Background Due to the prominent particularity of medical work,nurses are prone to developing depression,which not only poses a considerable threat to the physical and mental health of nurses,but also affects the quality of nursing to some extent.Occupational stress is a known contributor to depression in nurses,whereas relatively little research has been done to investigate the underlying mediation path.Objective To explore the mediation effect of perceived organizational support and psychological capital on the relationship between occupational stress and depression among nurses,and to provide theoretical references for the prevention and treatment of occupational stress-induced depression in nurses.Methods From March to August 2019,a stratified random sampling method was utilized to select a sample size of 720 nurses in each department of a grade A tertiary hospital in Shandong Province.All subjects were assessed using Effort-Reward Imbalance Questionnaire(ERI),Perceived Organization Support Questionnaire(POS),Psychological Capital Questionnaire(PCQ)and Center for Epidemiologic Studies Depression Scale(CES-D).Pearson correlation was adopted to examine the correlation among above scales,and multilevel mediation analyses were conducted with model 6 in Process macro(version 3.3)for SPSS 26.0 using Bootstrap re-sampling method.Results A total of 658 nurses(91.39%)completed the effective questionnaire survey.ERI score was positively correlated with CES-D score(r=0.499,P<0.01),and negatively correlated with POS and PCQ scores(r=-0.318,-0.275,P<0.01).POS score was positively correlated with PCQ score(r=0.455,P<0.01),and negatively correlated with CES-D score(r=-0.401,P<0.01).PCQ score was negatively correlated with CES-D score(r=-0.567,P<0.01).The total effect value of occupational stress on depression was 0.466(95%CI:0.399～0.534).Perceived organizational support(indirect effect value of 0.027,95%CI:0.006～0.057)and psychological capital(indirect effect value of 0.059,95%CI:0.013～0.120),separately from each other,mediated the relationship between occupational stress and depression,and a chained mediation effect of perceived organizational support and psychological capital was also demonstrated(indirect effect value of 0.051,95%CI:0.031～0.082),accounting for 10.94%of the total effect.Conclusion Occupational stress is a influencing factor of nurses' depression,which can affect the occurrence of depression both directly and indirectly through either separate or chained mediation of perceived organizational support and psychological capital.

Objective:To investigate the expression of programmed cell death ligand 1 (PD-L1), clinicopathologic features, immunohistochemical expression and molecular characteristics in fumarate hydratase (FH)-deficient renal cell carcinoma and to explore the potential application of immunotherapy in the patients.Methods:There were six patients with FH-deficient renal cell carcinoma treated at the First Affiliated Hospital of Fujian Medical University between January 2020 and October 2022. The clinical data, histological morphology, immunophenotype, PD-L1 expression and next-generation sequencing results were tabulated and analyzed.Results:There were 6 patients, all male, age ranged from 37 to 72 years (mean 45.7 years). Four cases were high-grade (WHO/ISUP grade3-4) with 2 or more histologic patterns, including papillary (most common), glandular, tubular, vesicular, ethmoid, nest-like, cystic and solid structures. Two cases were low-grade which showed nest-like, glandular, or tubular arrangement with eosinophilic flocculent cytoplasm and small intracellular vacuoles. Immunohistochemical analysis revealed strong expression of 2SC in all 6 cases, negative expression of FH in 5 cases, and positive expression of GATA3 in 5 cases. In high-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes in advanced tumor invasion were 180.3/mm 2 and 130.5/mm 2, respectively. PD-L1 combined positive scores (CPS) were 20, 50, 5 and 30, respectively. The Ki-67 proliferative index were 20%, 20%, 10% and 30%, respectively. In low-grade cases, the mean values of CD4 and CD8 positive T-lymphocytes were 123.0/mm 2 and 100.5/mm 2, respectively. The PD-L1 CPS score was 1, and the Ki-67 proliferation index was 3%. High-throughput sequencing showed FH gene somatic mutation in 3 cases, FH gene germline mutation in 2 cases, and FH gene mutation was not detected in one case. Conclusion:FH-deficient renal cell carcinoma is more commonly high-grade than low grade. FH and 2SC are immunohistochemical markers used in the diagnosis of FH-deficient renal cell carcinoma, and GATA3 positivity is supportive of the diagnosis. The tumor infiltration of high-grade FH-deficient renal cell carcinoma shows an increase in CD4 and CD8 positive T-lymphocytes, and high expression of PD-L1; thus, anti-PD-L1 immunotherapy can be used as a treatment option.

