Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

Objective:To explore the genetic basis for child with CHARGE syndrome.Methods:A child who was diagnosed at Ningbo Women and Children′s Hospital on September 29, 2022 was selected as the study subject. Relevant clinical data were collected. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child was found to harbor a de novo c. 2972T>C (p.L991S) missense variant of the CHD7 gene, which was detected in neither of her parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PM6+ PM2_Supporting+ PP2+ PP3+ PP4). Bioinformatic analysis predicted that amino acid 991 is highly conserved among various species, and a hydrogen bond has formed between Asp993 and the mutant Ser991. Conclusion:The heterozygous c. 2972T>C (p.L991S) missense variant of the CHD7 gene probably underlay the pathogenesis of CHARGE syndrome in this child. Above finding has also enriched the mutational spectrum for CHARGE syndrome.

Objective:To explore the clinical characteristics and genetic etiology of four children with Phelan-McDermid syndrome (PMS).Methods:Four children who had visited the Affiliated Women and Children′s Hospital of Ningbo University between June 2, 2022 and May 8, 2023 were selected as the study subjects. Clinical data of the children were collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and quantitative PCR (q-PCR) analysis. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:All children had presented with speech and language delays and intellectual disability. Children 3 and 4 also presented with autistic behaviors. WES showed that the children 1 and 2 had respectively carried a heterozygous c.731T>C (p.Leu244Pro) and a c.2782_2851del (p.Gly928ArgfsTer4) variant of the SHANK3 gene. Sanger sequencing confirmed that their parents did not carry the same variant, suggesting that they were de novo in origin. Children 3 and 4 had respectively harbored a 121 kb and 52.02 kb heterozygous deletion at chromosome 22q13.33, which had both encompassed the SHANK3 and ACR genes mapped to 22q13.33. q-PCR results showed that the deletion of SHANK3 and ACR genes were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 731T>C and c. 2782_2851del variants were predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PS2_Supporting), respectively. Furthermore, the 52.02 kb and 121 kb heterozygous deletions in 22q13.33 were both predicted to be pathogenic (2D+ 4C, 1.05 in score; 2D+ 4C, 1 in score). Conclusion:The four children were all diagnosed with PMS by genetic testing. Above finding has enriched the phenotypic and mutational spectrum of PMS, and provided a basis for clinical diagnosis and genetic counseling for their families.

Purpose To analyze the relationship between different molecular types and imaging manifestations of simultaneous bilateral breast cancer.Materials and Methods Eighty-one patients with simultaneous bilateral breast cancer confirmed by surgery and pathology in the Affiliated Hospital of Qingdao University from January 2016 to May 2022 were retrospectively analyzed,80 patients received mammography and 38 patients received MRI.Imaging features referred to the 5th edition of the breast imaging reporting and data system standards.Molecular typing was evaluated and classified according to the 2013 revised St.Gallen international expert consensus recommended the determination.The clinicopathological and imaging features of the index and contralateral breast cancer were compared,and the imaging features of different molecular types of the index and contralateral breast cancer were also compared.Results There were statistically significant differences in histological types and molecular typing between the index and contralateral cancers(x2=39.72,12.23,P＜0.05).Mammograph showed that the index cancer was mostly a mass(51.9％,40/77),while the contralateral cancer was mostly calcification(38.4％,28/73);the index cancer was mostly polymorphic calcification(68.8％,22/32),while the contralateral cancer was mostly amorphous calcification(45.2％,19/42)(x2=33.15,10.47,P＜0.05).There was a statistically significant difference in the MRI enhancement between the index cancer and the contralateral cancer(x2=6.79,P＜0.05).For contralateral cancer,mammograms showed statistically significant differences in the four molecular subtypes on tumor density,as well as MRI enhancement patterns,early enhancement degree,and time-signal intensity curve(x2=26.72,7.49,8.95,13.44,12.85,P＜0.05).There was a significant difference in the distribution of calcification among the four molecular subtypes on the X-ray of the first cancer(x2=20.15,P＜0.05).Conclusion The molecular typing and some imaging characteristics of simultaneous bilateral breast cancer are different,and some imaging characteristics can provide reference for predicting the molecular typing of simultaneous bilateral breast cancer.

