosed at the Affiliated Women and Children's Hospital of Ningbo University in September 2024 due to "abnormal development of external genitalia" was selected as the study subject. Clinical data were retrospectively collected. Peripheral blood samples were obtained from the child and his family members. Following genomic DNA extraction, whole-exome sequencing (WES) and Sanger sequencing validation were carried out. Pathogenicity of the candidate variants was assessed based on the guidelines from American College of Medical Genetics and Genomics (ACMG). The study was approved by the Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: The proband, a 16-year-old boy, presented with micropenis, testicular hypoplasia, delayed sexual development, insulin resistance, diabetes mellitus, and obesity. WES revealed that he has harbored a c.934del; p.Met312TrpfsTer3 frameshifting variant of the PSMD12 gene, which was unreported previously. Sanger sequencing confirmed that the variant to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_supporting+PM6_supporting). The variant was predicted to result in a premature termination codon. Bioinformatics analysis suggested that the amino acid at position 312 is highly conserved, and the variant may therefore affect the protein structure. CONCLUSION Patients with STISS syndrome exhibit clinical features including psychomotor retardation, intellectual disability, distinctive facial features, and urogenital abnormalities. The c.934del (p.Met312TrpfsTer3) frameshift variant of the PSMD12 gene probably underlay the pathogenesis in the proband. Above finding has enriched the mutational spectrum of the PSMD12 gene.
Adolescent ; Humans ; Male ; Exome Sequencing ; Mutation ; Proteasome Endopeptidase Complex/genetics* ; Syndrome

Objective:To explore the association between cumulative blood pressure (BP) and the risk of cerebrovascular disease (CVD) in older adults.Methods:This retrospective cohort study consecutively selected 4 480 older adults who participated in the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2009 as the study subjects. The cumulative BP was calculated using the area under the curve from measurements taken at baseline (2008-2009), the first follow-up (2011), and the second follow-up (2014). The subjects were grouped with the quartiles (Q1-Q4) of cumulative systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). The Cox proportional hazards regression models were used to analyze the hazard ratios (HR) and 95% CI for the association between cumulative BP and the risk of CVD among older adults. The restricted cubic spline function was employed to examine the potential dose-response pattern between cumulative BP and the risk of CVD. Results:During a total of 40 230 person-years of follow-up, with a mean follow-up duration of (8.98±2.16) years, 768 new cases of CVD were identified. The older adults in the highest quartile (Q4) of cumulative SBP, DBP, and PP had a significantly higher risk of CVD compared to those in the lowest quartile (Q1), with a HR of 1.68 (95% CI: 1.36-2.06), 1.67 (95% CI: 1.36-2.06), and 1.52 (95% CI: 1.24-1.84), respectively (all P<0.001). For every 10 mmHg (1 mmHg=0.133 kPa)×year increase in cumulative SBP, DBP, and PP, the risk of CVD increased by 2% ( HR=1.02, 95% CI: 1.01-1.03), 3% ( HR=1.03, 95% CI: 1.01-1.05), and 2% ( HR=1.02, 95% CI: 1.01-1.03), respectively (all P<0.05). The restricted cubic spline model revealed a linear positive correlation between cumulative SBP, DBP, and PP with the risk of CVD among older adults (all P for nonlinearity>0.05). When cumulative SBP, DBP, and PP exceeded 791.9 mmHg×years, 462.9 mmHg×years, and 323.6 mmHg×years, corresponding to an average BP level of 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively, the risk of CVD began to increase. Conclusions:Elevated long-term cumulative BP may increase the risk of CVD in older adults. Caution is warranted when SBP, DBP, and PP exceed 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively.

Background and purpose:The colorectal cancer screening program for community residents in Shanghai has been implemented for 12 years since 2013.This study aimed to analyze the impact of screening on the colorectal cancer incidence,stage and survival outcomes based on their screening participation status.Methods:This study used registry-based cohort study method.The registered residents in Shanghai from 2013 to 2017 who met the screening age range were divided into screening group and non-screening group.The data of colorectal cancer cases after being included in groups were obtained from the Population Based Cancer Registry.We calculated age-standardized cumulative incidence and age-group cumulative incidence,diagnosis stage and survival rate of colorectal cancer by gender,age and year of diagnosis.We used the Joinpoint regression method to calculate the annual change percentage for cumulative incidence trend analysis.The life table method and EdererⅡ method were used to calculate the 5-year observed survival rates and expected survival rates of colorectal cancer cases.Finally the 5-year relative survival rates were obtained.Results:The study included 1 687 689 participants aged 50-74 in screening group and 4 713 307 participants in non-screening group.During a 5-year follow-up period,there were 10 333 and 20 904 new cases of colorectal cancer diagnosed in the two groups,respectively.The age-standardized 5-year cumulative incidence in the screening group was 555.33/105,with an average annual increase of 33.32%(P＜0.05).The age-standardized 5-year cumulative incidence in the non-screening group was 529.85/105,with an average annual increase of 48.13%(P＜0.05).There was no statistically significant difference between the screening group and the non-screening group in the age-standardized 5-year cumulative incidence(X=0.25,P=0.804).The lower the age group,the greater the difference between the screening group and the non-screening group in the annual average change percentage of the age-standardized cumulative incidence.The stages 0-Ⅰ of newly diagnosed colorectal cancer cases in the screening group and non-screening group accounted for 14.70%and 7.46%,respectively,with a statistically significant difference in composition between the two groups(P＜0.05).The 5-year relative survival rate of the screening group was 73.94%,while the non-screening group was 59.66%.The survival rate indicators of the former were significantly higher than those of the latter,and the difference was statistically significant.The survival rate of the former was significantly higher than that of the latter(73.94%vs 59.66%),and the difference was statistically significant(P＜0.05).The survival rate of females in both groups of cases was higher than that of males,and the survival rate decreased with increasing age-groups at diagnosis.Conclusion:With the implementation of the colorectal cancer screening program,the growth trend of the incidence rate of colorectal cancer among the screening participants has been curbed,and the early stages of colorectal cancer cases diagnosed and the 5-year survival rate were significantly improved.In order to reduce the incidence rate of colorectal cancer in the whole population,it is necessary to vigorously promote the screening coverage of the appropriate population,especially to increase the proportion of lower age groups participating in screening.We should also pay attention to the screening quality of the elderly groups and improve the compliance of colonoscopy in high-risk participants.At the same time,we should further optimize the refined management of screening for different genders,ages,and risk groups.