Objective:To investigate the effectiveness of the S-PAL model (combining a student standardized patient with peer assisted learning) in experimental teaching of physical diagnostics.Methods:Eighty-four undergraduate students of grade 2022 in clinical medicine of Chongqing Medical University were divided into experimental group ( n=44, experimental class teaching combined with S-PAL model-based autonomous practice) and control group ( n=40, experimental class teaching combined with traditional autonomous practice). Performance evaluation and teaching feedback and satisfaction survey were conducted. SPSS 27.0 was used to perform the t-test, chi-square test, and Fisher's exact test. Results:There were no significant differences between the two groups in terms of age, sex, the grade point average, and pre-training theoretical scores. The academic assessment score of the experimental group (66.34±15.45) was significantly higher than that of the control group (55.12±15.02). The experimental group was superior to the control group in clinical skills assessed with the mini-clinical evaluation exercise. The experimental group had a higher degree of satisfaction with teaching than the control group. The experimental group highly accepted autonomous practice based on the S-PAL model.Conclusions:The S-PAL model can improve medical undergraduates' academic performance and satisfaction with teaching in physical diagnostics, and also promote their doctor-patient communication skills, which is a good self-learning model as a complement to physical diagnostics teaching.

Atherosclerosis is a lipid-driven chronic inflammatory disease that typically forms plaques in large and medium-sized arteries and is a major cause of ischemic heart disease and stroke.Recent studies have found that during the progression of atherosclerosis,the level of cellular glycolysis in plaques increases,leading to excessive production and excretion of lactate and acidification of the extracellular environment,which may further affect the development of athero-sclerosis through multiple mechanisms.This article reviews the research progress on the role of lactate metabolism in ath-erosclerosis,which may provide new therapeutic targets and directions for the prevention and treatment of atherosclerosis.

Objective:To analyze the risk factors and pathogen distribution of ventilator-associated pneumonia (VAP) in patients with acute respiratory distress syndrome (ARDS).Methods:A retrospective analysis was conducted on the clinical data of 118 patients with ARDS who received treatment at Xi'an International Medical Center Hospital from January 2020 to January 2023. The patients were divided into two groups: the VAP group ( n = 38) and the non-VAP group ( n = 80), based on the presence of concurrent VAP. Serological indicators, blood gas analysis parameters, and ventilator settings were compared between the two groups to identify the risk factors associated with the occurrence of VAP. Pathogenic bacteria in the patients' sputum were also detected. Results:Among the 118 patients, there were 79 males and 39 females, with an average age of (53.1 ± 9.6) years. The primary underlying conditions leading to ARDS included chronic obstructive pulmonary disease in 49 cases (41.53%), sepsis in 20 cases (16.95%), severe pneumonia in 17 cases (14.41%), and extensive stroke in 16 cases (13.56%). Univariate analysis revealed that, compared with the non-VAP group, the VAP group had significantly more severe ARDS ( Z = -4.73, P < 0.05). Compared with the non-VAP group, the levels of albumin, platelets, and procalcitonin in the VAP group were significantly lower ( t = 13.75, 3.11, 2.27, all P < 0.05), while levels of high-sensitivity C-reactive protein, transforming growth factor beta (TGF-β), and angiotensin Ⅱin the VAP group were significantly higher ( t = 2.51, 26.63, 27.50, all P < 0.05). The VAP group had a significantly higher proportion of patients who experienced coma, underwent tracheostomy, and received more than two types of antibiotics (χ2 = 14.84, 19.04, 11.22, all P < 0.05). The VAP group also had significantly longer duration of antibiotic use compared with the non-VAP group ( t = 6.88, P < 0.05). Multivariate analysis showed that albumin ( OR = 2.632, 95% CI: 1.398-3.749), high-sensitivity C-reactive protein ( OR = 2.358, 95% CI: 1.534-4.036), coma ( OR = 3.035, 95% CI: 2.034-3.834), and use of more than two types of antibiotics ( OR = 2.005, 95% CI: 1.363-2.846) were independent risk factors for the occurrence of VAP in patients with ARDS (all P < 0.05). In 38 patients with VAP, 63 pathogenic strains were isolated from sputum, while in 80 patients with non-VAP, 128 pathogenic strains were isolated. The most common pathogens identified were Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus. In the VAP group, a single pathogen was identified in 16 cases (42.11%), whereas in the non-VAP group, a single pathogen was identified in 51 cases (63.75%). Two types of pathogens were found in 14 cases (36.84%) of the VAP group and 25 cases (31.25%) of the non-VAP group, while three or more pathogens were detected in 8 cases (21.05%) of the VAP group and 4 cases (5.00%) of the non-VAP group. The survival rates for the VAP and non-VAP groups were 57.9% (22/38) and 85.0% (68/80), respectively, with the non-VAP group showing a significantly higher survival rate (χ2 = 22.67, P < 0.001). Conclusion:The risk of VAP in patients with ARDS is high, with two or more pathogen infections being predominant. Clinical interventions should be strengthened.

