Purpose BRCA1/2 gene germline variants of the uncertain significance(VUS)are categorized into five clas-ses based on their risk levels,and three classes require regular periodic analysis due to their unclear clinical significance.The aim of this study was to investigate the influence of updating var-iation evidences on the VUS sites and guide clinical diagnosis and treatment.Methods The VUS sites in BRCA1/2 gene were analyzed.971 samples(breast or ovarian cancer)that un-derwent BRCA1/2 germline testing were stored.The VUS sites in BRCA1/2 gene were further reinterpreted by integrating the following evidences,including population frequency database,disease database,computer software prediction,co-segregation evidence,allelic evidence and population cohort evidence to determine whether the variation classification was changed.Results The number of the patients with VUS sites was 142,accounting for 14.6％(142/971).The total number of VUS sites was 128,among which the proportions of missense muta-tion,synonymous mutation,in-frame non-shifted mutation and non-coding region mutation were 70.3％,4.7％,3.1％and 21.9％,respectively.Reinterpretation of VUS sites discovered that 11.7％(15/128)of VUS sites could be downgraded to Class 2,likely benign.Conclusion With the continuous in-creasing evidences of germline variation,the variation classifica-tion of VUS sites will be changed after periodic analysis.

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

Objective:To investigate the tau deposition pattern in Alzheimer′s disease (AD) and its correlation with cognition by 18F-MK6240 PET imaging. Methods:From August 2021 to February 2022, 46 elderly people over 55 years old (16 males, 30 females; age (68.9±7.7) years) were included from outpatient and community in Shanghai. Structural brain MRI, β-amyloid (Aβ) PET imaging, tau-PET imaging and comprehensive neuropsychological tests batteries were conducted. The subjects were divided into AD group ( n=16) and normal cognition (NC) group ( n=30) according to the 2018 National Institute on aging and Alzheimer′s Association (NIA-AA) diagnostic criteria. Quantitative analysis was conducted to investigate the tau deposition pattern in AD after preprocessing 18F-MK6240 PET images with MRI images. SUV ratio (SUVR) of brain regions such as entorhinal cortex, hippocampus, parahippocampal gyrus, amygdala, insular lobe, frontal lobe, precuneus, occipital lobe, thalamus and putamen were analyzed, with cerebellum as reference region. The differences of tau deposition in brain regions between AD and NC groups were analyzed by independent-sample t test. The associations between SUVR and Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment-Basic (MoCA-B) score were analyzed by Pearson correlation analysis. Results:AD displayed a significant tau deposition in frontal lobes, temporal lobes and parietal lobes compared with NC. SUVR of brain regions in AD group were higher than those in NC group ( t values: 3.37-9.61, all P<0.05). SUVR in brain regions were negatively correlated with MMSE score ( r values: from -0.735 to -0.350, all P<0.05) and MoCA-B score ( r values: from -0.723 to -0.367, all P<0.05). Conclusion:18F-MK6240 PET can demonstrate the tau deposition in the brain of AD patients, and the tau deposition is related to cognitive function.

Objective : To investigate the status of occupational stress and analyze its influencing factors among frontline employees working in a chemical fiber manufacturing enterprise, so as to provide insights into the development of occupational stress interventions. Methods : The frontline employees working in a chemical fiber manufacturing enterprise were selected as the study subjects using a cluster sampling method in October 2018. The status of occupational stress was investigated using the Chinese version of the effort-reward imbalance ( ERI ) questionnaire. The influencing factors for occupational stress were identified using a multivariable logistic regression model. Results : A total of 1 780 questionnaires were sent out, and 1 115 valid ones ( 62.64% ) were recovered. Among the 1 115 respondents, there were 427 men ( 38.30% ) and 688 women ( 61.70% ), and 71.22% were at ages of 21 to 39 years. There were 561 respondents with < 1 year of service ( 50.31% ), and the longest length of service was 11 years. In addition, there were 1 069 respondents ( 95.87% ) exposed to high noise, and 346 respondents ( 31.03% ) were diagnosed at a high occupational-stress state and 769 ( 68.97% ) at a low state. Multivariable logistic regression analysis identified 5 years or longer of service ( OR=1.540, 95%CI: 1.057-2.245 ) and exposure to high noise ( OR=1.917, 95%CI: 1.004-3.659 ) as risk factors for occupational stress among frontline employees in the chemical fiber manufacturing enterprise. Conclusions There are 31.03% of frontline employees at a high occupational-stress state in the chemical fiber manufacturing enterprise, and a high occupational-stress state is associated with exposure to high noise and 5 years or longer of service.

