Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

Objective To explore the mechanism of Qingda Granules(QDG)for alleviating brain damage in spontaneously hypertensive rats(SHRs).Methods Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks.The control rats,along with 6 age-matched WKY rats,were treated with saline only.Blood pressure changes of the rats were monitored,and pathologies and neuronal apoptosis in the cerebral cortex were examined with HE staining and TUNEL staining.Cerebral cortical expressions of miR-124 and STAT3 mRNA were detected using RT-qPCR,and the protein expressions of NeuN,STAT3,Bcl-2,Bax,and cleaved caspase-3 were detected with immunohistochemistry and Western blotting.In a HT22 cell model of oxygen and glucose deprivation/reoxygenation(OGD/R),the effects of QDG on cell viability and apoptosis,expressions of miR-124 and STAT3 mRNA,and protein expressions of STAT3,Bcl-2,Bax,and cleaved caspase-3 were evaluated using CCK8 assay,Hoechst 33342 staining,RT-qPCR,and Western blotting.Results Compared with WKY rats,SHRs had significantly elevated systolic blood pressure,diastolic blood pressure and mean arterial pressure with significantly increased neuronal apoptosis in the cerebral cortex,reduced expressions of NeuN,miR-124 and Bcl-2,and enhanced expressions of STAT3,Bax and cleaved caspase-3(P＜0.05).All these changes in the SHRs were significantly ameliorated by treatment with QDG(P＜0.05).In the HT22 cell model,QDG treatment obviously reduced OGD/R-induced cell apoptosis,increased the expressions of miR-124 and Bcl-2,and suppressed the elevation of protein expressions of STAT3,Bax and cleaved caspase-3.Conclusion QDG inhibits cerebral cortical neuronal apoptosis and thereby attenuates brain damage in SHR rats by modulating the miR-124/STAT3 signaling axis.

Objective A rat model of cerebral small vessel disease(CSVD)was established by unilateral injection of a single dose of sodium laurate into the internal carotid artery.The effectiveness of the model was assessed by behavior scoring and analysis of serum-related indicators,cerebral infarction volume,cerebral microvascular density,hemodynamics,brain histopathology and the expression of blood-brain barrier(BBB)-related proteins.Methods SPF-grade male SD rats were divided randomly into a control group and a model group(n=6 per group).The model group received a single injection of 100 μL of sodium laurate(2 g/L)via the internal carotid artery,while the control group underwent the same surgical procedure but received an equal volume of saline.Neurobehavioral assessments were conducted using the Longa score and postural reflex test.Serum homocysteine(HCY)levels were measured by enzyme-linked immunosorbent assay.Cerebral infarction volume was detected by magnetic resonance imaging and changes in cerebral vascular density were observed by cerebrovascular imaging.The resistance index(RI)and perfusion index(PI)were measured by ultrasonography.Histopathological changes in brain tissue were evaluated by hematoxylin and eosin(HE)staining.Expression of the cerebral microvascular marker CD31 and tight junction proteins ZO-1 and Occludin in brain cortex tissue were detected by immunohistochemical staining.Results The Longa score,postural reflex score(P＜0.05),and cerebral infarction volume were significantly increased(P＜0.05)while the cerebral vascular density was decreased in the model group compared with the control group.Serum HCY levels,carotid RI,and PI values were all significantly increased in the model group(P＜0.05).HE staining revealed solidified neuronal nuclei and enlarged perivascular spaces in the brain cortex in the model group.Immunohistochemical staining revealed that CD31,ZO-1,and Occludin expression were significantly reduced in the brain cortex in the model group compared with the control group(P＜0.05).Conclusions A rat model of CSVD can be established rapidly and effectively by a single unilateral injection of high-concentration sodium laurate via the internal carotid artery.This model is characterized by neurobehavioral abnormalities,cerebral infarction,insufficient cerebral blood supply,reduced vascular density,and disruption of the BBB,suggesting that it may serve as an effective rat model for the study of CSVD.

