OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Objective:To screen risk factors for ICU-acquired weakness in patients with mechanical ventilation and construct a predictive model, so as to provide a basis for the health management of patients with mechanical ventilation.Methods:Convenience sampling was used to select 312 ICU patients with mechanical ventilation admitted to the Tenth People's Hospital of Tongji University from October 2019 to August 2020 for the study. Patients were divided into training set ( n=220) and test set ( n=92) in a 7∶3 ratio. Based on machine learning algorithms, decision random forest (DRF), extremely-randomized trees (XRT) and generalized linear model (GLM) were used to construct three ICU-acquired weakness risk prediction models for patients with mechanical ventilation, respectively. The performance of the prediction model was evaluated using the area under the receiver operating characteristic curve ( AUC), the area under the precision-recall curve ( AUPRC), and the root mean square error ( RMSE) . Results:There were 7 predictors of risk of ICU-acquired weakness in patients with mechanical ventilation, including age, gender, braking, duration of mechanical ventilation, blood glucose, lactic acid, and parenteral nutrition. Test set and training set validation showed that AUC and AUPRC of GLM prediction model were greater than those of DRF, XRT prediction model. Test set validation indicated that the RMSE, logarithmic loss of GLM prediction model was less than those of DRF, XRT prediction model. Conclusions:Machine learning algorithm based GLM prediction model has good prediction performance. Healthcare professionals can construct evidence-based decisions for interventions in areas such as braking, duration of mechanical ventilation, and blood glucose management.

Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Objective:To screen risk factors for ICU-acquired weakness in patients with mechanical ventilation and construct a predictive model, so as to provide a basis for the health management of patients with mechanical ventilation.Methods:Convenience sampling was used to select 312 ICU patients with mechanical ventilation admitted to the Tenth People's Hospital of Tongji University from October 2019 to August 2020 for the study. Patients were divided into training set ( n=220) and test set ( n=92) in a 7∶3 ratio. Based on machine learning algorithms, decision random forest (DRF), extremely-randomized trees (XRT) and generalized linear model (GLM) were used to construct three ICU-acquired weakness risk prediction models for patients with mechanical ventilation, respectively. The performance of the prediction model was evaluated using the area under the receiver operating characteristic curve ( AUC), the area under the precision-recall curve ( AUPRC), and the root mean square error ( RMSE) . Results:There were 7 predictors of risk of ICU-acquired weakness in patients with mechanical ventilation, including age, gender, braking, duration of mechanical ventilation, blood glucose, lactic acid, and parenteral nutrition. Test set and training set validation showed that AUC and AUPRC of GLM prediction model were greater than those of DRF, XRT prediction model. Test set validation indicated that the RMSE, logarithmic loss of GLM prediction model was less than those of DRF, XRT prediction model. Conclusions:Machine learning algorithm based GLM prediction model has good prediction performance. Healthcare professionals can construct evidence-based decisions for interventions in areas such as braking, duration of mechanical ventilation, and blood glucose management.

Objective:To establish an indicator system of entrustable professional activities (EPAs) for entering residency, and to provide support for targeted training and ability evaluation of entering residency.Methods:Based on the existing indicator systems of EPAs for entering residency in China and globally, two rounds of Delphi consultation were performed to identify and optimize the indicators for EPAs. The scores of indicators were evaluated using means and coefficient of variation, and the degree of expert authority and Kendall's W coefficient were used to test the reliability of results.Results:A total of 17 indicators for EPAs were established, which defined the entrustable level of each EPA that residents should reach at the time of entry and at the end of the first year.Conclusions:This study preliminarily establishes an indicator system of EPAs for entering residency.

