Objective To explore the differentially expressed mRNAs and related biological processes and pathways in fractional low-dose ionizing radiation (LDIR)-induced senescence of normal human bronchial epithelial (HBE) cells by high-throughput mRNA sequencing and bioinformatics techniques. Methods Senescence-associated β-galactosidase staining and senescence-associated secretion phenotype gene mRNA and protein expression levels were measured at 24 and 48 h after irradiating HBE cells 7 times at doses of 0, 50, 100, and 200 mGy, respectively. The differentially expressed genes were screened by high-throughput sequencing for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results The senescence-positive area of fractional low-dose irradiated HBE cells increased in a dose-dependent manner (P < 0.05). The mRNA levels and protein expression of transforming growth factor-β1(TGF-β1) and matrix metalloproteinase-9(MMP-9) genes were increased in the 100 mGy × 7 and 200 mGy × 7 groups at 24 and 48 h after the end of irradiation compared with the control group. High-throughput sequencing showed that there were 882, 475, and 1205 differentially expressed mRNAs in each dose group compared with the control group. GO analysis showed that the differentially expressed mRNAs in each dose group were mainly enriched in biological processes such as cell cycle regulation, regulation of nitrogen compound metabolic process, regulation of cell division and response to stimulus. KEGG analysis showed that the differentially expressed mRNAs were mainly enriched in the pathways of cell cycle, cell senescence, and ferroptosis. Conclusion Fractional LDIR induced senescence in HBE cells, and differentially expressed mRNA-associated biological processes and pathways in senescent cells are related to cell cycle and cell senescence.

Objective To investigate the effects of lowdose ionizing radiation (LDIR) on oxidative stress and damage repair in human bronchial epithelial (HBE) cells. Methods HBE cells were divided into 0, 50, 100, and 200 mGy groups, and cultured for 24 and 48 h after X-ray irradiation, respectively. The cell viability, levels of glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG), and transcriptional levels of DNA damage repair genes PPP2R2D and TP53 were measured. Results At 24 h after irradiation, there was no significant difference in the cell viability between the dose groups and the control group (P > 0.05); all dose groups had significantly increased MDA level, dose-dependently decreased GSH level, dose-dependently increased 8-OHdG level, and significantly increased mRNA level of PPP2R2D gene (all P < 0.05); the mRNA expression level of TP53 gene was significantly increased in the 50 mGy group (P < 0.05). At 48 h after irradiation, there were the highest cell viability, significantly decreased MDA and 8-OHdG levels, and significantly increased mRNA expression levels of PPP2R2D and TP53 genes in the 50 mGy group compared with the control group (all P < 0.05); the GSH level in the 100 mGy group was significantly increased (P < 0.05). Conclusion LDIR, especially radiation at 50 mGy, can affect the oxidative-antioxidant level in HBE cells and the transcript-level differential expression of DNA damage repair genes.

Objective: To investigate the spatio-temporal clustering characteristics of influenza in Yinzhou District, Ningbo City, Zhejiang Province from 2017 to 2021, so as to provide insights into prevention and control of influenza. Methods Data of influenza in Yinzhou District from 2017 to 2021 were collected from the Chinese Disease Prevention and Control Information System. The software ArcGIS 10.8 was employed for spatial autocorrelation analysis, and SaTScan 10.1 was employed for spatio-temporal scanning to analyze the temporal and spatial clustering characteristics of influenza incidence in Yinzhou District. Methods: Data of influenza in Yinzhou District from 2017 to 2021 were collected from the Chinese Disease Prevention and Control Information System. The software ArcGIS 10.8 was employed for spatial autocorrelation analysis, and SaTScan 10.1 was employed for spatio-temporal scanning to analyze the temporal and spatial clustering characteristics of influenza incidence in Yinzhou District. Results: Totally 60 543 influenza cases were reported in Yinzhou District from 2017 to 2021, with an incidence of 0.76%. The incidence of influenza peaked in December 2019 (9.35%) and January 2020 (9.28%) during the period between 2017 and 2021. Spatial autocorrelation analysis showed that there was a positive spatial correlation of influenza incidence in Yinzhou District from 2018 to 2021 (all P<0.05), and a high clustering in 2019 and 2021. Zhonghe Street showed a low-high clustering from 2017 to 2020; Jiangshan Town showed a low-high clustering in 2017 and 2020, and a high-high clustering in 2019 and 2021; Shounan Street showed a high-high clustering from 2018 to 2020; Yunlong Street showed a high-high clustering in 2021. Spatio-temporal scanning analysis showed that the class Ⅰ clusters were located in the central region which centered in Dongqianhu Town, with aggregation time in August 2017, in the northwest region with aggregation time in December and January from 2018 to 2020, and in the west region with aggregation time in August 2021. Conclusion The incidence of influenza in Yinzhou District from 2017 to 2021 showed a spatio-temporal clustering in the northwestern region in winter and summer.

