Adriamycin is a widely used anti-tumor drug.Targeting mitochondrial fusion proteins/mitofusion 1/2(MFN1/2)and nuclear factor-erythroid 2-related factor 2(NRF2)can up-regulate the expression of mitochondrial fusion protein through PKCε/Stat3/MFN2,SIRT1/MFN2,AMPK/NRF2 and other signaling pathways,promote mitochondrial fusion,maintain kinetic balance and protect mitochondrial function,reduce myocardial cell apoptosis and reduce cardiac toxicity.Understanding the regulatory role and mechanism of mitochondrial fusion in doxorubicin-induced cardio toxicity will provide new strategies for the prevention and treatment of diseases.

Objective To develop a basic competency assessment scale for generalist nurse in palliative care and test its reliability and validity.Methods The pre-test scale items pool was formed after literature review,internal discussion in the group,consultation with experts and small sample pre-survey. From January to March 2021,the pre-test scale was used to investigate 1000 nurses in various wards including internal medicine,surgery,emergency,obstetrics and gynaecology,and intensive care units.The results were analyzed by SPSS software and AMOS software to undertake item analysis,exploratory factor analysis and confirmatory factor analysis to develop the final scale.Results Five common factors and 37 entries were identified by factor analysis and explained 71.031％ of the total variance.The Cronbach's α coefficient of the scale was 0.953,the split-half reliability and the test-retest reliability of the scale was 0.772 and 0.963.The confirmatory factor analysis model fitted well,with x2/df=2.57,root mean square error of approximation (RMSEA)=0.059,comparative fit index (CFI)=0.909,incremental fit index(IFI)=0.910,and Tucker-Lewis index(TLI)=0.901.Conclusion Our developed basic competency assessment scale for generalist nurse in palliative care has good reliability and validity,and can be used to evaluate the basic competency of palliative care for generalist nurses.

Objective To explore the imaging manifestations of ectopic pancreas based on endoscopic findings in order to find out the causes of miss diagnosis and to improve the diagnostic accuracy.Methods The clinical and CT imaging data of ectopic pancreas patients who underwent CT examination and confirmed by endoscopy and pathology microscopy at Air Force Medical Center from July 2018 to March 2023 were collected.Their im-aging characteristics were analyzed according to the endoscopic findings and the miss diagnosis was analyzed.Results There were 13 patients with ectopic pancreas and 3 of them had no obvious symptoms.Ten patients presented with gastrointestinal symptoms,including epigastric discomfort and pain,incomplete obstruction,and melena.Lesion sites:8 cases were located in the gastric antrum and 5 cases were located in the small in-testine.In this group,two patients showed apical erosions and glandular opening-like depressions on endoscop-ic results,but only one patient showed a"ductal sign"shown by CT scanning.None of the 13 patients in this group made ectopic pancreatic diagnosis on imaging,of which 4 were diagnosed as thickening of the gastroin-testinal tract wall,3 were diagnosed as gastrointestinal stromal tumor,3 were diagnosed as benign tumors and 3 had no obvious abnormalities.Conclusions The imaging diagnosis of ectopic pancreas should be made by closely combinating with the results of endoscopy to improve the accuracy of imaging diagnosis.CT is of great significance for the diagnosis of ectopic pancreas,and adequate preparation before gastrointestinal examination is an important step to avoid misdiagnosis.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Ardisia Crenata Radix is a traditional Chinese medicinal plant that belongs to the Myrsinaceae family,and its main active components are coumarins,saponins,flavonoids,and volatile oil.Bergenin,ardisicrenoside A,ardisicrenoside B,ardisiacripin A,ardisiacripin B,and embelin were identified as active anticancer compounds in in-depth studies into the anti-tumor effects of Ardisia Crenata Radix.They show high therapeutic potential in oral cancer,nasopharyngeal carcinoma,liver cancer,colon cancer,bladder cancer,cervical cancer,and leukemia,mainly by inducing tumor cell apoptosis,increasing tumor cytotoxicity,inhibiting cell proliferation,inhibiting tumor cell metastasis and migration,and inducing cell regulatory enzyme cascade reactions.However,most preclinical experimental data on cinnabar root's anti-tumor mechanism have not been verified in high-quality,multi-sample,and repeated randomized controlled trials,and there are a lack of clinical research data on tumor prognosis,pharmacodynamics,and pharmacokinetics.Accurate research experiments and clinical trials should be designed to further explore the pharmacological effects of Ardisia Crenata Radix.

