Objective:To construct an evaluation index system of internal control medical equipment based on the internal control theory of The Committee of Sponsoring Organizations of the Treadway Commission(COSO)and combined with the current situation of medical equipment internal management in public hospitals,so as to provide reference and suggestions for the evaluation of internal control of medical equipment in public hospitals.Methods:Through literature research and expert consultation,the evaluation index system of internal control of medical equipment was preliminarily determined.Using the Delphi method,15 experts from 1 medical college and 3 tertiary hospitals in Beijing who were engaged in the use and management of medical equipment were selected to conduct two rounds of consultation on the evaluation index system of internal control of medical equipment,and the evaluation indicators were scored and screened.The analytic hierarchy process(AHP)was used to determine the index weights,and the internal control evaluation index system of medical equipment in public hospitals based on COSO was constructed.Results:The coefficient of the two rounds of expert consultation was 100%.The authority degree of consulting experts was 0.867.Finally,the evaluation index system of internal control of medical equipment in tertiary public hospitals was formed,which included 5 first-level indicators,17 second-level indicators and 50 third-level indicators.Conclusion:The evaluation index of internal control of medical equipment in public hospitals based on COSO has high expert enthusiasm,authority and coordination.The evaluation index system includes the unit level and the business level of internal control,with a wide coverage,which makes up for the limitations of traditional internal evaluation of medical equipment,which can make up for the limitations of the internal evaluation of traditional medical equipment,improve the internal control system of medical equipment in public hospitals,and optimize the medical equipment management system.

Objective:To investigate the impacts of ionizing radiation on protein expression profiles in esophageal tissues of rats using quantitative proteomics, in order to reveal the molecular mechanisms underlying the onset and development of radiation-induced esophagitis (RIE).Methods:A total of twenty-four male SD rats were divided by simple randomization into three groups: the control, 25 Gy irradiation, and 35 Gy irradiation groups, and their esophageal tissues were collected at 7 d post-irradiation to extract total protein. Then, changes in the protein expression profiles of the esophageal tissues in irradiated rats were investigated using tandem mass tag (TMT)-labeled quantitative proteomics and bioinformatics analysis. Additionally, the expressions of two key proteins, Hp and Ndufs4, were validated using immunohistochemistry and Western blot.Results:A comparison with the control group revealed a total of 847 differentially expressed proteins (DEPs; 483 up-regulated and 364 down-regulated) following 25 Gy irradiation and 699 DEPs (443 up-regulated and 256 down-regulated) following 35 Gy irradiation. Different radiation doses led to common 326 up-regulated proteins, which were mainly involved in biological processes and signaling pathways related to immune and inflammatory responses, and 210 down-regulated proteins, which were primarily involved in biological processes and signaling pathways related to energy production and metabolism. Furthermore, a total of 155 proteins were screened using a constructed protein protein interaction(PPI) network. Of these proteins, the up-regulated ones were most associated with three functional pathways, namely innate immune responses, complement and coagulation cascades, and innate immune system, while the down-regulated ones were most associated with energy acquisition via oxidizing organic compounds, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle and respiratory electron transfer. These functions were enriched with nine complement-related up-regulated and five mitochondria-related down-regulated proteins, respectively. Ionizing radiation significantly up-regulated Hp ( t = 27.94, 10.96, P<0.001) and down-regulated Ndufs4 ( t = 59.27, 54.07, P<0.001), consistent with the protein sequencing result. Conclusions:Ionizing radiation can change the protein expression profiles in the esophageal tissues of rats, and these DEPs are involved in multiple radiobiology-related functional pathways such as immune processes, inflammatory responses, and abnormal energy metabolism. Screening and validation of key proteins are helpful for identifying potential biomarkers of radiation-induced esophagitis.