More than 85% of patients with uveal melanoma (UM) carry a GNAQ or GNA11 mutation at a hotspot codon (Q209) that encodes G protein α subunit q/11 polypeptides (Gα_q/11). GNAQ/11 relies on palmitoylation for membrane association and signal transduction. Despite the palmitoylation of GNAQ/11 was discovered long before, its implication in UM remains unclear. Here, results of palmitoylation-targeted mutagenesis and chemical interference approaches revealed that the loss of GNAQ/11 palmitoylation substantially affected tumor cell proliferation and survival in UM cells. Palmitoylation inhibition through the mutation of palmitoylation sites suppressed GNAQ/11^Q209L-induced malignant transformation in NIH3T3 cells. Importantly, the palmitoylation-deficient oncogenic GNAQ/11 failed to rescue the cell death initiated by the knock down of endogenous GNAQ/11 oncogenes in UM cells, which are much more dependent on Gα_q/11 signaling for cell survival and proliferation than other melanoma cells without GNAQ/11 mutations. Furthermore, the palmitoylation inhibitor, 2-bromopalmitate, also specifically disrupted Gα_q/11 downstream signaling by interfering with the MAPK pathway and BCL2 survival pathway in GNAQ/11-mutant UM cells and showed a notable synergistic effect when applied in combination with the BCL2 inhibitor, ABT-199, in vitro. The findings validate that GNAQ/11 palmitoylation plays a critical role in UM and may serve as a promising therapeutic target for GNAQ/11-driven UM.
Humans ; Mice ; Animals ; Lipoylation ; NIH 3T3 Cells ; Uveal Neoplasms/genetics* ; Melanoma/genetics* ; Cell Proliferation ; Proto-Oncogene Proteins c-bcl-2 ; GTP-Binding Protein alpha Subunits, Gq-G11/genetics*

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

To explore the effectiveness and safety of endovascular recanalization for chronic internal carotid artery occlusion patients under Hasan classification.To evaluate the guiding value of Hasan classification for endovascular recanalization for chronic internal carotid artery occlusion.To investigate the effect of successful endovascular recanalization on systolic blood pressure.Methods We retrospectively reviewed 30 consecutive chronic internal carotid artery occlusion patients.According to Hasan classification and DSA results of our hospital，the study subjects were divided into 4 types：A，B，C and D.After admission，the rate of recanalization，perioperative complication and followup outcomes were collected.Results Among the 30 CICAO patients，83.3% were male and 16.7% were female，with an average age of （58.5±8.6） years.The success rate of endovascular recanalization in 30 patients was 63.3%.According to Hasan classification，the success rate of endovascular recanalization in type A was 81.8%，Type B 75%，Type C 50%，Type D 0%；The perioperative complications was 23.3%，9.1% for type A and 37.5% for type B，Type C 37.5%，Type D 0%，no severe stroke or death occurred during perioperative period.No related complications occurred in all patients during followup.There was statistical significance in systolic blood pressure before and after interventional recanalization in successful group （P<0.01）.There was no significant difference in preoperative and postoperative systolic blood pressure between the unsuccessful group of interventional recanalization （P>0.05）.Conclusion Interventional recanalization for CICAO patients is safe and effective according to Hasan classification criteria.This classification can screen patients suitable for interventional recanalization，predict the success rate of surgery.Successful interventional recanalization may result in a decrease in postoperative systolic blood pressure.