Background and purpose:The Shanghai Municipal Center for Disease Control and Prevention provides annual updates on cancer occurrence and trends in Shanghai.This study aimed to investigate the cancer incidence and mortality in 201 7 and their trends from 2002 to 2017 in Shanghai. Methods:Data of new cancer diagnoses and deaths from 2002 to 2017 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Cancer incidence and mortality stratified by year of diagnosis or death,gender and age group were analyzed.Number,proportion,crude rate,age-specific rate,age-standardized rate and others were calculated.The number,proportion and rates of common cancers in different groups were also calculated.Trends in age-standardized rate of incidence and death rates for all cancers combined and for the common cancer types by gender were estimated by joinpoint analysis and characterized by the annual percent change(APC)and average annual percent change(AAPC).Segi's 1960 world standard population was used for calculating age-standardized incidence and mortality. Results:The new cancer cases and deaths were 79 378 and 37 186 in Shanghai in 2017.The crude rate of incidence was 546.55/105,and the age-standardized rate was 246.31/105.The age-standardized rate of incidence was higher among females than among males.The crude rate of mortality was 256.04/1 05,and the age-standardized rate was 88.41/105.The age-standardized rate of mortality was higher among males than among females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among males reached the peak at the age groups of 60-64 years and older than 85 years,and those of mortality among females reached the peak at the age groups of older than 85 years,respectively.The sites of top 10 common cancer types sorted by the number of incidence cases among males were lung,colorectum,stomach,prostate,liver,thyroid,pancreas,bladder,kidney and oesophagus,and among females were lung,breast,thyroid,colorectum,stomach,pancreas,liver,brain,central nervous system(CNS),cervix uteri and gallbladder,the sites of those sorted by the number of deaths among males were lung,stomach,colorectum,liver,pancreas,prostate,oesophagus,bladder,lymphoma and gallbladder,among females were lung,colorectum,breast,stomach,pancreas,liver,gallbladder,brain,CNS,ovary and lymphoma.The top 10 common cancer types stratified by gender and the top 5 common cancer types stratified by common age groups merged of incidence and mortality had wide variations.Overall,the age-standardized rates of incidence were stable from 2002 to 2009,and increased 2.88％on average per year from 2009 to 201 7.The age-standardized rates of mortality were stable from 2002 to 2011,and decreased 2.66％on average per year from 2011 to 201 7.The trends differed by gender and cancer type. Conclusion:Lung cancer,colorectal cancer,pancreatic cancer,thyroid cancer,female breast cancer,cervical cancer and male prostate cancer are the most common cancers in Shanghai,the appropriate screening technical scheme should be formulated according to the current situation of malignant tumors in Shanghai,promote cancer opportunistic screening,promote appropriate technologies for intervention and management of cancer patients in the community,reduce the disease burden of malignant tumors.

Objective:To investigate the survival of cancer cases diagnosed during 2002-2013 in Shanghai. Methods:Data on new cancer cases with dead and follow-up information were obtained from the population-based cancer registry and vital statistics system of Shanghai Municipal Center for Disease Control and Prevention.Survival indicators stratified by year of diagnosis,gender,site and age were analyzed.Number of cases and proportion were calculated.The observed survival rates were calculated based on the life table.The probabilities of surviving from 0 to 99 years old were estimated according to the Elandt-Johnson model,and then the cumulative expected survival rates were calculated according to the Ederer Ⅱ method.Finally,the relative survival rates and average annual percent changes of their trends were calculated.The age-standardized relative survival rates adjusted by International Cancer Survival Standard weights were calculated. Results:Total 644 520 new cancer cases were diagnosed during 2002-2013 in Shanghai,accounting for 643 545(99.85％)cases included in the observed cohort for survival analysis.The 5-year observed survival rate increased from 37.61％to 46.47％.The 5-year relative survival rate increased from 42.1 8％to 51.11％.The 5-year age-standardized relative survival rate increased from 40.57％to 49.80％.Among the 5-year relative survival rates of cases diagnosed during 2011 to 2013,99.43％of thyroid cancer was the highest,followed by female breast cancer(88.35％)and corpus uteri cancer(85.56％);5.87％of pancreas cancer was the lowest,followed by gallbladder cancer(13.64％)and oesophagus cancer(17.72％).the rate of lung cancer with the largest number of cases was 23.59％,followed by colorectal cancer(59.82％)and stomach cancer(38.65％).The 5-year relative survival rate of total cases of all sites increased from 40.55％in 2002 to 52.77％in 2013,with an average annual percent change of 2.40％.13 cancer types showed increasing trends,such as liver cancer and lung cancer,while the trends of other cancer types were not statistically significant,such as pancreatic cancer and gallbladder cancer. Conclusion:The diagnostic levels and survival rates of cancer cases have been improved continuously in Shanghai.The trends of different cancer types were varied.

Objective:To investigate the lung cancer incidence and mortality in 2016 and their trends from 2002 to 2016 in shanghai. Methods:The data of incidence and death on lung cancer in shanghai from 2002 to 2016 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System.Lung Cancer incidence and mortality stratified by age of diagnosis or death,gender and age-group were analyzed.The number of cases and deaths,proportion,crude rates,age-specific rates,age-standardized rates,corresponding truncated age-standardized rates(35-64 years)and cumulative rates were calculated.Segi's 1960 world standard population was used for calculating age-standardized rates of incidence and mortality as well as truncated age-standardized rates.Trends in age-standardized rates of incidence and death for lung cancer in Shanghai from 2002-2016 were estimated by Joinpoint analysis and characterized by the annual percent change(APC). Results:The new lung cancer cases and deaths were 14 395 and 9 170 in Shanghai in 2016.The crude rate of incidence was 99.41/105,and the age-standardized rate of incidence was 39.76/105.New cases of lung cancer accounted for 19.34％of all malignant tumors in shanghai,ranking the first in the incidence spectrum of malignant tumors.The crude rate of mortality was 63.33/105,and the age-standardized rate was 21.57/105.Deaths of lung cancer accounted for 24.78％of all malignant tumor deaths in shanghai,ranking the first in the mortality spectrum of malignant tumors.The age-standardized rates of incidence and mortality for males were higher than those for females.The age-specific numbers and rates of incidence and mortality increased with age.The age-specific number and rate of incidence reached the peak at the age group of 60-64 years and 80-84 years respectively,and those of mortality peaked at the age group of 80-84 years and older than 85 years respectively.The incidence of lung cancer increased from 33.70/105 in 2002 to 39.76/1 05 in 2016 in Shanghai.Joinpoint analyses showed that the age-standardized rate of lung cancer incidence remained stable from 2002 to 2010(APC=-0.79,t=-1.46,P=0.175)but showed a significant upward trend with an average annual increase rate of 5.12％from 2010 to 2016(APC=5.12,t=6.97,P＜0.001).The standardized mortality showed a downward trend with an average annual decrease rate of 0.87％from 2002 to 2016(APC=-0.87,t=-2.87,P=0.013). Conclusion:The incidence of lung cancer in Shanghai during 2002-2016 presented an upward trend while the mortality of lung cancer showed a gradual downward trend.There are differences in the incidence and mortality of lung cancer among different gender and age groups.

