Objective To investigate the role and potential mechanisms of tumor necrosis factor alpha-inducible protein 8-like molecule 1(TNFAIP8L1)in acute liver injury in mice.Methods The second generation of C57BL/6J male wild-type(WT)mice and the C57BL/6J female TNFAIP8L1+/-mice and WT mice were selected to further self-breed the third generation of male TNFAIP8L1-/-mice and the third generation of WT male mice.Five normal third-generation male WT mice and five normal third-generation male TNFAIP8L1-/-mice were selected.The serum alanine aminotransferase(ALT)levels of the two types of normal mice were measured and compared.The infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of normal mice were observed after hematoxylin & eosin(HE)staining.Flow cytometry was used to detect the percentages of neutrophils(Neu),eosinophils(EOS),dendritic cells(DC),bone marrow-derived macrophages(BMDMs),and bone marrow-derived mononuclear cell(BMNCs)in the liver myeloid cell subsets of the two types of normal mice.Another 5 third-generation male WT mice and 4 third-generation male TNFAIP8L1-/-mice were selected to induce acute liver injury mouse models using lipopolysaccharide(LPS)/D-galactosamine(D-Gal).After 24 hours,the serum ALT levels of the two types of acute liver injury mice were detected and compared,the infiltration of inflammatory cells and cell necrosis in the liver tissues of the two types of acute liver injury mice were observed,and the percentages of Neu,EOS,DC,BMDMs and BMNCs in the liver myeloid cell subsets of the two types of acute liver injury mice were measured by using the above methods.Results There was no significant difference in the percentages of Neu,EOS,DC,BMDMs and BMNCs,and serum ALT levels in the livermyeloid cell subsets of normal WT mice and TNFAIP8L1-/-mice(P＞0.05).HE staining results of liver tissues in normal WT mice and TNFAIP8L1/mice showed that hepatic lobules were structurally complete and clear,hepatocytes were morphologically normal and arranged neatly,and there was no obvious inflammatory cell infiltration or cell necrosis.Twenty-four hours after acute liver injury,the percentages of Neu and BMNCs in the liver myeloid cell subsets and the serum ALT levels in the liver tissues of TNFAIP8L1-/-mice were significantly higher than those of WT mice(P＜0.05);there was no significant difference in the percentages of EOS,DC and BMDMs in the liver myeloid cell subsets of mice between the two groups(P＞0.05).In the liver tissues of WT mice with acute liver injury,hepatic lobules were structurally blurred,hepatocytes were swollen with scattered vacuolated steatosis,and a small amount of inflammatory cells were infiltrated.In the liver tissues of TNFAIP8L1/mice with acute liver injury,hepatic lobules were structurally non-existent,and hepatocytes were severely damaged and extensively necrotic,with a large amount of inflammatory cell infiltration.Conclusion The deficiency of the TNFAIP8L1 gene in mice does not affect the development of liver myeloid cells and the homeostasis of the liver.TNFAIP8L1 plays an inhibitory role in the occurrence and development of acute liver injury.TNFAIP8L1 gene deficiency aggravates LPS/D-Gal-induced acute liver injury,possibly by increasing Neu and BMNCs infiltration and recruiting other types of immune cells to infiltrate liver tissues,thereby exacerbating liver cell necrosis.

