Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Objective To investigate the value of multimodal MRI radiomics in predicting muscle-invasive bladder cancer.Methods A total of 178 patients with pathology diagnosis of bladder cancer were retrospectively collected,including 31 cases of muscle invasive bladder cancer(MIBC)and 147 cases of non-muscle invasive bladder cancer(NMIBC).Patients were randomly divided into training group and testing group at a ratio of 7︰3.The range of bladder tumors in T2WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images were segmented as volume of interest(VOI)by using ITK-SNAP software.Radiomics features were extracted through A.K software.The optimal radiomics features were obtained through radiomics algorithm and least absolute shrinkage and selection operator(LASSO)method.Finally,the logistic regression analysis method and random forest model method were used to construct prediction models.The performance of prediction models was evaluated by the receiver operating characteristic(ROC)curve.Results This study constructed four groups of models containing T2WI prediction model,DWI prediction model,ADC prediction model,and T2WI+DWI+ADC prediction model.The area under the curve(AUC)of T2WI,DWI,and ADC prediction models for identifying MIBC and NMIBC were separately 0.920,0.914,and 0.954 in the training group while those were respectively 0.881,0.773,and 0.871 in the testing group.There was no statistical significance between T2WI,DWI,and ADC prediction models.In training and testing groups,the AUC of T2WI+DWI+ADC prediction model were respectively 0.959 and 0.909,which were higher than the single sequence prediction model.The sensitivity and specificity of the training group were 0.905 and 0.853 and the sensitivity and specificity of the testing group were 0.778 and 0.795.Conclusion MRI radiomics prediction model can effectively differentiate MIBC and NMIBC.The T2WI+DWI+ADC prediction model shows better prediction efficiency.

Objective To evaluate the effect of different operation methods on the early swallowing function in the patients with laryngocarcinoma.Methods A total of 138 patients with the first time of open laryngectomy in this hospital from January 2021 to December 2022 were selected as the research subjects by convenience sampling method.The patients were divided into the vertical laryngeal resection group(vertical group,n=34),horizontal laryngeal partial resection(horizontal group,26 cases),suprachloroid laryngeal par-tial resection annular hyoid epiglottis fixation group(SCPL-CHEP group,n=26)and total laryngeal resection group(total laryngeal group,n=52)according to the operation methods.The Anderson Dysphagia Scale,Syd-ney Dysphagia Scale and modified swale drinking water test were used to evaluate the swallowing function on the first day of postoperative oral feeding in the patients.Results The total scores and scores of various di-mensions of the Chinese version of Anderson Dysphagia Scale,total scores and scores of various dimensions of Sydney Swallowing Scale and the results of the modified swale drinking water test had statistical differences a-mong the various groups(P＜0.01);the above indexes had statistical difference between the total laryngeal group and the other groups(P＜0.01),but the above indexes had no statistical difference between the two groups in the horizontal group,vertical group and SCPL-CHEP group(P＞0.05).Conclusion In the patients with laryngeal cancer undergoing open laryngectomy,the dysphagia is less severe during early eating after to-tal laryngectomy,which has little impact on life.

Objective:To explore the effect of gradual dural decompression(GDD)in preventing intraoperative encephalocele in severe traumatic brain injury (TBI).Methods:A retrospective case-control study was conducted to analyze the clinical data of 78 patients with severe TBI admitted to Affiliated Hospital of North Sichuan Medical College from January 2015 to October 2018, including 55 males and 23 females, aged 15-68 years with an average age of 38.2 years. Thirty-eight patients were treated by GDD (GDD group). During the operation, the hematoma was cleared by opening a window in the area with more hematoma, then gradually cleared in the area without opening a window. Finally, the dural "junction" was cut and the skull was closed quickly after covering the dural patch. The other 40 patients were operated by fast open dural (FOD) operation (FOD group). The incidence of intraoperative encephalocele, intracranial pressure data at the time, 24 hours, 72 hours and 7 days after operation, incidence of delayed intracranial hematoma and glasgow outcome score (GOS) at 3 months after operation were compared between the two groups.Results:All patients (except for 26 deaths) were followed up for 3-14 months, with an average of 8 months. None had intraoperative encephalocele in GDD group, compared to 8 patients in FOD group ( P<0.05). Intracranial pressure in GDD group was respective (18.4±3.6)mmHg, (20.4±4.0)mmHg, (27.7±4.6)mmHg and (28.3±4.5)mmHg at the time, 24 hours, 72 hours and 7 days after operation, showing no significant differences compared to FOD group [(19.1±3.4)mmHg, (20.9±3.9)mmHg, (27.0±3.5)mmHg, (27.6±3.4)mmHg, respectively] ( P>0.05). There was no significant difference in the incidence of delayed intracranial hematoma between the two groups [16% (6/38) in GDD group and 16% (5/32) in FOD group (except 8 cases of intraoperative encephalocele)] ( P>0.05). Three months after operation, the good rate of GOS score of GDD group was 61% (23/28) higher than that of FOD group [28% (11/40)], and the mortality rate of GDD group was 21% (8/38) lower than that of FOD group [45% (18/40)] ( P<0.05). There was no significant difference between the two groups in medium severe disability and plant survival rate ( P>0.05). Conclusions:For patients with severe TBI, compared with FOD, GDD is more effective in reducing the incidence of intraoperative encephalocele, improving the prognosis and decreasing mortality.