【Objective】 To explore the causal association between interleukin (IL) level and constipation by using two-sample Mendelian randomization. 【Methods】 Analyses were performed based on the data from gene-wide association studies (GWAS). Both interleukin and constipation data were obtained from European populations. IL as an exposure variable was obtained from two GWAS data sets: ⅰ. from a genetic map of the human plasma proteome containing 3 301 samples; ⅱ. from a GWAS data set on 90 circulating proteins, containing 30 931 samples. Constipation as an outcome variable was obtained from two GWAS data sets: ⅰ. from Finngene, containing 26919 cases and 282235 controls; ⅱ. from UKBiobank, containing a total of 3 328 cases and 459682 controls. Single nucleotide polymorphisms strongly associated with exposure variables were used as instrumental variables, with inverse variance weighted (IVW) as the main analysis method, MR-egger regression and weighted median method as supplementary evidence for IVW results, and horizontal pleiotropy and heterogeneity were tested to ensure the stability of the results. 【Results】 In both of the two different outcome variables GWAS data, IVW analysis results showed that decreased level of IL-17 receptor C was associated with an increased risk of constipation, with ORs of 0.956 (95% CI: 0.916-0.997, P=0.036‖Finngene) and 0.998 (95% CI: 0.997-0.999, P=0.040‖ukb). Increased level of IL-18 was associated with an increased risk of constipation, with ORs of 1.055 (95% CI: 1.008-1.104, P=0.022‖Finngene) and 1.001 (95% CI: 1.000-1.002, P=0.044‖ukb); while in the Finngene data, the IVW results also suggested that increased levels of IL-2 receptor alpha subunit α and decreased levels of IL-10 and IL-17 were associated with an increased risk of constipation, with ORs of 1.054 (95% CI: 1.001-1.110, P=0.049), 0.945 (95% CI: 0.896-0.996, P=0.035) and 0.934 (95% CI: 0.896-0.997, P=0.040). 【Conclusion】 IL-17 receptor C, IL-18, IL-2 receptor alpha subunit α, IL-10, and IL-17 were causally associated with the risk of constipation.

Objective:To develop and verify a predictive model based on CT characteristics for predicting infected walled-off necrosis (IWON) in MSAP and SAP patients.Methods:The clinical and CT data of 1 322 patients diagnosed as MSAP and SAP according to the 2012 Atlanta revised diagnostic criteria in the First Affiliated Hospital of Naval Medical University from January 2015 to December 2020 were continuously collected. Finally, 126 patients who underwent enhanced CT scans within 3 days after admission and percutaneous catheter drainage of WON during hospitalization were enrolled. Among them, there were 63 MSAP and 63 SAP patients. According to the results of the culture from drainage fluid, the patients were divided into sterile walled-off necrosis group (SWON group, n=31) and infected walled-off necrosis group (IWON group, n=95). Patients were divided into training set (18 patients with SWON and 74 patients with IWON from January 2015 to December 2018) and validation set (13 patients with SWON and 21 patients with IWON from January 2019 to December 2020). Univariate and multivariate logistic regression analysis were performed to establish a model for predicting IWON. The model was visualized as a nomogram. The receiver operating characteristic curve (ROC) was drawn. The predictive efficacy of the model was evaluated by the area under the curve (AUC), sensitivity, specificity and accuracy, and the clinical application value was judged by decision curve analysis (DCA). Results:Univariate regression analysis showed that age, etiology, WON with bubble sign and the lowest CT value of WON were significantly associated with IWON. Multivariate logistic regression analysis showed that older age, biliary acute pancreatitis, WON with bubble sign, and the greater minimum CT value of WON were independent predictors for IWON. The formula for the prediction model was 0.12+ 0.01 age-0.75 hyperlipidemia-1.62 alcoholic-2.62 other causes+ 19.18 WON bubble sign+ 0.10 minimum CT value of WON. The AUC, sensitivity, specificity, and accuracy of the model were 0.85 (95% CI 0.76-0.94), 67.57%, 88.89%, and 71.74% in the training set and 0.78(95% CI0.62-0.94), 66.67%, 84.62%, and 73.53% in the validation set, respectively. The decision analysis curve showed that when the nomogram differentiated IWON from SWON at a rate greater than 0.38, using the nomogram could benefit the patients. Conclusions:The prediction model established based on CT characteristics might non-invasively and accurately predict the presence or absence of IWON in MSAP and SAP patients, and provide a basis for guiding treatment and evaluating prognosis.