Objective:To investigate the liver cancer incidence and mortality in 2016 and their trends during 2002 through 2016 in Shanghai. Methods:Data on new liver cancer diagnoses and deaths during 2002 through 2016 were obtained from the Shanghai Municipal Center for Disease Control and Prevention population-based cancer registry and Vital Statistics System,the numbers,crude rates and age-standardized rates of incidence and mortality of liver cancer were calculated.Segi's 1960 world standard population was used to calculate age-standardized rates.Joinpoint analysis was used to analyze the trend changes and to estimate the annual percent change of incidence and mortality rates. Results:There were 3 842 new liver cancer cases in Shanghai in 201 6,69.44％of which were males,and 3 275 deaths of liver cancer,69.44％of which were males.Mortality to incidence ratio was 0.85.The crude rate of incidence was 26.53/105,and the age-standardized rate was 10.60/105.The crude rate of mortality was 22.62/105,and the age-standardized rate was 8.65/105.The Sex ratios for age-standardized incidence and mortality were 2.91∶1 and 2.97∶1,respectively.The age-specific numbers and rates of incidence and mortality increased with age.Overall,the age-standardized rate of incidence of liver cancer was decreased 3.69％on average per year during 2002 through 2016,and the age-standardized rate of mortality of liver cancer was decreased 3.82％on average per year. Conclusion:The incidence and mortality of liver cancer in Shanghai have been remarkably decreased to a low level countrywide,while liver cancer is still one of the leading malignancies and it brings serious threat to public health,comprehensive prevention and control efforts should be strengthened according to its epidemic characteristics and risk factors.

Objective:More than half of esophageal cancer incidences and deaths occurred in China.Based on the Shanghai Tumor Registration data,this study analyzed the incidence and mortality of esophageal cancer in Shanghai in 2016 and the changing trend from 2002 to 2016,in order to provide an epidemic basis for the prevention and treatment of esophageal cancer. Methods:Data on esophageal cancer in Shanghai from 2002 to 2016 were obtained through Shanghai Municipal Center for Disease Control and Prevention Population-based Cancer Registry and Vital Statistics System.The number of cases and deaths,crude rates,composition ratios,age-specific rates and cumulative rates were counted according to the year of diagnosis or death,gender and age groups.Segi's 1960 world standard population was used to calculate age-standardized rates of incidence and mortality,and corresponding truncated age-standardized rate(35-64 years old)on esophageal cancer.Z-test and Cochran test were used to compare the differences of age-specific rates and age-standardized rates among different subgroups,respectively.Temporal trend analyses were conducted by Joinpiont 4.9.1.0 software. Results:In 2016,the proportion of morphological verification of new cases of esophageal cancer in Shanghai was 73.1 8％,the proportion of death certificate only was 0.72％,and the ratio of death to incidence was 0.84.The number of new cases and deaths of esophageal cancer in Shanghai in 2016 were 1 398 and 1 171,accounting for 1.88％and 3.1 6％of all malignant tumors,respectively.The crude incidence and mortality of esophageal cancer were 9.65/100 000 and 8.09/100000,with age-standardized incidence and mortality of 3.36/100 000 and 2.67/100,000,respectively.The age-standardized incidence and mortality were significantly higher in males than in females.The age-specific incidence and mortality increased with age,and peaked at 50.54/100 000 and 53.35/1 00 000,respectively,among people aged 85 years and older.From 2002 to 2016,both the number of new cases and deaths of esophageal cancer in Shanghai showed a downward trend,and the age-standardized incidence and mortality also showed a downward trend,with an average annual deceleration of 4.45％[annual percent change(APC)=-4.45,P＜0.001]and 4.1 7％(APC=-4.17,P＜0.001),respectively. Conclusion:The incidence and mortality of esophageal cancer in Shanghai were at a low epidemic level across China,and showed a downward trend from 2002 to 2016.Esophageal cancer screening should focus on males and subjects aged 55 to 64 years.