Objective:To understand the real feelings of oncology nurses in using arm port, so as to provide basis for taking targeted intervention measures to reduce the problems in the process of nurses using arm port and continuously improve the quality of intravenous therapy.Methods:Using the purposive sampling method, a total of 13 nurses from Oncology Department of Beijing Hospital were selected for in-depth interviews from October to November 2023, and the data were analyzed using Colaizzi's 7-step analysis method.Results:Three themes were extracted, including positive experiences (high sense of security and benefit), growth and reflection and negative experiences (concerns about unknown risks, tension and stress) .Conclusions:As a relatively safe route of administration, arm port is worthy of further promotion and application. There are many concerns among oncology nurses during the use of arm port. It is recommended that medical staff jointly strengthen comprehensive evaluations of patients and managers provide corresponding training and guidance for weak links to alleviate nurses' concerns during the use of arm port, in order to provide patients with higher quality intravenous treatment nursing services.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To construct a discharge preparation service program for elderly lung cancer patients and their caregivers based on binary coping theory, evaluate its clinical feasibility.Methods:To develop discharge preparation service for elderly lung cancer patients and their caregivers by literature retrieval, expert correspondence consultation and theoretical research. The program included three themes: binary evaluation, binary management behaviorand binary health, and six intervention strategies: evaluation of symptoms, care goals and intentions, decision making, emotional communication support, management of physical function changes and general health behavior. From July to September 2021, 30 pairs of elderly lung cancer patients and their caregivers were recruited and assigned into the control group and the experimental group with 15 pairs in each group according to random numbers generated by computer. The feasibility and clinical effect of the program were evaluated by feasibility evaluation index, discharge readiness, dual coping and comprehensive needs scale of caregivers.Results:In this study, the recruitment rate was 76%(32/42), the retention rate was 94%(30/32), and the acceptance rate of the intervention plan in the experimental group was 100%. After intervention, the total scores of discharge readiness was (83.00 ± 2.59), the patient dyadic coping was (136.80 ± 4.54), caregiver dyadic coping was (136.33 ± 3.56) and caregiver comprehensive needs was (124.37 ± 11.69) in the experimental group, which were better than those of in the control group, (74.40 ± 4.17), (129.07 ± 4.83), (120.33 ± 9.17) and (206.57 ± 9.14), the differences were statistically significant ( t values were -6.78- 5.54, all P< 0.05). Conclusion:The discharge preparation service plan for elderly lung cancer patients and caregivers based on dyadic coping theory is scientific and feasible, but the plan still needs further optimization, improvement and large sample randomized controlled trial to verify.

Objective:To study the key factors that affect patients′ perception among the five dimensional factors of patients′ perceived service quality, and explore how to effectively rebuild patients′ confidence in the process of handling services with quality defects.Methods:A total of 388 12345 work orders from a Beijing stomatological hospital in 2021 were collected. The problems and solutions of patients′feedback were classified and standardized into tangibility, reliability, responsiveness, assurance and empathy. Chi-square test and logistic regression were used to analyze the relationship between relevant factors and problem solving rate, patient satisfaction.Results:There were 513 feedback questions in 388 return visit work orders, with 1.32 items for each. There were 83, 112, 126, 111 and 81 questions in the five dimensions of tangibility, reliability, responsiveness, assurance and empathy; 273 work orders had single-dimension problems, accounting for 70.4%, 105 work orders had two dimensional problems, and 10 work orders had three dimensional problems. Among them, the assurance dimension problem accounts for 47% and 100% of the work orders of two-dimension and three-dimension problems respectively; The proportion of unsolved responsiveness dimension problems was the highest, accounting for 31.7%, and there was a negative correlation between responsiveness dimension problems and patient satisfaction rate( r=-0.709). Conclusions:In the process of medical service, the basic quality and skills of medical staff are the basis of building patient trust. In the process of handling medical services with quality defects, it is most important that quickly respond to patients′ queries, which could help to rebuild patients′ confidence in the quality of services.