Objective To explore the value of machine learning(ML)models based on non-contrast CT(NCCT)radiomics features for predicting the severity of acute phase traumatic brain injury(TBI).Methods Totally 600 TBI patients were retrospectively collected as observation group,other 65 TBI patients were taken as external validation set,while 50 TBI patients were prospectively enrolled as prospective validation set.Patients in observation group were divided into high-risk subgroup(n=240)and low-risk subgroup(n=360)according to Glasgow outcome scale(GOS)at discharge.The severity of acute phase TBI in observation group was assessed by doctor A and B with the same criteria,then an artificial model was established based on clinical and NCCT data at the time of first diagnosis using logistic regression(LR)method for predicting the severity of acute phase TBI.Patients in observation group were divided into training set(n=420,including 168 in high-risk subgroup and 252 in low-risk subgroup)and test set(n=180,including 72 in high-risk subgroup and 108 in low-risk subgroup)at the ratio of 7∶3.Based on NCCT of training set,radiomics features were extracted and selected,and LR,support vector machine(SVM),random forest(RF)and K-nearest neighbor(KNN)were used to establish 4 ML models.The efficacies of the above models were validated in test set,external validation set(including 34 cases of high-risk and 31 cases of low-risk TBI)and prospective validation set(including 21 cases of high-risk and 29 cases of low-risk TBI),respectively.Results The area under the curve(AUC)of doctor A and B for evaluating the severity of acute phase TBI in observation group was 0.606 and 0.771,respectively,of artificial model was 0.824.Based on NCCT in training set,6 optimal radiomics features were selected to construct LR,SVM,RF and KNN ML models,with AUC of 0.983,0.971,0.970 and 0.984 in test set,respectively,while the AUC of artificial model was 0.708.The AUC of LR,SVM,RF,KNN ML models and artificial model in external validation set was 0.879,0.881,0.984,0.863 and 0.733,while in prospective validation set was 0.984,0.873,0.982,0.897 and 0.704,respectively.Conclusion ML models based on CT radiomics could effectively predict the severity of acute phase TBI.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

OBJECTIVE: To explore the design points of a three-dimensional (3D) printed customized cementless intercalary endoprosthesis with an intra-neck curved stem and to evaluate the key points and mid-term effectiveness of its application in the reconstruction of ultrashort bone segments in the proximal femur. METHODS: Between October 2015 and January 2021, 17 patients underwent reconstruction with a 3D printed-customized cementless intercalary endoprosthesis with an intra-neck curved stem. There were 11 males and 6 females, the age ranged from 10 to 76 years, with an average of 30.1 years. There were 9 cases of osteosarcoma, 4 cases of Ewing sarcoma, 2 cases of chondrosarcoma, 1 case of liposarcoma, and 1 case of myofibroblastoma. The disease duration was 5-14 months, with an average of 9.5 months. Enneking staging included 16 cases of stage ⅡB and 1 case of stage ⅢB. The distances from the center of the femoral head to the body midline and the acetabular apex were measured preoperatively on X-ray images. Additionally, the distances from the tip of the intra-neck curved stem to the body midline and the acetabular apex were measured at immediate postoperatively and last follow-up. The neck-shaft angle was also measured preoperatively, at immediate postoperatively, and at last follow-up. The status of osseointegration at the bone-prosthesis interface and bone growth into the prosthesis surface were assessed by X-ray films, CT, and Tomosynthesis-Shimadzu metal artefact reduction technology (T-SMART). The survival status of the patients, presence of local recurrence or distant metastasis, and occurrence of postoperative complications were assessed. The recovery of lower limb function was evaluated pre- and post-operatively using the Musculoskeletal Tumor Society (MSTS) scoring system, and pain relief was evaluated using the visual analogue scale (VAS) scores. RESULTS: The patient's femoral resection length was (163.1±57.5) mm, the remaining proximal femoral length was (69.6±9.3) mm, and the percentage of femoral resection length/total femoral length was 38.7%±14.6%. All 17 patients were followed up 25-86 months with an average of 58.1 months. During the follow-up, 1 patient died of lung metastasis at 46 months postoperatively, and the remaining 16 patients survived tumor-free. There was no complication such as periprosthetic infection, delayed incision healing, aseptic loosening, prosthesis fracture, or periprosthetic fracture. No evidence of micromotion or wear around the implanted stem of the prosthesis was detected in X-ray and T-SMART evaluations. There was no significant radiolucent lines, and radiographic evidence of bone ingrowth into the bone-prosthesis interface was observed in all stems. There was no significant difference in the distance from the tip of the curved stem to the body midline and the apex of the acetabulum at immediate postoperatively and last follow-up compared with the distance from the center of the femoral head to the body midline and the apex of the acetabulum before operation, respectively (P>0.05), and there was no significant difference in the above indexes between immediate postoperatively and last follow-up (P>0.05). The differences in the neck-shaft angle at various time points before and after operation were also not significant (P>0.05). At last follow-up, the MSTS score was 26.1±1.2 and the VAS score was 0.1±0.5, which were significantly improved when compared with those before operation [19.4±2.1 and 5.7±1.0, respectively] (t=14.735, P<0.001; t=21.301, P<0.001). At last follow-up, none of the patients walked with the aid of crutches or other walkers. CONCLUSION The 3D printed customized cementless intercalary endoprosthesis with an intra-neck curved stem is an effective method for reconstructing ultrashort bone segments in the proximal femur following malignant tumor resection. The operation is reliable, the postoperative lower limb function is satisfactory, and the incidence of complications is low.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Femur/surgery* ; Lower Extremity ; Bone-Implant Interface ; Femur Head ; Artificial Limbs