Objective:To explore the potential mechanism of sorafenib resistance associated long non-coding RNA (lncRNA-SRLR) promoted invasion and metastasis in U2OS osteosarcoma cells.Methods:We transfected U2OS cells with negative control lentivirus (LV-NC) or lncRNA-SRLR overexpressed lentivirus (LV-over/SRLR) particles. LV-NC and LV-over/SRLR stable transfected cells (U20S/NC and U20S/SRLR) were selected by primary cell culture medium containing puromycin. The mRNA expressions of lncRNA-SRLR and procollagen-lysine, procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of lncRNA-SRLR on the invasion of U2OS cells were determined by wound-healing assay and Transwell migration assay. The effect of SRLR on the interleukin-6 (IL-6) secretion of U2OS cells was evaluated by enzyme-linked immunosorbent assay (ELISA) analysis. The subcellular distribution of SRLR in U2OS cells was detected by fluorescence in situ hybridization (FISH) analysis.The expression of PLOD2 in cells was detected by immunofluorescence (IF). The expressions of PLOD2 and focal adhesion kinase (FAK)/signal transducer and activator of transcription 3 (STAT3) signal pathway related proteins in U2OS/NC and U2OS/SRLR cells were detected by western blotting.Results:qRT-PCR assay showed that mRNA expressions of lncRNA-SRLR and PLOD2 in U2OS/SRLR cells were (3 964.97±0.05) and (2.77±0.11), respectively, significantly higher than those in U2OS/NC cells ( P<0.001 or P<0.01). The results of wound-healing and Transwell migration assay showed that over-expression of SRLR markedly promoted the invasion ability of U2OS cells ( P<0.05). The result of ELISA analysis showed that the IL-6 secretions in U2OS/NC or U2OS/SRLR cells were (125.38±11.22) pg/ml or (119.97±13.43) pg/ml, without statistical significance ( P>0.05). The subcellular distribution assay revealed that lncRNA-SRLR is predominately located in the nucleus. The result of IF showed that compared with U2OS/NC cells, the expression of PLOD2 was up-regulated in U2OS/SRLR cells. The result of western blotting showed that over-expression of SRLR significantly increased the expression levels of PLOD2, phosphorylation (p)-FAK and p-STAT3 in U2OS cells ( P<0.01). Conclusion:lncRNA-SRLR promotes invasion and metastasis of osteosarcoma by activating PLOD2-FAK/STAT3 signal axis.