Objective:To investigate the microstructural abnormalities of the white matter in first-episode medication-free patients with schizophrenia (FESZ) based on inter-voxel diffusivity metric local diffusion homogeneity (LDH) and traditional intra-voxel diffusivity metric.Methods:A total of 56 FESZ patients admitted to our hospital from January 2020 to December 2021 were selected as research subjects, and 64 healthy volunteers recruited during the same period were selected as healthy controls. All subjects accepted magnetic resonance diffusion tensor imaging, and the LDH, anisotropy fraction (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were obtained by FSL and PANDA software. Tract-based spatial statistics (TBSS) method was employed to analyze and compare the differences in the diffusivity metrics of white matter fibers between the two groups. For white matter fiber tracts with significant inter-group differences, receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of each diffusivity metric in FESZ, and Spearman partial correlation was used to analyze the relation between each diffusivity metric and positive and negative symptom scale (PANSS) scores.Results:As compared with that in the heathy control group, LDH in partial voxel clusters in bilateral anterior thalamic radiation of the FESZ group was statistically increased ( P<0.05, FWE correction). As compared with that in the heathy control group, the mean LDH in the tracts of interest (TOI) of the right inferior longitudinal fasciculus and the right uncinate fasciculus in the FESZ group was significantly increased ( P<0.05, FDR correction). In the above 4 fasciculi, ROC analysis showed that LDH had diagnostic efficacy ( P<0.05), and the diagnostic efficacy of LDH was the highest when the fasciculi structures were combined (AUC=0.733, P<0.001). LDH in white matter fiber tracts with significant inter-group differences had no statistical correlation with PANSS scores ( P>0.05). No voxel clusters or TOIs enjoyed statistical differences between groups were noted in the FA, MD, AD and RD parameter maps ( P>0.05). Conclusion:The inter-voxel diffusivity metric LDH can detect the compensatory changes of white matter microstructure in FESZ patients that could not be detected by traditional intra-voxel diffusivity metric.

Objective:To explore the application effect of defect scenario simulation combined with joint review action in the training of blood-borne occupational exposure of nursing assistants.Methods:From February 1, 2020 to February 1, 2021, a total of 97 nursing assistants from Central District of Provincial Hospital Affiliated to Shandong First Medical University, were selected as the experimental group and 89 nursing assistants from the Eastern District were selected as the control group. The control group received routine training, while the observation group received defect scenario simulation combined with action training. After 1 year of training, the incidence of blood-borne occupational exposure and blood-borne occupational exposure knowledge scores of nursing assistants in the two groups were compared.Results:During the intervention period, 1 nursing assistant in the experimental group resigned, 2 nursing assistants asked for leave twice or more, and 94 nursing assistants were finally enrolled. In the control group, 2 nursing assistants resigned and 3 nursing assistants asked for leave twice or more, and 84 nursing assistants were eventually enrolled. The incidence of blood-borne occupational exposure of nursing assistants in the experimental group was lower than that in the control group and the score of blood-borne occupational exposure knowledge was higher than that in the control group, and the differences were all statistically significant ( P<0.05) . Conclusions:Defect scenario simulation combined with joint review action has a good effect in blood-borne occupational exposure training of nursing assistants, which can reduce the incidence of blood-borne occupational exposure and improve their blood-borne occupational exposure knowledge scores. It is worthy of clinical promotion.

