The epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation is a rare subtype of mutations in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC carrying the EGFR ex20ins mutation tend to have poor responses to traditional EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and immunotherapy, leading to a poor clinical prognosis. Significant progress has been made in the development of new drugs targeting the EGFR ex20ins mutation. The research on new drugs targeting EGFR ex20ins mutations has made significant progress. The main ones include new EGFR-TKIs (such as sunvozertinib, mobocertinib, and furmetinib, etc.), bispecific antibodies (such as amivantamab, JMT101, and GB263T, etc.), and emerging drugs such as AUY922. These agents have demonstrated promising efficacy in clinical trials, improving the objective response rate and progression-free survival of patients, and are expected to improve overall survival. An in-depth analysis of the mechanism of action and clinical trial progress of these novel targeted drugs for EGFR ex20ins-mutated NSCLC can offer new therapeutic strategies for patients with EGFR ex20ins-mutated NSCLC.

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 develop a military identity scale and to evaluate its reliability and validity.Methods The theoretical and structural models of the scale were determined based on literature review and interviews.An item pool was established,test items were compiled,and the basic items were formed after revision by experts.Several servicemen were selected.Sample 1 was used for item analysis and exploratory factor analysis,and sample 2 was used for confirmatory factor analysis and internal consistency test.The reliability of the scale was tested by Cronbach's α coefficient and split-half reliability.The construct validity was tested by correlation analysis and confirmatory factor analysis.The military job burnout scale was used as criteria to test the criterion validity.Results The scale finally included 23 items in 4 factors(cognition,affection,sense of adaptation,and efficacy),which explained 54.087%of the total variance.The Cronbach's α coefficient of the scale was 0.925,and the Cronbach's α coefficients of the 4 factors were 0.843,0.899,0.854,and 0.835,respectively.The split-half reliability of the scale was 0.873,and the split-half reliability of the 4 factors was 0.812,0.882,0.870,and 0.821,respectively.The scale had good construct validity(the goodness of fitting χ2/df was 1.978,the comparative fit index was 0.927,the growth fitting index was 0.928,the Tucker-Lewis index was 0.916,the root mean square error of approximation was 0.055,and the goodness of fit index was 0.896).Conclusion The military identity scale developed in this study has good validity and reliability,and can be used to evaluate the identity of servicemen in China.

Root position plays an important role in healthy, stable, and aesthetic orthodontic treatment. In the past, two-dimensional radiographic images were used to assess the accuracy and precision of tooth root positions. In recent years, the use of cone beam CT (CBCT) and its reconstructed images to measure the three-dimensional spatial position and angle of root position has become mainstream. The root position is mainly described by measuring the relationship between the root and adjacent structures in the buccolingual, vertical, and mesiodistal directions as well as the root angle. The thickness of the alveolar bone on the buccolingual side of the root represents the buccolingual position, the vertical height in the alveolar bone and the relationship between apex and maxillary sinus represents the vertical position, the interroot alveolar bone thickness represents the mesiodistal position of the root, and the root angle is mostly based on incisal mandibular plane angle, angulation, torque, and other angles in the traditional two-dimensional measurement. Fitting CBCT and digital model data can be used to monitor the relationship between root and alveolar bone during orthodontic treatment, but a more comprehensive, standardized three-dimensional tooth root position measurement method is required to make full use of the root data provided by CBCT to study the relative optimal position of the tooth root at different anatomical levels, which combines with computer technology to optimize the digital design of orthodontic diagnosis and treatment.

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.
Anilides/pharmacology* ; Cerebral Hemorrhage/drug therapy* ; Hematoma/drug therapy* ; Humans ; Macrophages ; Microglia ; Neuroprotection ; PPAR gamma ; Retinoid X Receptor alpha

