Objective: To investigate the clinicopathological features, immunophenotype, and genetic alterations of rectal adenocarcinoma with enteroblastic differentiation. Methods: Four cases of rectal adenocarcinoma with enteroblastic differentiation were collected at the Affiliated Hospital of Qingdao University, Qingdao, China (three cases) and Yantai Yeda Hospital of Shandong Province, China (one case) from January to December 2022. Their clinical features were summarized. Hematoxylin and eosin stain and immunohistochemical stain were performed, while next-generation sequencing was performed to reveal the genetic alterations of these cases. Results: All four patients were male with a median age of 65.5 years. The clinical manifestations were changes of stool characteristics, bloody stools and weight loss. All cases showed mixed morphology composed of conventional adenocarcinoma and adenocarcinoma with enteroblastic differentiation. Most of the tumors consisted of glands with tubular and cribriform features. In one case, almost all tumor cells were arranged in papillary structures. The tumor cells with enteroblastic differentiation were columnar, with relatively distinct cell boundaries and characteristic abundant clear cytoplasm, forming fetal gut-like glands. Immunohistochemically, the tumor cells were positive for SALL4 (4/4), Glypican-3 (3/4) and AFP (1/4, focally positive), while p53 stain showed mutated type in 2 cases. The next-generation sequencing revealed that 2 cases had TP53 gene mutation and 1 case had KRAS gene mutation. Conclusions: Rectal adenocarcinoma with enteroblastic differentiation is rare. It shows embryonal differentiation in morphology and immunohistochemistry, and should be distinguished from conventional colorectal adenocarcinoma.
Humans ; Male ; Aged ; Female ; Biomarkers, Tumor/metabolism* ; Adenocarcinoma/pathology* ; Colorectal Neoplasms ; Rectal Neoplasms/genetics* ; Cell Differentiation

Humans ; Lung Neoplasms/pathology* ; Adenocarcinoma/pathology* ; Papilloma/genetics* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Gene Amplification ; Carrier Proteins ; Cytoskeletal Proteins

Objective: To investigate the clinical, imaging, histological, and molecular features and the differential diagnosis of radiation-associated sarcomas of bone and soft tissue. Methods: Forty-six cases of radiation-associated sarcomas of the bone and soft tissue in Beijing Jishuitan Hospital from January 2010 to January 2022 were retrospectively analyzed; and the imaging, histological features and immunophenotype were examined. Results: There were 33 females and 13 males, aged from 18 to 74 years, with a mean of 52 years. The most common site of radiation-associated sarcomas were the limbs and spine (15 cases), followed by the chest (9 cases). The primary diseases included epithelial tumors (15 breast cancer, 6 cervical cancer, and 5 bowel cancer), hematolymphoid tumors, bone and soft tissue tumors and infectious lesions. The latent period of radiation-associated sarcomas ranged from 2-22 years, with an average of 11.6 years. Histopathologically, the morphology was divergent from the primary tumor. The most common malignant tumor type was undifferentiated sarcoma (22 cases), followed by osteosarcoma (16 cases). The immunophenotype of radiation-related sarcoma was almost the same as the corresponding soft tissue sarcoma. Conclusions: Radiation-induced sarcoma has a wide range of primary tumor types and its imaging, morphology and immunohistochemical features are similar to those of the primary sarcoma of bone and soft tissue. Clinical correlation is often recommended for the differential diagnosis.
Male ; Female ; Humans ; Retrospective Studies ; Sarcoma/pathology* ; Osteosarcoma/diagnostic imaging* ; Soft Tissue Neoplasms/pathology* ; Bone Neoplasms/pathology*

Animals ; Mice ; Colon ; Histological Techniques

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C₂ pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C₂ pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C₂ pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C₂ pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C₂ pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above the Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C₂ pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Glycine/analogs & derivatives* ; Humans ; Vasculitis, Leukocytoclastic, Cutaneous

Automobiles ; Hearing Loss, High-Frequency ; Hearing Loss, Noise-Induced/etiology* ; Humans ; Male ; Noise, Occupational/adverse effects* ; Occupational Diseases/epidemiology* ; Occupational Exposure

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Precision medicine became the key strategy in development priority of science and technology in China. The large population-based cohorts become valuable resources in preventing and treating major diseases in the population, which can contribute scientific evidence for personalized treatment and precise prevention. The fundamental question of the achievements above, therefore, is how to construct a large population-based cohort in a standardized way. The Chinese Preventive Medicine Association co-ordinated experienced researchers from Peking University and other well-known institutes to write up two group standards Technical specification of data processing for large population-based cohort study (T/CPMA 001-2018) and Technical specification of data security for large population-based cohort study (T/CPMA 002-2018), on data management. The standards are drafted with principles of emphasizing their scientific, normative, feasible, and generalizable nature. In these two standards, the key principles are proposed, and technical specifications are recommended in data standardization, cleansing, quality control, data integration, data privacy protection, and database security and stability management in large cohort studies. The standards aim to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence, to improve domestic scientific research level and the international influence, and to support decision-making and practice of disease prevention and control.
China ; Cohort Studies ; Delivery of Health Care ; Humans ; Population Surveillance ; Quality Control ; Reference Standards

Objective: To analyze the burden of disease (BOD) on diabetes attributable to high BMI in China from 1990 to 2016. Methods: Data based on population of the 2016 Global Burden of Disease Study for China were used to analyze the attributable fractions (PAF) of BOD for diabetes attributable to high BMI. Measurements for attributable BOD of diabetes included disability adjusted life years (DALY), years of lost life (YLL), years living with disability (YLD), death number and mortality rate. The average world population from 2010 to 2035 was used as a reference. Results: In 2016, death number of diabetes attributable to high BMI was 40 310, which was significantly higher than that in 1990 (15 008). Age-standardized death rate of diabetes attributable to high BMI increased from 2.01/100 000 in 1990 to 2.60/100 000 in 2016, which showed a more significant increasing trend in both males and people aged 15-49 years. DALYs of diabetes attributable to high BMI increased from 1.09 million person years to 3.30 million person years. YLL and YLD also showed increasing trends. The highest increasing rate of YLD was in people aged 15-49 years. High BMI was responsible for 26.01% of the diabetes deaths in 2016 in China, an increase of 39.39% compared with that in 1990 (18.66%). Most provinces in China experienced a sharp increase of DALY of diabetes attributable to high BMI from 1990 to 2016. Inner Mongolia, Xinjiang, Zhejiang, Macao SAR, Sichuan and Qinghai had the most significant increase tendency in terms of DALY rate during this period. Conclusions: There was a rapid increase of the deaths and mortality rate of diabetes attributable to high BMI, causing a heavy disease burden, in China from 1990 to 2016. The BOD varied in both different age and gender groups. More attention should be paid to males and people aged 15-49 years in the prevention and control programs of diabetes.
Adolescent ; Adult ; Body Mass Index ; China/epidemiology* ; Cost of Illness ; Diabetes Mellitus/ethnology* ; Disabled Persons ; Humans ; Macau ; Male ; Middle Aged ; Quality-Adjusted Life Years ; Sickness Impact Profile ; Young Adult