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes

Objective:To investigate the MRI features of intraductal papillary mucinous tumor (IPMN) of the pancreas and establish a prediction model for predicting the malignancy risk.Methods:The clinical data of 260 IPMN patients who underwent MRI and pathological confirmed in the First Affiliated Hospital of Naval Medical University from October 2012 to April 2020 were retrospectively analyzed. According to the pathological results, all patients were divided into benign group (including IPMN with low-grade dysplasia) and malignant group (including IPMN with high grade dysplasia and invasive carcinoma). According to international consensus of prediction model modeling, patients were divided into training set and validation set in chronological order. A prediction model was developed based on a training set consisting of 193 patients (including 117 patients with benign IPMN and 76 patients with malignant IPMN) between October 2012 and April 2019, and the model was validated in 67 patients (including 40 patients with benign IPMN and 27 patients with malignant IPMN) between May 2019 and April 2020. The multivariable logistic regression model was adopted to identify the independent predictive factors for IPMN malignancy and establish and visualized a nomogram. The ROC was drawn and AUC was calculated. The decision curve analysis was used to evaluate its clinical usefulness.Results:The IPMN type, cyst size, thickened cyst wall, mural nodule size, diameter of main pancreatic duct (MPD) and the abrupt change in the caliber of the MPD with distal pancreatic atrophy in the training set and validation set, and jaundice and lymphadenopathy in the training set were significantly different between benign group and malignant group ( P<0.05). The multivariable logistic regression model of characteristics included the jaundice, cyst size, mural nodule size ≥5 mm, the abrupt change in caliber of the MPD with distal pancreatic atrophy were independent risk factors for IPMN maligancy. The model for predicting IPMN malignancy was -0.35+ 2.28×(jaundice)+ 1.57×(mural nodule size ≥5 mm)+ 2.92×(the abrupt change in caliber of the MPD with distal pancreatic atrophy)-1.95×(cyst <3 cm)-1.05×(cyst≥3 cm). The individualized prediction nomogram using these predictors of the malignant IPMN achieved an AUC of 0.85 (95% CI 0.79-0.91) in the training set and 0.84 (95% CI 0.74-0.94) in the validation set. The sensitivity, specificity and accuracy of the training set were 72.37%, 85.47% and 80.31%, respectively. The sensitivity, specificity and accuracy of the validation set were 81.48%, 75.00% and 77.61%, respectively. The decision curve analysis demonstrated that when the IPMN malignancy rate was >0.16, the nomogram diagnosing IPMN could benefit patients more than the strategy of considering all the patients as malignancy or non-malignancy. Conclusions:The nomogram based on MRI features can accurately predict the risk of malignant IPMN, and can be used as an effective predictive tool to provide more accurate information for personalized diagnosis and treatment of patients.