Objective:To explore the potential mechanism of sorafenib resistance associated long non-coding RNA (lncRNA-SRLR) promoted invasion and metastasis in U2OS osteosarcoma cells.Methods:We transfected U2OS cells with negative control lentivirus (LV-NC) or lncRNA-SRLR overexpressed lentivirus (LV-over/SRLR) particles. LV-NC and LV-over/SRLR stable transfected cells (U20S/NC and U20S/SRLR) were selected by primary cell culture medium containing puromycin. The mRNA expressions of lncRNA-SRLR and procollagen-lysine, procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of lncRNA-SRLR on the invasion of U2OS cells were determined by wound-healing assay and Transwell migration assay. The effect of SRLR on the interleukin-6 (IL-6) secretion of U2OS cells was evaluated by enzyme-linked immunosorbent assay (ELISA) analysis. The subcellular distribution of SRLR in U2OS cells was detected by fluorescence in situ hybridization (FISH) analysis.The expression of PLOD2 in cells was detected by immunofluorescence (IF). The expressions of PLOD2 and focal adhesion kinase (FAK)/signal transducer and activator of transcription 3 (STAT3) signal pathway related proteins in U2OS/NC and U2OS/SRLR cells were detected by western blotting.Results:qRT-PCR assay showed that mRNA expressions of lncRNA-SRLR and PLOD2 in U2OS/SRLR cells were (3 964.97±0.05) and (2.77±0.11), respectively, significantly higher than those in U2OS/NC cells ( P<0.001 or P<0.01). The results of wound-healing and Transwell migration assay showed that over-expression of SRLR markedly promoted the invasion ability of U2OS cells ( P<0.05). The result of ELISA analysis showed that the IL-6 secretions in U2OS/NC or U2OS/SRLR cells were (125.38±11.22) pg/ml or (119.97±13.43) pg/ml, without statistical significance ( P>0.05). The subcellular distribution assay revealed that lncRNA-SRLR is predominately located in the nucleus. The result of IF showed that compared with U2OS/NC cells, the expression of PLOD2 was up-regulated in U2OS/SRLR cells. The result of western blotting showed that over-expression of SRLR significantly increased the expression levels of PLOD2, phosphorylation (p)-FAK and p-STAT3 in U2OS cells ( P<0.01). Conclusion:lncRNA-SRLR promotes invasion and metastasis of osteosarcoma by activating PLOD2-FAK/STAT3 signal axis.

Objective To identify the role of IL-17A during respiratory syncytial virus (RSV) in-fection in a mouse model. Methods Female wild-type C57BL/6 mice and IL-17A knockout ( IL-17A-/-) mice at the age of 6 to 8 weeks were both randomly divided into two groups:control and RSV groups. Mice in the control groups were given the supernatant of Hep-2 cell culture, while those in the RSV groups were treated with RSV A2 through intranasal administration. Leukocytes in bronchoalveolar lavage fluid ( BALF) samples were counted. Left lung tissues were stained with hematoxylin and eosin ( HE ) to evaluate his-topathological scores. Airway hyperresponsiveness ( AHR) was measured by whole-body plethysmography. The concentrations of IFN-γ were determined with ELISA. RSV titers were measured by plaque assay. To assess the effects of IL-17A on IFN-γproduction and its role in RSV infection, IL-17A-/- mice were treated with exogenous recombinant murine IFN-γ or IL-17A, while wild-type mice were given IFN-γ neutralizing antibody intervention. Results The counts of inflammatory cells and neutrophils in BALF, lung tissue his-topathological scores, AHR, IFN-γlevels and virus titers of the wild-type group were higher than those of the IL-17A-/-group after RSV infection. IFN-γlevels, inflammatory cell counts in BALF, AHR and lung tissue histopathological scores were significantly increased in RSV-infected IL-17A-/- mice after the intervention of recombinant murine IL-17A or IFN-γ. RSV titers were much higher in the recombinant murine IL-17A-trea-ted group, but not affected by the recombinant murine IFN-γ intervention. Inflammatory cell counts in BALF, AHR and lung tissue histopathological scores were significantly decreased in RSV-infected wild-type mice following IFN-γ neutralizing antibody treatment, but no significant changes were found in RSV titers. Conclusions IL-17A might be involved in the pathogenesis of pulmonary diseases during RSV infection through promoting IFN-γ production and inhibiting viral clearance in mice.