OBJECTIVE: To investigate the effectiveness of three-dimensional (3D)-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic prosthesis. METHODS: Between February 2017 and January 2020, 11 patients with aseptic loosening or screw fracture of modular hemi-pelvic prosthesis were revised using 3D-printed hemi-pelvic prostheses. There were 7 males and 4 females with an average age of 44 years (range, 25-60 years). In the first operation, all patients underwent total tumor resection, modular hemi-pelvic prosthesis reconstruction, and autologous femoral head transplantation. According to the Enneking pelvic partition system, 8 cases were resected in zones Ⅰ+Ⅱ and 3 cases in zones Ⅰ+Ⅱ+Ⅲ. The interval from the initial operation to this revision ranged from 14.3-66.2 months, with an average of 35.8 months. The operation time, the amount of intraoperative bleeding, and the occurrence of complications were recorded. At 6 months after the first operation, before revision, and at last follow-up, the American Musculoskeletal Tumor Society (MSTS) score and Harris score were used to evaluate the recovery of lower limb function. The pain-free walking distance of patients without brace assistance was recorded at last follow-up. X-ray films were taken at 1 month after the first operation, before revision, and at 1 month after revision, the acetabulum position was assessed by the differences in weight arm and cup height between bilateral hip joints. At last follow-up, the digital X-ray tomography was taken to evaluate the prosthesis-bone integration and the occurrence of aseptic loosening. RESULTS: The operation time was 182.6-238.0 minutes (mean, 197.4 minutes). The amount of intraoperative bleeding was 400-860 mL (mean, 550.0 mL). All incisions healed by first intention with no infection, hip dislocation, nerve damage, or vascular-related adverse events. The MSTS score and Harris score at last follow-up were significantly higher than those at 6 months after the first operation and before revision ( P<0.05), while the score before revision was significantly lower than that at 6 months after the first operation ( P<0.05). At last follow-up, the patients were able to walk more than 1 000 meters painlessly without brace assistance. Imaging review showed that the difference of cup height at 1 month after revision was significantly lower than that at 1 month after the first operation and before revision, and at 1 month after the first operation than before revision operation, and the differences were significant ( P<0.05). There was no significant difference in the difference of weight arm among three time points ( P>0.05). All prostheses were well integrated, and no aseptic loosening of the prosthesis or screw fracture occurred. CONCLUSION Revision with 3D-printed hemi-pelvic prostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening or screw fracture of modular hemi-pelvic prosthesis. Early postoperative rehabilitation training can maximize the recovery of patient limb function, reduce pain during walking, and reduce the incidence of complications.
Male ; Female ; Humans ; Adult ; Arthroplasty, Replacement, Hip/methods* ; Hip Prosthesis ; Treatment Outcome ; Prosthesis Failure ; Fractures, Bone/surgery* ; Retrospective Studies ; Neoplasms