Objective:To develop a visualized nomogram with a predictive value to differentiate mass-forming chronic pancreatitis (MFCP) from pancreatic ductal adenocarcinoma (PDAC) patients with chronic pancreatitis (CP) history.Methods:The clinical and radiological data of 5 433 CP patients acoording to the Asia-Pacific Diagnostic Criteria between February 2011 and February 2021 in the First Affiliated Hospital of Naval Medical University were retrospectively analyzed, and 71 PDAC patients with CP history and 67 MFCP who underwent surgery or biopsy and pathologically confirmed were eventually enrolled. The training set included 44 patients with MFCP and 59 patients with PDAC who were diagnosed between February 2011 and April 2018. The validation set consisted of 23 patients with MFCP and 12 patients with PDAC who were diagnosed between May 2018 and February 2021. Univariate and multivariate logistic regression analyses were performed to develop a prediction model for PDAC and MFCP, and the model was visualized as a nomogram. ROC was used to evaluate the predictive efficacy of the nomogram, and the clinical usefulness was judged by decision curve analysis.Results:The univariate analysis showed that a significant association with pancreatic cancer were observed for the duct-to-parenchyma ratio ≥0.34, pancreatic duct cut-off, pancreatic portal hypertension, arterial CT attenuation, portal venous CT attenuation, delayed CT attenuation, and vascular invasion in both the training and validation cohorts, but the duct-penetrating sign in the training cohort only. The multivariable logistic regression analysis showed that statistically significant differences (all P value <0.05) existed in cystic degeneration, a duct-to-parenchyma ratio ≥0.34, the duct-penetrating sign, pancreatic portal hypertension and arterial CT attenuation between the two cohorts. The above parameters were selected for the logistic regression model. The predicted model=3.65-2.59×cystic degeneration+ 1.26×duct-to-parenchyma ratio≥0.34-1.40×duct-penetrating sign+ 1.36×pancreatic portal hypertension-0.05×arterial CT attenuation. Area under the curve, sensitivity, specificity and accuracy of the model-based nomogram were 0.87 (95 CI 0.80-0.94), 89.0%, 75.0% and 83.5% in the training cohort, and 0.94 (95 CI 0.82-0.99), 91.7%, 100% and 97.1% in the validation cohort, respectively. Decision curve analysis showed that when the nomogram differentiated MFCP from PDAC patients with CP history at a rate of 0.05-0.85, the application of the nomogram could benefit the patients. Conclusions:The nomogram based on CT radiological features accurately differentiated MFCP from PDAC patients with CP history and provide reference for guiding the treatment and judging the prognosis.

Objective:To develop and validate a visualized computed tomography nomogram for differentiating focal-type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC).Methods:This retrospective review included 42 consecutive patients with fAIP diagnosed according to the International Consensus Diagnostic Criteria and 242 consecutive patients with PDAC confirmed by pathology between January 2011 and December 2018 in the First Affiliated Hospital of Naval Medical University. Among them, 209 consecutive patients (25 fAIP and 184 PDAC) were enrolled in the development cohort; Seventy-five consecutive patients (17 fAIP and 58 PDAC) were enrolled in the validation cohort. CT image characteristics, including lesion location, size, enhancement mode and degree of mass enhancement in portal vein phase, pancreatic parenchymal atrophy, main pancreatic duct dilation, common bile duct dilation, cyst, acute obstructive pancreatitis, and vascular invasion were compared. Univariate and multivariate analysis were used to screen the independent predictive factors for fAIP and PDAC, based on which the nomogram was constructed and visualized. The receiver operating characteristic curve (ROC) was drawn and area under the curve (AUC) was calculated to evaluate the differential efficacy of the nomogram. The clinical usefulness of the nomogram was evaluated by decision curve analysis.Results:There were statistically significant differences on common bile duct dilation and the mode and degree of enhancement in portal phase between fAIP group and PDAC group in training set and validation set ( P<0.05). Univariate regression analysis showed that common bile duct dilation and degree of mass enhancement in portal vein were closely correlated with fAIP and PDAC phase between the two groups in training set and validation set; mass enhancement mode in portal vein phase and main pancreatic duct dilation were closely correlated with fAIP and PDAC in training set. Multivariate logistic regression analysis showed that common biliary duct dilatation ( OR=0.26, 95% CI 0.06-1.10, P=0.07), main pancreatic duct dilation ( OR=9.46, 95% CI 1.60-56.04, P<0.01) and mass mild hyper-enhancing in portal vein phase ( OR=0.003, 95% CI 0.0003-0.0278, P<0.0001) were the three independent predictors for fAIP and PDAC. Thus, the equation for predicting the probability of PDAC was 4.51-1.33× no dilatation of the common bile duct+ 2.25× the main pancreatic duct dilated-5.84× mass mild hyper-enhancing during the portal phase. The individualized prediction nomogram using these predictors of the fAIP achieved an AUC of 0.97 (95% CI 0.95-0.99) in the development set and 0.97(95% CI0.94-1.00) in the validation set. The sensitivity, specificity and accuracy of the model were 87.5%, 100% and 89% in the training set; and 94.83%, 94.12% and 94.67% in the validation set, respectively. The decision curve analysis demonstrated that the nomogram was clinically useful when the nomogram differentiated fAIP and PDAC at a rate of >0.2. Conclusions:The nomogram based on common bile duct dilation, main pancreatic duct dilation and mass enhancement in portal vein phase can be used as a useful tool for predicting fAIP and PDAC and provide valuable evidence for clinical decision.

