Humans ; Sarcoma, Small Cell/pathology* ; Sarcoma/pathology* ; Oncogene Proteins, Fusion ; Biomarkers, Tumor ; Soft Tissue Neoplasms/genetics*

Objective: To investigate the clinicopathological characteristics of primary pulmonary NUT carcinoma. Methods: A total of 7 cases of primary pulmonary NUT carcinoma were collected from Fujian Provincial Hospital (n=5), Fuzhou Taijiang Hospital (n=1) and Binzhou City People's Hospital of Shandong Province (n=1) from January 2021 to April 2023. The clinical, histopathological, and immunohistochemical features were analyzed, and NUT rearrangement were detected by fluorescence in situ hybridization (FISH) with break-apart probes. Results: Seven cases were all male with age ranging from 32 to 73 years. The main clinical manifestations were cough, expectoration and chest tightness. Microscopically, NUT carcinoma was composed of monotonous proliferation of primitive-appearing small-to-medium round cells, with few eosinophilic cytoplasm, arranged in solid sheets, nests or clusters. Abrupt keratinization was typically observed in 4 cases (4/7), with high mitotic activities and necrosis. Immunohistochemistry (IHC) showed that the tumors were positive for NUT (7/7), CK7 (4/4), CK5/6 (5/6), p40 (6/7). Ki-67 index were 30%-80%. NUT gene segregation (7/7) was detected by FISH break probes. Conclusions: Primary pulmonary NUT carcinoma is rare and highly malignant. Diagnosis depends on histopathology and IHC, with molecular detection as an adjunct for diagnosis. Pathologists should be aware of the clinicopathological characteristics to avoid misdiagnosis.
Adult ; Aged ; Humans ; Male ; Middle Aged ; Carcinoma/pathology* ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms/pathology* ; Neoplasm Proteins/genetics*

Arsenic/toxicity* ; Bangladesh ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Premature Birth/chemically induced* ; Rural Population ; Zinc

Adult ; Cities ; Humans ; Middle Aged ; Proportional Hazards Models ; Quality of Life ; Risk Factors ; Silicosis

To understand the mutational characteristics of ATP7B gene of hepatolenticular degeneration in Xinjiang region. 24 cases were diagnosed as hepatolenticular degeneration and the exon of ATP7B gene was detected in some of their siblings and parents. A total of 45 ATP7B gene mutations (93.75%) were detected in 24 cases, of which 14 cases were homozygous mutations or compound heterozygous mutations, six cases were heterozygous mutations and four cases were no mutations. A total of 24 gene mutations and 14 SNPS were detected, including 8 new mutations: c.251C > A, c.121A > c, c.2945C > A, c.2194C > T, c.2947T > c, c.3626T > A, c.3662_3664del, c.3557G > T. The most common mutations were c.2621C > T (p.A874V) [16.7% (4/24)] and c.2333G > T (p.R778L) [12.5% ​​(3/24)]. A total of 4 cases were diagnosed as pre-symptomatic. In this study, the most common mutation in the ATP7B gene is A874V. The most common genetic mutations in Han and Uyghur patients were different. The most common mutation in Han and Uyghur patients is R778L and A874V. Exon 11 is the gene mutations hot spot for patients with hepatolenticular degeneration in Xinjiang region, and is one of the priority exons to be detected when screening patients with suspected hepatolenticular degeneration.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203
Anisotropy ; Aspirin ; Atrophy ; Brain ; Cerebral Small Vessel Diseases ; Cognition ; Dementia ; Dementia, Vascular ; Diffusion Tensor Imaging ; Homeostasis ; Humans ; Korea ; Magnetic Resonance Imaging ; Outcome Assessment (Health Care) ; Perfusion ; Sample Size ; Stroke ; Stroke, Lacunar ; White Matter