Objective:To investigate the dynamic changes of oral saliva flow, pH value, and bacterial flora before and after radiotherapy in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiotherapy, and to analyze the influencing factors of severe radioactive oral mucositis.Methods:One hundred NPC patients who received radiotherapy for the first time in the Head and Neck Radiotherapy Ward of Shandong Cancer Hospital and Institute from June 2, 2021 to December 30, 2022 were selected. Oral saliva flow, pH value and bacterial flora were measured at 5 time points, namely before radiotherapy, 15 times of radiotherapy, 35 times of radiotherapy, 1 month and 3 months after radiotherapy in patients with NPC, and the dynamic changes of 3 indicators were analyzed at each time. The factors of the occurrence of severe radioactive oral mucositis in patients with NPC were analyzed by univariate and multivariate logistic regression 15 times of radiotherapy.Results:The saliva flow of patients with NPC before radiotherapy, 15 times of radiotherapy, 35 times of radiotherapy, 1 month after and 3 months after radiotherapy were (16.51±1.29), (8.64±1.31), (5.15±1.14), (4.78±1.36) and (5.67±1.27) ml, respectively, with a statistically significant difference ( F=2 171.94, P<0.001). Oral saliva flow decreased to the lowest level 1 month after radiotherapy and then increased (all P<0.05). The pH values of patients with NPC before radiotherapy, 15 times of radiotherapy, 35 times of radiotherapy, 1 month after and 3 months after radiotherapy were 8.28±0.67, 5.87±0.53, 5.32±0.55, 6.04±0.83, 6.74±0.63, respectively, with a statistically significant difference ( F=370.43, P<0.001). The pH value decreased successively after 15 and 35 times of radiotherapy, and gradually increased 1 month and 3 months after radiotherapy (all P<0.05). There was a statistically significant difference ( χ2=18.24, P<0.001) in the detection rate of pathogenic bacteria in patients with NPC before radiotherapy (6%, 6/100), 15 times of radiotherapy (62%, 62/100), 35 times of radiotherapy (60%, 60/100), 1 month after radiotherapy (40%, 40/100) and 3 months after radiotherapy (29%, 29/100). Compared with before radiotherapy, there were statistically significant differences in the detection rates of pathogenic bacteria between 15 times of radiotherapy and 35 times of radiotherapy ( χ2=1.90, P=0.001; χ2=1.63, P=0.005). There was no statistically significant difference in the detection rate of pathogenic bacteria between 15 times of radiotherapy and 35 times of radiotherapy ( χ2=0.27, P=0.644). Compared with before radiotherapy, there was no statistically significant difference in the detection rate of pathogenic bacteria 1 month after radiotherapy and 3 months after radiotherapy ( χ2=1.30, P=0.024; χ2=0.83, P=0.149). Of 100 cases of NPC radiotherapy, 70 patients developed severe radiation oral mucositis (≥ grade 3). There were statistically significant differences in severe radioactive oral mucositis among patients with different smoking history ( χ2=8.84, P=0.003), alcohol drinking ( χ2=23.94, P<0.001), chemotherapy ( χ2=40.41, P<0.001), oral hygiene ( χ2=8.16, P=0.004), oral pH ( χ2=16.83, P<0.001) and oral pathogens ( χ2=8.80, P=0.003). Multivariate analysis showed that, alcohol drinking ( OR=2.23, 95% CI: 1.98-6.04, P=0.006), chemotherapy ( OR=3.13, 95% CI: 2.62-6.87, P<0.001) and oral pathogens ( OR=3.11, 95% CI: 1.04-9.31, P=0.043) were independent influencing factors for the occurrence of severe radioactive oral mucositis in NPC patients with radiotherapy. Conclusion:The oral saliva flow of patients with NPC decreases gradually from the beginning of radiotherapy to the lowest 1 month after radiotherapy and then increases. The pH value gradually decreases from the beginning of radiotherapy to 35 times of radiotherapy, and gradually increases from 1 month to 3 months after radiotherapy. The detection rate of pathogenic bacteria increases rapidly from the beginning of radiotherapy to 15 times of radiotherapy, and the growth rate is stable from 15 times of radiotherapy to 35 times of radiotherapy, and tended to be normal 1 month after radiotherapy. Drinking history, chemotherapy history and oral pathogens are independent risk factors influencing the occurrence of severe radioactive oral mucositis.

Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43％(43/87),higher than that of conventional MRI(30/87,34.48％,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19％(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85％,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CN Ⅸ-Ⅺ PNS in jugular foramen(P＜0.05)and CN Ⅸ-Ⅻ PNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P＜0.05),of PNS of CN Ⅲ-Ⅴ in cavernous sinus were higher than that of T2WI-FS(P＜0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P＜0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.