Objective:To investigate the relationship between the perineural invasion score based on multidetector computed tomography (MDCT) and extrapancreatic perineural invasion (EPNI) in pancreatic ductal adenocarcinoma (PDAC).Methods:The clinical, radiological, and pathological data of 374 patients pathologically diagnosed as pancreatic cancer who underwent radical resection in the First Affiliated Hospital of Naval Medical University from March 2018 to May 2020 were analyzed retrospectively. Patients were divided into EPNI negative group ( n=111) and EPNI positive group (n=263) based on the pathological presence of EPNI. The perineural invasion score was performed for each patient based on radiological images. Univariate and multivariate logistic regression models were used to analyze the association between the perineural invasion score based on MDCT and EPNI in PDAC. Results:There were significant statistical differences between EPNI negative group and positive group on both pathological characteristics (T stage, N stage, invasion of common bile duct, and positive surgical margin) and radiological characteristics (tumor size, vascular invasion, lymph node metastasis, perineural invasion score based on MDCT, pancreatic border, parenchymal atrophy, invasion of duodenum, invasion of spleen and splenic vein and invasion of common bile duct) (all P value <0.05). Univariate analysis revealed that the tumor size, vascular invasion, lymph node metastasis, perineural invasion score based on MDCT, pancreatic border, pancreatic atrophy, invasion of duodenum, invasion of spleen and splenic vein and invasion of common bile duct were independently associated with EPNI. Multivariate analyses revealed that the perineural invasion based on MDCT was an independent risk factor for EPNI in pancreatic cancer (score=1, OR=2.93, 95% CI 1.61-5.32, P<0.001; score=2, OR=5.92, 95% CI 2.68-13.10, P<0.001). Conclusions:The perineural invasion score based on MDCT was an independent risk factor for EPNI in pancreatic cancer and can be used as an evaluation indicator for preoperative prediction of EPNI in PDAC.

Objective:To explore the differential diagnosis of pancreatic acinar cell carcinoma (PACC) and pancreatic ductal adenocarcinoma (PDAC) based on multidetector computed tomography (MDCT) features.Methods:The clinical, pathological and MDCT imaging data of 26 patients with pathologically confirmed PACC and 145 patients with pathologically confirmed PDAC who underwent MDCT from November 2013 to April 2021 were retrospectively studied. The differences of MDCT features including tumor location, tumor size, common pancreatic duct and bile duct dilatation, pancreatitis, lymph node metastasis, cyst, pancreatic parenchyma atrophy, duodenal involvement, bile ductal and vascular involvement between the two groups were compared. Univariate analysis and multivariate analysis by logistic regression models were performed to identify the independent predictive factors for PACC.Results:The tumor size, bile duct dilatation, lymph node metastasis, pancreatic parenchyma atrophy and vascular involvement were significantly different between PACC group and PDAC group (all P value<0.05). Multivariate analysis revealed that the tumor size ( OR=1.07, 95% CI 1.028-1.15, P=0.001), lymph node metastasis ( OR=0.23, 95% CI 0.065-0.800, P=0.02), pancreatic parenchyma atrophy ( OR=0.15, 95% CI 0.048-0.490, P=0.002) were closely associated with PACC. Conclusions:The tumor size, bile duct dilatation, lymph node metastasis, pancreatic parenchyma atrophy and vascular involvement evaluated by MDCT had a certain value in differentiating PACC from PDAC, and the tumor size, lymph node metastasis and pancreatic parenchyma atrophy were independent predictors for the diagnosis of PACC.