Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

Objective This study aimed to explore the relationships between residential greenness and cardiometabolic risk factors among rural adults in Xinjiang Uygur Autonomous Region(Xinjiang)and thus provide a theoretical basis and data support for improving the health of residents in this region. Methods We recruited 9,723 adult rural residents from the 51st Regiment of the Third Division of the Xinjiang Production and Construction Corps in September 2016.The normalized difference vegetation index(NDVI)was used to estimate residential greenness.The generalized linear mixed model(GLMM)was used to examine the association between residential greenness and cardiometabolic risk factors. Results Higher residential greenness was associated with lower cardiometabolic risk factor prevalence.After adjustments were made for age,sex,education,and marital status,for each interquartile range(IQR)increase of NDVI500-m,the risk of hypertension was reduced by 10.3%(OR=0.897,95%CI=0.836-0.962),the risk of obesity by 20.5%(OR=0.795,95%CI=0.695-0.910),the risk of type 2 diabetes by 15.1%(OR=0.849,95%CI=0.740-0.974),and the risk of dyslipidemia by 10.5%(OR=0.895,95%CI=0.825-0.971).Risk factor aggregation was reduced by 20.4%(OR=0.796,95%CI=0.716-0.885)for the same.Stratified analysis showed that NDVI500-m was associated more strongly with hypertension,dyslipidemia,and risk factor aggregation among male participants.The association of NDVI500-m with type 2 diabetes was stronger among participants with a higher education level.PM10 and physical activity mediated 1.9%-9.2%of the associations between NDVI500-m and obesity,dyslipidemia,and risk factor aggregation. Conclusion Higher residential greenness has a protective effect against cardiometabolic risk factors among rural residents in Xinjiang.Increasing the area of green space around residences is an effective measure to reduce the burden of cardiometabolic-related diseases among rural residents in Xinjiang.

Influenza viruses are a serious threat to human health and have a major impact on social development, making them a public health and safety hazard worldwide. Therefore, understanding the life cycle of influenza viruses can provide strategies for fighting viral infections. After influenza virus infection, host cells will defend themselves against the virus by activating the innate immune system. There is a close relationship between the virus and host factors, as host factors are required at each stage of the influenza virus life cycle and have different effects on virral proliferation. Polymerase basic protein 1 (PB1), an RNA polymerase subunit, is a key viral protein in influenza virus replication and transcription. This review summarized how different host factors interact with PB1 to regulate the replication, transmission and pathogenicity of influenza viruses, providing new ideas for the development of antiviral drugs.

Objective:To evaluate the value of synthetic MRI combined with three dimensional-arterial spin labeling (3D-ASL) imaging in the grading of diffuse glioma and its correlation with tumor cell proliferative activity (Ki-67).Methods:This study was prospective. The clinical and imaging manifestations of 66 patients with diffuse glioma who underwent synthetic MRI combined with 3D-ASL imaging from August 2020 to June 2021 in General Hospital of Ningxia Medical University were analyzed. Among 66 patients, there were 36 males and 30 females, aged 4-76 years, and divided into low grade glioma (LGG) group ( n=25) (WHO Ⅱ) and high grade glioma (HGG) group ( n=41) (WHO Ⅲ and vⅣ). T 1, T 2, proton density (PD) and cerebral blood flow (CBF) of tumor parenchyma were measured by GE ADW4.7 postprocessing software. The Ki-67 label index (Ki-67 LI) in postoperative pathological sections was detected by immunohistochemistry. Independent sample t test or Mann-Whitney U test was used to compare the differences of quantitative parameters between HGG group and LGG group. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of T 1, PD, CBF and the combination. Spearman test was used to analyze the correlation between the parameters and Ki-67 label index (LI). Results:T 1[(1 573±173)ms], PD[(86.2±2.4)pu] and CBF[(129±48)ml·100 g -1·min -1] in HGG group were significantly higher than those in LGG group [(1 376±134)ms, (83.0±2.5)pu and (77±49)ml·100g -1·min -1 respectively], and difference had statistical significance ( t=-4.86, -5.08, -4.24, P<0.01). ROC confirmed that the area under curve (AUC) of T 1, PD and CBF in differentiating HGG from LGG were 0.847, 0.843 and 0.777, respectively. In multi-parameter analysis, the combination of three parameters had the best diagnostic efficiency (AUC=0.973) and the sensitivity and specificity were 87.8% and 100%, respectively. In LGG and HGG groups, there was no correlation between T 1, T 2, PD, CBF and Ki-67 LI. In the overall cohort, T 1, PD and CBF had slight positive correlation with Ki-67 LI ( r=0.394, 0.411 and 0.406, respectively, all P<0.01). There was no correlation between T 2 and Ki-67 LI ( r=-0.100, P=0.423). Conclusion:Synthetic MRI and 3D-ASL can noninvasively evaluate the pathological grade of glioma and predict the expression of Ki-67, among which T 1 and PD are novel imaging marks.