Objective:To investigate the clinical characteristics, treatment, and prognostic factors of pancreatic neuroendocrine tumors (pNETs) patients treated with Sunitinib.Methods:The clinical data of pNETs patients from Pfizer Drug Assistance Program of Cancer Foundation of China from April 2013 to November 2017 were retrospectively analyzed. Follow-up and statistical analysis were performed.Results:A total of 235 patients were enrolled, the patients′ overall survival time was between 4 and 252 months, the 3-years and 5-years survival rates were 73.8% and 60.8%, respectively. Univariate analysis showed that factors such as age, Ki-67 index and surgery were associated with the 3-years survival rates of pNETs patients ( P<0.05). Multivariate analysis demonstrated that the age, Ki-67 index and surgery were independent prognostic factors for pNETs patients ( P<0.05). For patients with liver metastases, univariate analysis revealed that surgery was associated with prognosis ( P<0.05). The 5-years survival rate of 124 patients with extending usage of Sunitinib was 53.3%. Conclusion:PNETs are rare tumors with atypical clinical symptoms and the patients often have metastasis at the initiate diagnosis. The age, Ki-67 index and surgery are associated with the prognosis of pNETs patients.

Objective:To investigate the clinical characteristics, treatment, and prognostic factors of pancreatic neuroendocrine tumors (pNETs) patients treated with Sunitinib.Methods:The clinical data of pNETs patients from Pfizer Drug Assistance Program of Cancer Foundation of China from April 2013 to November 2017 were retrospectively analyzed. Follow-up and statistical analysis were performed.Results:A total of 235 patients were enrolled, the patients′ overall survival time was between 4 and 252 months, the 3-years and 5-years survival rates were 73.8% and 60.8%, respectively. Univariate analysis showed that factors such as age, Ki-67 index and surgery were associated with the 3-years survival rates of pNETs patients ( P<0.05). Multivariate analysis demonstrated that the age, Ki-67 index and surgery were independent prognostic factors for pNETs patients ( P<0.05). For patients with liver metastases, univariate analysis revealed that surgery was associated with prognosis ( P<0.05). The 5-years survival rate of 124 patients with extending usage of Sunitinib was 53.3%. Conclusion:PNETs are rare tumors with atypical clinical symptoms and the patients often have metastasis at the initiate diagnosis. The age, Ki-67 index and surgery are associated with the prognosis of pNETs patients.

Abstract During the yellow fever epidemic in Angola in 2016, cases of yellow fever were reported in China for the first time. The 11 cases, all Chinese nationals returning from Angola, were identified in March and April 2016, one to two weeks after the peak of the Angolan epidemic. One patient died; the other 10 cases recovered after treatment. This paper reviews the epidemiological characteristics of the 11 yellow fever cases imported into China. It examines case detection and disease control and surveillance, and presents recommendations for further action to prevent additional importation of yellow fever into China.

This article reported a case of malignant pheochromocytoma and paraganglioma with cranial metastasis. The patient was a 25-year-old man. At the age of 10, he was diagnosed with retroperitoneal paraganglioma. He received radiotherapy after partial resection of the tumor. At the age of 15, when he consulted for headache and hypertension, a space occupying lesion was found on the right adrenal without further diagnosis and treatment. His headache and hypertension were aggravated at the age of 25. Then he visited our medical center and diagnosed with right adrenal pheochromocytoma. He undertook an operation to remove the right adrenal lesion, and his blood pressured could be controlled in the normal range with oral antihypertensive medication. One year after the surgery, a cranial lesion with positive 131I-metaiodobenzylguanidine imaging was found following the increase of norepinephrine and dopamine in both blood and urine. The diagnosis of malignant pheochromocytoma with cranial metastasis was confirmed. The cranial lesion was treated with cyberknife therapy for 4 times, and the lesion was slightly reduced. Four year after the removal of right adrenal tumor, he developed multiple bone metastasis in the right ribs and left ilium, and then he received 131I-metaiodobenzylguanidine radiotherapy. Additionally, the results of gene test indicated a pathogenic mutation of SDHB. During the follow-up period of one year after the treatment, his blood pressure fluctuated to about 140/90mmHg with 10mg of phenoxybenzamine once a day. The case is a malignant pheochromocytoma with multiple bone metastasis characterized by a long course with an ideal prognosis in a way. Consequently, we suggested the diagnostic pathway with genetic testing based on clinical phenotype to approach more timely diagnosis and reasonable evaluation of the prognosis in pheochromocytoma and paraganglioma. Furthermore, clinicians should pay more attention to the long-term surveillance.