Objective:To analyze the prevalence of malnutrition among human immunodeficiency virus-exposed uninfected (HEU) children and to identify the associated factors in Hunan Province.Methods:All children born to human immunodeficiency virus (HIV)-infected mothers retrieved from Information System of Prevention of Mother-to-Child Transmission of human immunodeficiency virus Management (IPMTCT) in Hunan Province between July 2013 and June 2019 were included. Information including maternal demographic characteristic, maternal comorbidities/complications, anti-retroviral therapy during pregnancy, anti-retroviral prophylaxis for children, birth weight, and disease during follow-up was collected. The length and weight of children at one, three, six, nine, 12 and 18 months of follow-up time points were detected, and the prevalences of stunting, underweight, wasting and malnutrition among HEU children were evaluated. The generalized estimating equation was used to fit the logistic regression model to analyze the associated factors for malnutrition.Results:A total of 656 HEU children were finally included. The prevalences of stunting, underweight, wasting, and malnutrition among HEU children were highest at one month of age, which were 11.9%(78/656), 9.1%(60/656), 7.0%(45/656) and 21.0%(138/656), respectively. Maternal comorbidities/complications (adjusted odds ratio (a OR)=2.30, 95% confidence interval ( CI) 1.48 to 3.58), mono/dual anti-retroviral therapy during pregnancy (a OR=2.38, 95% CI 1.54 to 3.68), birth weight <2 500 g (a OR=2.66, 95% CI 1.69 to 4.21) and disease during follow-up (a OR=1.73, 95% CI 1.10 to 2.70) were the risk factors for malnutrition among HEU children (all P<0.050). Both taking zidovudine (a OR=0.60, 95% CI 0.38 to 0.94) and nevirapine (a OR=0.31, 95% CI 0.18 to 0.52) for anti-retroviral prophylaxis were the protective factors for malnutrition among HEU children (both P<0.050). Conclusions:The prevalence of malnutrition among HEU children is high. The prevalence of malnutrition is affected by maternal comorbidities/complications, anti-retroviral therapy during pregnancy, and birth weight, diseases during follow-up and anti-retroviral prophylaxis for children.

Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.

Objective:To investigate the correlations between cerebral β-amyloid (Aβ) deposition assessed by 18F-florbetapir (AV45) PET imaging and clinical cognitive symptoms in patients with subtle cognitive decline (SCD) and mild cognitive impairment (MCI). Methods:Data of twenty-four patients (11 males, 13 females, age: (63.2±7.6) years) diagnosed as SCD ( n=15) or MCI ( n=9) from December 2018 to March 2019 in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital were collected prospectively. All patients underwent 18F-AV45 PET imaging, brain MRI T 1 scan and Mini-Mental State Examination (MMSE) within two weeks. 18F-AV45 PET images were analyzed visually (positive, mild positive, negative). After being pretreated according to the MRI, 18F-AV45 PET images were analyzed semi-quantitatively by calculating the standardized uptake value ratio (SUVR) of Aβ deposition in 8 regions of interest (ROIs; frontal lobe, lateral parietal lobe, lateral temporal lobe, medial temporal lobe, occipital lobe, basal ganglia, posterior cingulate and precuneus), with cerebellar gray matter as the reference. Partial correlation coefficients between regional SUVRs and MMSE score were calculated. Results:18F-AV45 PET imaging showed that 16 patients with positive results and 8 patients with mild positive results. MMSE score of 24 patients was 28.2±2.0, and the SUVR was 0.93-1.87. Correlation analysis revealed that Aβ deposition in frontal cortex ( r=-0.432), posterior cingulate lobe ( r=-0.434) and precuneus ( r=-0.418) was negatively correlated with MMSE score (all P<0.05); and no significant correlations between SUVR and MMSE in other brain regions were found ( r values: from -0.412 to -0.110, all P>0.05). Conclusion:18F-AV45 PET imaging can noninvasively detect brain Aβ deposition in patients, and can effectively reflect the clinical cognitive status of patients with SCD and MCI to a certain extent.