0bjective To explore the effects of narrative nursing on posttraumatic growth for patients with amputation. Methods From December 2016 to March 2018,a total of 62 hospitalized patients with amputation were randomly assigned into the control group and the intervention group by random number table.The control group received routine nursing,the intervention group received narrative nursing on the basis of control group.Two groups were evaluated by Posttraumatic Growth Inventory(PTGI) before and after intervention. Results Before intervention,the scores of reflections on life, personal strengths, new possibilities, relating to others, self-transformation and posttraumatic growth in the the control group were (19.87 ± 5.22), (7.90 ± 2.53), (8.83 ± 3.62), (9.73 ± 3.13), (10.63 ± 3.01), (56.97 ± 17.21) points, respectively. After intervention,the scores were (20.80±5.89), (8.80±2.17), (8.90±3.39), (10.27± 2.75), (11.07 ± 3.12), (59.83 ± 16.91) points, respectively, except new possibilities, the scores of each dimension and total scores of posttraumatic growth in the the control group were higher than before,the differences were statistically significant(t=3.00- 5.34, P＜0.05).Before intervention,the scores of reflections on life, personal strengths, new possibilities, relating to others, self-transformation and posttraumatic growth in the the intervention group were (20.28±4.94), (8.17±2.58), (8.59±3.48), (9.55± 2.90), (11.07±2.83), (57.66±16.42) points, respectively. After intervention, the scores were (23.79±4.70), (10.10±2.17), (10.72±3.34), (11.69±2.22), (12.79±3.28),(69.10±14.92) points, respectively, the scores of each dimension and total scores of posttraumatic growth in the intervention group were statistically higher than those in the control group and before intervention,the differences were statistically significant (t=10.61-16.75, P＜0.05). Conclusion Narrative nursing can effectively improve the level of posttraumatic growth and psychological state for patients with amputation.

Objective To investigate the level of occupational burnout and mindfulness among undergraduate nursing in-terns, and to analyze their relationship. Methods For convenient sampling, 600 nursing students who belong to 4 colleges and universities of Henan were investigated using the general information questionnaire, the Chinese version of Maslach Burnout Inventory (MBI) and Mindfulness Attention Awareness Scale (MAAS). Results The scores of occupational burnout were as follow: the score of emotional exhaustion was (33.46 ± 9.31) points, the score of depersonalization was (14.26 ± 5.91) points, the score of low personal achievement was (17.58 ± 8.49) points, the score of mindfulness was (57.27 ± 13.41) points. Mindfulness had a significant negative effect on job burnout, emotional exhaustion and low personal achievement. Level of mindfulness, language violence and work overtime in-terns, and possible of clinical nursing work in the future were the main factors influencing job burnout, and three factors could explain 25.4％ of job burnout. Conclusions Mindfulness had a significant negative effect on job burnout. Nursing educators and administrators should improve the level of mindfulness of nursing students to reduce their job burnout.

Objective To investigate the state of the aging perceptions and quality of life in the elderly patients with hypertension in Kaifeng city and their relationship. Methods A total of 156 elderly patients with hypertension in Kaifeng city were investigated by using a general data questionnaire, Chinese version of the Aging Perceptions and SF-36 quality of life assessment scale. Results The scores of the aging perceptions were higher than the median. The score of negative control was the highest with (3.72 ± 0.47) points, and the score of emotion representation was the lowest with (2.59±0.65) points. The scores of physical function, role limitation due to physical health, bodily pain, general health perception, emotional function and mental health of the elderly patients with hypertension were significantly lower than that of normal population (t=-17.074--3.492, P<0.01). Pearson correlation analysis showed that positive control, positive outcome, and recognition were significant positively correlated with quality of life (r=0.221- 0.352, P<0.05); acute/chronic time, emotional representation and negative result were significant negatively correlated with quality of life were presented (r=-0.478--0.310, P<0.01);periodic time was significant negatively correlated with mental health status (r=-0.314, P<0.01). Conclusions There is a significant correlation between the aging perceptions and quality of life in elderly hypertensive patients in Kaifeng city. The quality of life was significantly lower than that of normal population in China, and it was affected by the aging perceptions.

Objective To investigate the effect of Osthole on memory function of sleep deprivation(SD) mice. Methods Forty-eight male mice were randomly divided into 4 groups;normal control group(NC group ), large platform control group(TC group),sleep deprivation group(M group)and Osthole group(Ost group). The model of SD in mice was estabished by using improved multi platform method. The ability of learning and memory was tested by using Morris water maze test and pathological changes of hippocampal neurons in mice were observed by HE staining. The serum,hippcampus malondialdehyde(MDA)contents and superoxide dismutase(SOD)activity, so as the hippocampus No content,were detected. Results Compared with NC group and TC group,the escape la-tency of M group increased significiantly and the number of crossing platform decreased significantly. There were in-creased levels hippocampus tissue,serum MDA level,hippocampal SOD activity and NO content. After supplemen-tation of Osthole,the escape latency significantly shortened in mice. The number of crossing platform was increased while the contents of MDA both in hippocampus and serum were decreased,and the SOD activity in hippocampus re-turned to normal. However,the level of NO in hippocampus was not decreased. Conclusion Osthole can protect the memory function of SD mice by reducing the the damage of hippocampal neurons through antioxidant stress.