Objective: To understand the epidemiological characteristics of scrub typhus and influencing factors in Yunnan province, and provide further information for the prevention and control of scrub typhus. Methods: Based on the incidence data of scrub typhus reported in Yunnan from 2006 to 2013, the epidemiological characteristics of scrub typhus were analyzed and related environmental factors were identified with panel negative binomial regression model. Results: A total of 8 980 scrub typhus cases were reported during 2006-2013 in Yunnan. The average annual incidence was 2.46/100 000, with an uptrend observed. Natural focus expansion was found, affecting 71.3% of the counties in 2013. The epidemic mainly occurred in summer and autumn with the incidence peak during July-October. The annual incidence was higher in females than in males. More cases occurred in children and farmers, the proportions of cases in farmers and pre-school aged children showed an obvious increase. Panel negative binomial regression model indicated that the transmission risk of scrub typhus was positive associated with monthly temperature and monthly relative humidity. Furthermore, an "U" pattern between the risk and the increased coverage of cropland and grassland as well as an "inverted-U" pattern between the risk and increased coverage of shrub were observed. Conclusion: It is necessary to strengthen the scrub typhus surveillance in warm and moist areas as well as the areas with high coverage of cropland and grassland in Yunnan, and the health education in children and farmers who are at high risk.
Child ; China/epidemiology* ; Environment ; Epidemics ; Farmers ; Female ; Humans ; Incidence ; Male ; Models, Statistical ; Orientia tsutsugamushi ; Risk Factors ; Scrub Typhus/transmission* ; Temperature

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t-test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as <0.05, no positive sites would meet this standard. When DMC CpG site cg05684382, with the smallest P value (1.26E-06) as on chromosome 12, the DVC CpG site cg26188191 with the smallest P value (6.44E-06) appeared in CMIP gene on chromosome 16. Conclusions: In this study, we analyzed the genome-wide DNA methylation and its correlation with obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.
Adolescent ; Bayes Theorem ; Beijing ; Body Weight ; Child ; DNA Methylation/genetics* ; Epigenesis, Genetic ; Female ; Genome-Wide Association Study ; Humans ; Male ; Obesity/genetics* ; Twins, Monozygotic ; Waist Circumference

Objective: To understand the survival of HIV/AIDS patients after receiving antiretroviral therapy for 10 year in Henan province and related factors. Methods: The database of national integrated management system of HIV/AIDS was used to collect the basic information and follow-up information of HIV/AIDS patients who received antiretroviral therapy between 2003 and 2005 in Henan province. Software SPSS 23.0 was used to analyze the patients' survival and related factors based on the life-table method and Cox proportional hazards model. Results: Among the 2 448 HIV/AIDS patients who started antiretroviral therapy during 2003-2005, the men accounted for 53.5%, and women accounted for 46.5%. Up to 70.1% of the patients were aged 40-59 years and 95.5% of the patients had blood borne infections. The patients were observed for 10 years after antiviral treatment, and 719 cases died from AIDS related diseases, with a mortality rate of 3.78/100 per year (719/19 010 per year). The cumulative survival rates of patients within 1-year, 3 years, 5 years and 10 years were 0.94, 0.86, 0.78, 0.69 respectively. Compared with the patients aged <40 years, the HRs of the patients aged 40-, 50-, 60- and ≥70 years were 1.417 (95%CI: 0.903-2.222), 1.834 (95%CI: 1.174-2.866), 2.422 (95%CI: 1.539-3.810) and 3.424 (95%CI: 2.053-5.709) respectively. Compared with patients with baseline CD(4+)T lymphocyte >350 unit/ul, the HRs of the patients with CD(4+)T lymphocyte <50 unit/μl, 50-199 unit/ul and 200-350 unit/ul were 7.105 (95%CI: 5.449-9.264), 4.175 (95%CI: 3.249-5.366) and 2.214 (95%CI: 1.691-2.900) respectively. Compared with the women, the HR of the men was 1.480 (95%CI: 1.273-1.172). Compared with the patients who received second line ART therapy, the HR of patients receiving no second line therapy was 11.923 (95%CI: 9.410-15.104). Conclusions: The cumulative survival rate the HIV/AIDS patients after 10 years of antiretroviral therapy reached 0.69 in Henan. Male, old age, low basic CD(4+)T lymphocyte count and receiving no second line therapy were the risk factors for long-term survival of AIDS patients.
Acquired Immunodeficiency Syndrome ; Adult ; Aged ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; China/epidemiology* ; Female ; HIV/drug effects* ; HIV Infections/mortality* ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Risk Factors ; Survival Analysis ; Survival Rate