Objective:To explore the application effect of theory of inventive problem solving(TRIZ)in the management of loaner instruments in central sterile supply department(CSSD).Methods:TRIZ management team was set up to analyze problems in cleaning,disinfection and sterilization of loaner instruments.The invention principles of TRIZ were compared to determine targeted solutions to the corresponding problems.A total of 1,000 pieces of loaner instruments received by The Third Affiliated Hospital of Air Force Medical University were selected from January and December 2023 were selected,the 500 pieces received from January to June were managed by routine standard management mode,and the 500 pieces received from July to December were managed by the TRIZ management mode.The qualification rates of instruments cleaning,disinfection,packaging and sterilization,the incidence of adverse events,the satisfaction scores of clinical departments and assessment results of newly hired nurses of CSSD were compared between the two management modes.Results:The qualification rates of instruments cleaning,disinfection,packaging and sterilization of TRIZ management mode were 98.00%(490/500),97.20%(486/500),96.40%(482/500)and 96.00%(480/500),respectively,which were higher than those of routine standard management mode,the difference was statistically significant(x2=12.029,11.685,8.859,8.322,P<0.05).The incidence of adverse events of TRIZ management mode was 0%,the routine standard management mode was 1.20%,the difference was statistically significant(x2=6.036,P<0.05).The average scores of CSSD newly hired nurses in of theoretical knowledge,treatment process,cleaning,disinfection and sterilization and packaging of TRIZ management mode were(89.20±6.69)points,(88.47±3.48)points,(92.47±5.37)points and(92.00±5.83)points,respectively,which were higher than those of routine standard management mode,the difference was statistically significant(t=3.993,4.402,3.926,3.332,P<0.05).The satisfaction scores of clinical department personnel with instruments quality,distribution,handover,information traceability,service attitude and overall satisfaction of TRIZ management mode were(18.65±0.81)points,(18.85±1.04)points,(18.95±1.05)points,(18.40±0.75)points,(18.35±0.93)points and(93.20±1.91)points,respectively,which were higher than those of the routine standard management mode,the difference was statistically significant(t=3.599,5.889,4.851,4.865,2.075,8.723,P<0.05).Conclusion:The application of TRIZ in the management of loaner instruments in CSSD can significantly improve theoretical knowledge and practical skills of newly hired nurses in CSSD,thereby improving the qualification rates of instruments cleaning,disinfection,packaging and sterilization of loaner instruments,reducing the occurrence of instrument-related adverse events and improving satisfaction of department personnel with instruments use.

Objective:To investigate the effects of Sennoside A (SA) on the proliferation, migration, invasion, glycolysis and other malignant biological behaviors of gallbladder carcinoma cells, and to analyze the related mechanisms.Methods:Human gallbladder carcinoma cell lines, NOZ and SGC-996, were cultured in vitro and divided into control group, SA low dose group (L-SA, 25 μmol/L), SA medium dose group (M-SA, 50 μmol/L) and SA high dose group (H-SA, 100 μmol/L), and H-SA+ phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway activator 740Y-P group, respectively. The proliferation, migration, invasion, apoptosis and glycolysis of gallbladder cancer cells in each group were detected by cell counting assay, Transwell, flow cytometry and glycolysis kit. The protein levels of PI3K, p-PI3K, AKT and p-AKT were detected by Western blot assay. NOZ cells were used to construct tumor model of nude mice, and the mice were divided into saline treatment group and 10 mg/kg SA treatment group. The tumor formation ability of the two groups of mice was compared, and the expression level of Ki-67 in tumor of the two groups was detected by immunohistochemical assay.Results:Compared with control group, the proliferation, migration, invasion, glycolysis ability, the expression levels of p-PI3K and p-AKT were significantly decreased in SA treatment groups, while the apoptosis level was significantly up-regulated, all differences were statistically significant ( P<0.05). Compared with H-SA group, the proliferation, migration, invasion and glycolysis of H-SA+ 740Y-P group cells were up-regulated, while the apoptosis level was significantly decreased, all differences were statistically significant ( P<0.05). In vivo tumorigenesis experiments showed that, compared with the control group, the tumor volume of the SA-treated mice was reduced at day 28 [(1 051.32±130.29) mm 3 vs (575.07±170.54) mm 3, P=0.0003), the tumor weight was reduced [(1.04±0.24) g vs (0.58±0.13) g, P=0.0019], and the average optical density of Ki-67 expression was reduced [(77.00±7.00) vs (33.33±7.51), P=0.0018]. Conclusion:SA can inhibit the proliferation, migration, invasion and glycolysis of gallbladder carcinoma cells by regulating PI3K/AKT pathway.