Objective: To study the effects of endoscopic submucosal dissection(ESD) on long-term quality of life (QOL) and gastric function of patients with distal early gastric cancer (EGC), compared with those of surgery. Methods: Patients with EGC who received ESD or surgical resection in Peking Union Medical College Hospital over 1 year ago were selected to be followed up. QLQ-C30, SF-36, EQ-5D and dyspeptic symptom rating scale were used to evaluate QOL. Five-hour gastric emptying rate was used to evaluate distal gastric function. Electronic gastroscopy was used to observe whether the anastomotic stoma was stenotic. According to the age at resection, 1 to 1 matching was performed between the distal 1/3 gastric ESD (E_P) group and the distal subtotal gastrectomy (S_P) group, and then the QOL and gastric function between the two groups were compared. Results: Twenty-five patients were included in group E_P and group S_P respectively. According to QLQ-C30, the scores of cognitive function were 83.3 (83.3, 83.3) in group E_P and 83.3 (83.3, 100.0) in group S_P (P=0.056). The proportion of patients with symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) between the two groups were not statistically different. There was no statistical difference in the scores of EQ-5D and SF-36 between the two groups. According to dyspeptic symptom rating scale, 56.0% patients in group E_Phad burning sensation, but only 28.0% in group S_P had this symptom (P=0.054). 20.0% of patients in group S_Preported nausea, while only 4.0% in group E_P had this symptom (P=0.084). Gastric emptying results showed that the proportion of patients with abnormal 5-hour gastric emptying rate was 31.8% in group E_P, while there was no abnormal emptying in group S_P (P=0.003). Gastroscopy results showed that one patient in group E_P had pyloric stenosis, but 5-hour gastric emptying rate was normal. All anastomotic stomas in group S_p were unobstructed. Conclusion ESD and surgical resection for distal EGC show similar long-term effects on QOL of patients. But the long-term gastric emptying function may decrease after distal gastric ESD.

Objective To explore the clinical features,diagnoses,differential diagnoses and treatments of superior cerebellar artery aneurysms.Methods The clinical data of 16 patients with superior cerebellar artery aneurysms,admitted to our hospital from January 2013 to March 2018,were retrospectively collected.Their clinical manifestations,imaging features,surgical effects and related problems in the process of diagnoses and treatments were analyzed.Results Among the 16 patients,11 were caused by aneurysm rupture;8 had subarachnoid hemorrhage alone,and three had subarachnoid hemorrhage accompanied by ventricular hemorrhage;CT and CTA confirmed that 8 were superior cerebellar artery aneurysms,two were posterior cerebral artery aneurysms,and one was with unclear diagnosis.In the other 5 patients,three had eyelid ptosis and two had abducent nerve palsy;CT,CTA or MR imaging showed that two were considered as ventral brainstem occupying lesions,and three did not have clear diagnosis.Finally,all patients were diagnosed as having superior cerebellar artery aneurysms by three-dimensional DSA.Five patients were treated with interventional embolization first,and one was treated with surgical clipping because of vertebral artery stenosis and difficulty of catheter access;two patients were transferred to our department for surgical clipping due to aneurysm rupture after embolization treatment in other hospitals;and 9 patients were treated by surgical clipping directly.After treatments,one patient was in bed for a long time due to cerebellar infarction and systemic complications,and the other 15 patients recovered well;two of them underwent ventricular peritoneal shunt due to hydrocephalus.Conclusions Superior cerebellar artery aneurysm has onset of subarachnoid hemorrhage mostly,and oculomotor and abductor nerve paralysis,and space occupying manifestation around the brainstem sometimes.For patients with suspicious posterior circulation aneurysms whose diagnosis or location are unclear,three-dimensional DSA examination should be performed early to confirm the diagnosis.Treatment should be taken as soon as possible once the superior cerebellar artery aneurysm is defined.Interventional embolization may be the first choice,but it is necessary to master the methods of surgical clipping in order to treat the disease timely.

OBJECTIVE To investigate the clinical significance of microcalcification under high resolution ultrasonography in predicting thyroid micropapillary carcinoma(PTMC) and cervical lymph node metastasis. METHODS The clinical data of 388 patients with papi l lar y thyroid microcarcinoma were analyzed retrospectively in Beijing Tongren Hospital from Jan 2013 to Jun 2017, which included patients' clinical ultrasonographic features and pathological results in this study. Pearson correlation analysis and data fitting modeling were used to analyze the microcalcification, the maximum diameter of the tumor and the cervical lymph node metastasis in the central region. RESULTS The incidence of microcalcification in PTMC patients was closely related to the maximal diameter of the tumor. The tumor diameter of PTMC was related to the lymph node metastasis rate in the central region of the neck, and it was not found that microcalcification was associated with lymph node metastasis in the central region of the neck. CONCLUSION The weight of microcalcification in the diagnosis of PTMC is related to the maximum diameter of the nodule. Furthermore, patients with thyroid nodules having a tumor diameter of less than 1 cm, with the larger diameter of tumor nodules, the greater the risk of PTMC, the more recommended fine needle biopsy.