Objective: To observe the alteration of brain glucose metabolic network in patients with somatoform disorders (SFD). Methods: ¹⁸F-fluorodeoxyglucose (FDG) PET images of 18 SFD patients (10 males, 8 females; age: (39.5±12.0) years; illness duration: (3.67±3.20) years) and 21 matched healthy controls (13 males, 8 females; age: (43.9±8.4) years) in Huashan Hospital of Fudan University from October 2011 to December 2012 were enrolled to construct the brain glucose metabolic networks for 2 groups (SFD group, control group) respectively. Then the global network properties (normalized clustering coefficient, normalized shortest path length, small-worldness and global efficiency) and local parameters (clustering coefficient and betweenness centrality of the node) were calculated using the graph theory. Differences between 2 groups were compared by permutation test with 1 000 permutations. The top 20% (18/90) were classified as Hub nodes based on the results of clustering coefficient and betweenness centrality of the node. Results: Small-worldness of SFD patients was similar to that of healthy controls (σ>1). There were decreased tendency in normalized clustering coefficient and global efficiency, and increased tendency in normalized shortest path length in SFD patients, but without significant differences (P>0.05). Compared to healthy controls, the betweenness centrality of left pallidum, left amygdala, left precuneus and right angular gyrus increased (permutation test, P<0.05); the betweenness centrality of left middle temporal gyrus, right superior occipital gyrus decreased (permutation test, P<0.05); the clustering coefficients of bilateral pallidum, bilateral thalamus, and left amygdala decreased (permutation test, P<0.05). Most changed Hub nodes (16/24) belonged to limbic system. Conclusion The changes of topological properties of brain glucose metabolic network in SFD patients including the decreased tendency of small-worldness and global efficiency, as well as the altered Hub nodes, may provide valid imaging evidences for brain dysfunction of somatization symptoms.

Objective:To explore the occupational stress status and influencing factors of workers in a textile factory in Zhejiang Provice.Methods:In October 2018, 505 workers from a textile factory in Zhejiang Province were selected as research objects by convenient sampling method. A total of 505 questionnaires were distributed, 495 of which were effective and the effective recovery rate was 98.0%. Job Content Questionnaire (JCQ) and Effort Reward Imbalance Questionnaire (REI) were used to investigate textile workers' occupational stress and analyze its influencing factors. The differences of the composition ratio of different groups were tested by χ 2 test. The influencing factors such as age, gender and occupation on occupational stress were analyzed by multivariate logistic regression. Results:ERI analysis results showed that the high and low occupational stress accounted for 30.1% and 69.9%, respectively. The differences of occupational stress among workers of different job types and working ages were statistically significant ( P<0.05) . The detection rates of high occupational stress of paper workers and spinners were 47.8% (11/23) and 44.8% (30/67) , respectively, higher than other jobs. The detection rate of high occupational stress for workers with more than 5 years of service was 46.4% (13/28) . The results of JCQ analysis showed that there was no statistical significance in the differences of daily working hours and length of service between different gender, education levels, types of work patterns, and occupational stress ( P>0.05) . Job types had significant effects on the occupational stress defined by ERI ( P<0.05) , the risk of occupational stress was 2.151 times than that of the coiler. Conclusion:There are significant differences in occupational stress risk among workers of different types of work in textile industry, so different measures should be taken to prevent and control occupational stress in different jobs.