Objective: To report the first case of lymphomatoid gastropathy in China, and to demonstrate the clinical characteristics, diagnostic approach, treatment and prognosis in this kind of patients. Methods: One patient was diagnosed as lymphomatoid gastropathy at Peking Union Medical College Hospital, and her clinical characteristics, lab data, treatment and follow-up outcomes were reviewed. Results: A case of a 51-year-old female was presented, who underwent esophagogastroduodenoscopy (EGD) due to slight epigastric discomfort. EGD revealed multiple ulcers and erosions. Biopsies showed atypical lymphocytes infiltration with CD3(+), CD56(+), CD20(-), CD8(-), TIA(+), Granzyme B(-) and Ki-67 (75%). Epstein-Barr virus-encoded RNA in situ hybridization was negative. Four months later, repeated EGD examination showed regression of the lesions without specific treatment. Conclusion Lymphomatoid gastropathy was a unique disease entity mimicking NK/T-cell lymphomas in pathology, with the quite different profile of treatment and prognosis. It’s important to consider this issue during the differential diagnosis to avoid any excessive treatment.

Objective: The clinical features and prognosis of diffuse large B-cell lymphoma (DLBCL) were analyzed to optimize the treatment. Methods: We retrospectively collected the clinical data of patients with advanced-stage DLBCL from January 2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic characteristics, clinical stage, histological diagnosis, treatment and prognostic characteristics of these patients were analyzed. Results: A total of 370 patients with median age of 55 years old were recruited in the study. The male-to-female ratio was 1.3∶1. Among the 361 patients who underwent therapy, 280 cases received chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT). The median follow-up period was 89 months, the 5-year overall survival (OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%, 87.5%, respectively. The 5-year OS rate were significantly different between chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed that the age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki-67 index, lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), international prognostic index (IPI), therapeutic manner and chemotherapy combined with rituximab were significantly associated with the prognosis of advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG PS≥1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and β2-MG, and chemotherapy without rituximab were related with the poor prognosis of patients with advanced-stage DLBCL (all P<0.05). Conclusions Chemotherapy combined with rituximab can improve the outcome of patients with advanced-stage DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5 expression, LDH, β2-MG and chemotherapy combined with rituximab are associated with the prognosis of these patients.

Objective To analyze the feasibility of incorporation of tracking visual pathway fiber bundles by diffusion tensor imaging ( DTI) in computed tomography ( CT) simulation to develop a protective radiotherapy regimen for cerebral gliomas.Methods A total of 31 patients with cerebral gliomas who were admitted to our hospital from 2013 to 2015 and planed to receive postoperative radiotherapy were enrolled as subjects.All patients underwent CT simulation, conventional or contrast-enhanced magnetic resonance imaging, and DTI.The obtained DTI images of visual pathway fiber bundles were fused with 3DT1 anatomical scans and then imported into the treatment planning system.A protective treatment plan ( setting the entire visual pathway fiber bundles as organs at risk (OARs)) and a conventional treatment plan were made for intensity-modulated radiotherapy ( IMRT) .Comparison of treatment outcomes was made by paired t test.Results There were no significant differences in the conformity index and heterogeneity index of the planning target volume between the two treatment plans ( P=0.875,0.597), both of which had sufficient radiation doses to the target volume and conventional OARs protected.For the patients undergoing the protective treatment plan, the Dmax and Dmean values were reduced to 9.01%and 9.05%, respectively, in the ipsilateral optic tract and to 17.96%and 15.52%, respectively, in the contralateral optic tract;the Dmax and Dmean values were reduced to 5.37%and 5.48%(P=0.000), respectively, in the ipsilateral optic radiation tract and to 12.89%and 11.21%( P=0.000) , respectively, in the contralateral optic radiation tract.Conclusions The protective treatment plan based on CT simulation combined with the display of visual pathway fiber bundles by DTI can reduce the radiation dose to the entire visual pathway fiber bundles, which keeps the risk of visual dysfunction after radiotherapy as low as possible.

Objective To investigate status of the intravenous use of antibiotics in outpatients and emergency patients of a tertiary first-class hospital, and provide a reference for developing management measures in next step. Methods By a retrospective method,all the prescriptions using antibiotics by intravenous administration in outpatients and emergency department patients from a tertiary first-class hospital in 2013 were extracted from the hospital information system. The categories of antimicrobial agents,proportion of intravenous use of antimicrobial drugs,ranking of the antibiotic consumption sum and defined daily dose,and the top 10 clinical departments or wards intravenously using antimicrobial drugs were chosen to analyze. The data in 2014 were extracted as a comparison. Results Outpatients and emergency department patients respectively used 8 categories 31 kinds and 8 categories 30 kinds of intravenous antimicrobial drugs, with high consumption of cephalosporins and restricted antimicrobials such as sodium cefoxitin.Intravenous use of antimicrobial drug prescription proportion in emergency department is higher than that in outpatient department. Conclusion After intervention in 2014, antibiotic consumption is effectively controlled as compared that in 2013. But management should be strengthened and appropriate interventions should be taken to ensure the use of intravenous antibiotics in a safe,effective and economical manner.