Background and purpose:The colorectal cancer screening program for community residents in Shanghai has been implemented for 12 years since 2013.This study aimed to analyze the impact of screening on the colorectal cancer incidence,stage and survival outcomes based on their screening participation status.Methods:This study used registry-based cohort study method.The registered residents in Shanghai from 2013 to 2017 who met the screening age range were divided into screening group and non-screening group.The data of colorectal cancer cases after being included in groups were obtained from the Population Based Cancer Registry.We calculated age-standardized cumulative incidence and age-group cumulative incidence,diagnosis stage and survival rate of colorectal cancer by gender,age and year of diagnosis.We used the Joinpoint regression method to calculate the annual change percentage for cumulative incidence trend analysis.The life table method and EdererⅡ method were used to calculate the 5-year observed survival rates and expected survival rates of colorectal cancer cases.Finally the 5-year relative survival rates were obtained.Results:The study included 1 687 689 participants aged 50-74 in screening group and 4 713 307 participants in non-screening group.During a 5-year follow-up period,there were 10 333 and 20 904 new cases of colorectal cancer diagnosed in the two groups,respectively.The age-standardized 5-year cumulative incidence in the screening group was 555.33/105,with an average annual increase of 33.32%(P＜0.05).The age-standardized 5-year cumulative incidence in the non-screening group was 529.85/105,with an average annual increase of 48.13%(P＜0.05).There was no statistically significant difference between the screening group and the non-screening group in the age-standardized 5-year cumulative incidence(X=0.25,P=0.804).The lower the age group,the greater the difference between the screening group and the non-screening group in the annual average change percentage of the age-standardized cumulative incidence.The stages 0-Ⅰ of newly diagnosed colorectal cancer cases in the screening group and non-screening group accounted for 14.70%and 7.46%,respectively,with a statistically significant difference in composition between the two groups(P＜0.05).The 5-year relative survival rate of the screening group was 73.94%,while the non-screening group was 59.66%.The survival rate indicators of the former were significantly higher than those of the latter,and the difference was statistically significant.The survival rate of the former was significantly higher than that of the latter(73.94%vs 59.66%),and the difference was statistically significant(P＜0.05).The survival rate of females in both groups of cases was higher than that of males,and the survival rate decreased with increasing age-groups at diagnosis.Conclusion:With the implementation of the colorectal cancer screening program,the growth trend of the incidence rate of colorectal cancer among the screening participants has been curbed,and the early stages of colorectal cancer cases diagnosed and the 5-year survival rate were significantly improved.In order to reduce the incidence rate of colorectal cancer in the whole population,it is necessary to vigorously promote the screening coverage of the appropriate population,especially to increase the proportion of lower age groups participating in screening.We should also pay attention to the screening quality of the elderly groups and improve the compliance of colonoscopy in high-risk participants.At the same time,we should further optimize the refined management of screening for different genders,ages,and risk groups.

Objective:To explore the association between cumulative blood pressure (BP) and the risk of cerebrovascular disease (CVD) in older adults.Methods:This retrospective cohort study consecutively selected 4 480 older adults who participated in the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2009 as the study subjects. The cumulative BP was calculated using the area under the curve from measurements taken at baseline (2008-2009), the first follow-up (2011), and the second follow-up (2014). The subjects were grouped with the quartiles (Q1-Q4) of cumulative systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP). The Cox proportional hazards regression models were used to analyze the hazard ratios (HR) and 95% CI for the association between cumulative BP and the risk of CVD among older adults. The restricted cubic spline function was employed to examine the potential dose-response pattern between cumulative BP and the risk of CVD. Results:During a total of 40 230 person-years of follow-up, with a mean follow-up duration of (8.98±2.16) years, 768 new cases of CVD were identified. The older adults in the highest quartile (Q4) of cumulative SBP, DBP, and PP had a significantly higher risk of CVD compared to those in the lowest quartile (Q1), with a HR of 1.68 (95% CI: 1.36-2.06), 1.67 (95% CI: 1.36-2.06), and 1.52 (95% CI: 1.24-1.84), respectively (all P<0.001). For every 10 mmHg (1 mmHg=0.133 kPa)×year increase in cumulative SBP, DBP, and PP, the risk of CVD increased by 2% ( HR=1.02, 95% CI: 1.01-1.03), 3% ( HR=1.03, 95% CI: 1.01-1.05), and 2% ( HR=1.02, 95% CI: 1.01-1.03), respectively (all P<0.05). The restricted cubic spline model revealed a linear positive correlation between cumulative SBP, DBP, and PP with the risk of CVD among older adults (all P for nonlinearity>0.05). When cumulative SBP, DBP, and PP exceeded 791.9 mmHg×years, 462.9 mmHg×years, and 323.6 mmHg×years, corresponding to an average BP level of 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively, the risk of CVD began to increase. Conclusions:Elevated long-term cumulative BP may increase the risk of CVD in older adults. Caution is warranted when SBP, DBP, and PP exceed 132.0 mmHg, 77.2 mmHg, and 53.9 mmHg, respectively.