ObjectiveTo observe the effect of video-based mirror therapy on lower limb motor function, walking ability, and balance of stroke patients at recovery stage. MethodsFrom January to October, 2022, 43 stroke patients in Beijing Bo'ai Hospital were randomly divided into control group (n = 22) and mirror therapy group (n = 21). Both groups received routine rehabilitation, and the mirror therapy group received video-based mirror therapy additionally, for four weeks. They were assessed with Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Functional Ambulation Category (FAC) and Berg Balance Scale (BBS) before and after treatment. ResultsAfter treatment, the scores of FMA-LE, FAC and BBS improved significantly in both groups (|t| > 6.205, P < 0.001), and the scores of FMA-LE and BBS were better in the mirror therapy group than in the control group (|t| > 2.164, P < 0.05). ConclusionCombining with video-based mirror therapy could facilitate to improve the lower limb motor function and balance ability of stroke patients at recovery stage.

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.

Exosomes are small vesicles with nanoscale lipid bilayer structures, which are secreted by various cells and are widely present in biological fluids, with complex contents and multiple biological functions.Exosomes play an important role in the development of glaucoma.Exosomes in the eye are involved in trabecular meshwork cell regulation by transporting glaucoma-associated proteins, regulating the Wnt signaling pathway, and affecting extracellular matrix turnover, thereby affecting the atrial circulation.Microglial exosomes mediate retinal neuroinflammation and related inflammatory signaling pathways.In addition, the stable presence of exosomes in intraocular fluid, in which differentially expressed proteins, RNA and other contents give exosomes potential as glaucoma biomarkers.In the treatment of glaucoma, stem cell-derived exosomes inhibit glial cell activation and neuroinflammation, reduce the loss of retinal ganglion cells, and act as neuroprotective agents.Exosomes can cross the blood-retinal barrier, deliver neurotrophic factors, drugs or other therapeutic molecules to target cells, regulate the function of target cells, and provide a new therapeutic tool for glaucomatous optic nerve degeneration.This paper summarized the research progress in the field of glaucoma and exosomes at home and abroad, and reviewed the role of exosomes and related mechanisms in the development, diagnosis, and treatment of glaucoma, expecting to provide new ideas for the early diagnosis and treatment of glaucoma.

ObjectiveTo explore the effects of different intensity of wearable lower limb rehabilitation robot-assisted training on walking function, lower limb motor function, balance function and functional independence of stroke patients. MethodsFrom November, 2021 to December, 2022, 60 stroke patients hospitalized in Beijing Bo'ai Hospital were randomly divided into control group (n = 20), observation group 1 (n = 20) and observation group 2 (n = 20). All the groups received routine rehabilitation, while the control group received routine walking training 30 minutes a day, the observation group 1 received wearable lower limb rehabilitation robot-assisted training 30 minutes a day, and the observation group 2 received wearable lower limb rehabilitation robot-assisted training 60 minutes a day, for four weeks. They were assessed with Functional Ambulation Category scale (FAC), Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Berg Balance Scale (BBS) and Rivermead Mobility Index (RMI) before and after treatment. ResultsOne case in the observation group 1 and three cases in the observation group 2 dropped down. The FAC, FMA-LE, BBS and RMI scores improved in all the three groups after treatment (|Z| > 3.448, |t| > 8.102, P < 0.001), and there was no significant difference in all the indexes among the three groups (|H| < 4.643, F = 1.454, P > 0.05); however, the improvement of BBS score was more in the observation group 1 than in the control group (P < 0.05), and the improvement of all the indexes was more in the observation group 2 than in the control group (P < 0.05). ConclusionThe wearable lower limb rehabilitation robot-assisted training may promote the recovery of walking function, lower limb motor function, balance function and functional independence of stroke patients, and high-intensity training seems to be more effective.

AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P<0.05). There was no statistical significance in the comparison of alpha-fetoprotein and child-pugh grade between the two groups after treatment (P>0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.