Objective:To investigate the clinical and pathological features and prognosis of patients with microfocal prostate adenocarcinoma.Methods:Clinical and pathological data of the patients diagnosed with microfocal adenocarcinoma on prostate biopsy at the West China Hospital from 2013 to 2019 were collected. Microfocal adenocarcinoma was defined as follows: Gleason score of 3+3=6, total number of the cores ≥10, number of the positive cores ≤2, and proportion of the tumor in each positive core<50%. Clinicopathological parameters, treatment plans and follow-up data were collected. Pathological information of the biopsy and radical resection specimens was used to analyze the correlation between pathological parameters in the biopsy report and adverse pathological features of radical resection specimens, including increased Gleason score, capsule invasion, positive surgical margin and perineural invasion.Results:A total of 206 cases of microfocal adenocarcinoma were diagnosed on prostate biopsies from 2013 to 2019, accounting for 6.7% of all adenocarcinoma cases. There were 139 cases of 1 positive core and 67 cases of 2 positive cores. Patients with microfocal adenocarcinoma were younger than those with non-microfocal adenocarcinoma (69 years versus 71 years, P<0.001). Compared with patients with non-microfocal adenocarcinoma, the pre-biopsy total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) levels in patients with microfocal adenocarcinoma were both lower (11.2 μg/L 2 versus 23.7 μg/L 2; 1.4 μg/L 2 versus 3.0 μg/L 2, P<0.001), the fPSA/tPSA level was higher (12.9% versus 10.7%, P<0.05), the prostate volume was larger (38.9 mL versus 34.3 mL, P<0.05), and the PSA density was lower (0.3 μg/L 2 versus 0.8 μg/L 2, P<0.001). 130 patients underwent radical prostatectomy, 30 patients chose active monitoring, 31 patients chose endocrine or radiation therapy, and 15 patients were lost to follow-up. Three patients in the active surveillance group underwent radical prostatectomy for disease progression after 21-39 months observation. Biochemical relapses occurred in two patients in the radical prostatectomy group. The remaining patients have no disease progression or recurrence at present. Compared with radical prostatectomy specimens, Gleason score in the biopsy material was increased in 64/115 patients (55.7%). Among resection excision specimens, 14 cases (12.2%) had extraprostatic extension (EPE), 35 cases (30.4%) had perineural invasion, and 16 cases (13.9%) had a positive margin. Univariate and multivariate analyses showed that low fPSA/tPSA ratio and 2 positive cores were independent risk factors for Gleason score increase in the radical prostatectomy specimens. A low fPSA/tPSA ratio was an independent risk factor for perineural invasion. Low fPSA/tPSA ratio and low prostate volume were associated with a positive margin in radical prostatectomy specimens. Conclusions:In this study, patients diagnosed with microfocal adenocarcinoma on prostate biopsy account for a high proportion of the patients with increased Gleason score in the radical prostatectomy specimens, and there is a certain proportion of adverse pathological features in the radical specimens. Therefore, for the patients with only a small amount of low-grade adenocarcinoma found in biopsy, PSA levels and PSA density should be taken into consideration in treatment selection.

In order to overcome the shortcomings of high false positive rate and poor generalization in the detection of microcalcification clusters regions, this paper proposes a method combining discriminative deep belief networks (DDBNs) to automatically and quickly locate the regions of microcalcification clusters in mammograms. Firstly, the breast region was extracted and enhanced, and the enhanced breast region was segmented to overlapped sub-blocks. Then the sub-block was subjected to wavelet filtering. After that, DDBNs model for breast sub-block feature extraction and classification was constructed, and the pre-trained DDBNs was converted to deep neural networks (DNN) using a softmax classifier, and the network is fine-tuned by back propagation. Finally, the undetected mammogram was inputted to complete the location of suspicious lesions. By experimentally verifying 105 mammograms with microcalcifications from the Digital Database for Screening Mammography (DDSM), the method obtained a true positive rate of 99.45% and a false positive rate of 1.89%, and it only took about 16 s to detect a 2 888 × 4 680 image. The experimental results showed that the algorithm of this paper effectively reduced the false positive rate while ensuring a high positive rate. The detection of calcification clusters was highly consistent with expert marks, which provides a new research idea for the automatic detection of microcalcification clusters area in mammograms.
Algorithms ; Breast Neoplasms/diagnostic imaging* ; Calcinosis/diagnostic imaging* ; Early Detection of Cancer ; Humans ; Mammography ; Neural Networks, Computer

Blocking the programmed death-ligand 1 (PD-L1) on tumor cells with monoclonal antibody therapy has emerged as powerful weapon in cancer immunotherapy. However, only a minority of patients presented immune responses in clinical trials. To develop an alternative treatment method based on immune checkpoint blockade, we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells specifically knocking out Cyclin-dependent kinase 5 () gene . The expression of PD-L1 on tumor cells was significantly attenuated by knocking out , leading to effective tumor growth inhibition in murine melanoma and lung metastasis suppression in triple-negative breast cancer. Importantly, we demonstrated that aPBAE/Cas9-Cdk5 treatment elicited strong T cell-mediated immune responses in tumor microenvironment that the population of CD8 T cells was significantly increased while regulatory T cells (Tregs) was decreased. It may be the first case to exhibit direct PD-L1 downregulation CRISPR-Cas9 genome editing technology for cancer therapy. It will provide promising strategy for preclinical antitumor treatment through the combination of nanotechnology and genome engineering.