Retinal artery occlusion(RAO)is a vascular neuro-ophthalmological emergency and a rare but serious complication of carotid artery stenting(CAS).It is characterized by a sudden decrease in vision or even vision loss in one eye.This article reports a case of central RAO caused by emboli through a branch of the external carotid artery during CAS,aiming to provide insights for optimizing CAS procedures,and preventing and controlling this complication.

In this study, we propose an automatic contour outlining method to measure the spatial resolution of homemade automatic tube current modulation (ATCM) phantom by outlining the edge contour of the phantom image, selecting the region of interest (ROI), and measuring the spatial resolution characteristics of computer tomography (CT) phantom image. Specifically, the method obtains a binarized image of the phantom outlined by an automated fast region convolutional neural network (AFRCNN) model, measures the edge spread function (ESF) of the CT phantom with different tube currents and layer thicknesses, and differentiates the ESF to obtain the line spread function (LSF). Finally, the values passing through the zeros are normalized by the Fourier transform to obtain the CT spatial resolution index (RI) for the automatic measurement of the modulation transfer function (MTF). In this study, this algorithm is compared with the algorithm that uses polymethylmethacrylate (PMMA) to measure the MTF of the phantom edges to verify the feasibility of this method, and the results show that the AFRCNN model not only improves the efficiency and accuracy of the phantom contour outlining, but also is able to obtain a more accurate spatial resolution value through automated segmentation. In summary, the algorithm proposed in this study is accurate in spatial resolution measurement of phantom images and has the potential to be widely used in real clinical CT images.
Phantoms, Imaging ; Tomography, X-Ray Computed/instrumentation* ; Algorithms ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods* ; Humans ; Polymethyl Methacrylate

OBJECTIVES: To explore the mechanism of Qingda Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs). METHODS: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks. The control rats, along with 6 age-matched WKY rats, were treated with saline only. Blood pressure changes of the rats were monitored, and pathologies and neuronal apoptosis in the cerebral cortex were examined with HE staining and TUNEL staining. Cerebral cortical expressions of miR-124 and STAT3 mRNA were detected using RT-qPCR, and the protein expressions of NeuN, STAT3, Bcl-2, Bax, and cleaved caspase-3 were detected with immunohistochemistry and Western blotting. In a HT22 cell model of oxygen and glucose deprivation/reoxygenation (OGD/R), the effects of QDG on cell viability and apoptosis, expressions of miR-124 and STAT3 mRNA, and protein expressions of STAT3, Bcl-2, Bax, and cleaved caspase-3 were evaluated using CCK8 assay, Hoechst 33342 staining, RT-qPCR, and Western blotting. RESULTS: Compared with WKY rats, SHRs had significantly elevated systolic blood pressure, diastolic blood pressure and mean arterial pressure with significantly increased neuronal apoptosis in the cerebral cortex, reduced expressions of NeuN, miR-124 and Bcl-2, and enhanced expressions of STAT3, Bax and cleaved caspase-3 (P<0.05). All these changes in the SHRs were significantly ameliorated by treatment with QDG (P<0.05). In the HT22 cell model, QDG treatment obviously reduced OGD/R-induced cell apoptosis, increased the expressions of miR-124 and Bcl-2, and suppressed the elevation of protein expressions of STAT3, Bax and cleaved caspase-3. CONCLUSIONS QDG inhibits cerebral cortical neuronal apoptosis and thereby attenuates brain damage in SHR rats by modulating the miR-124/STAT3 signaling axis.
Animals ; Rats, Inbred SHR ; MicroRNAs/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Apoptosis/drug effects* ; Rats, Inbred WKY ; Male ; Hypertension

Objective A rat model of cerebral small vessel disease(CSVD)was established by unilateral injection of a single dose of sodium laurate into the internal carotid artery.The effectiveness of the model was assessed by behavior scoring and analysis of serum-related indicators,cerebral infarction volume,cerebral microvascular density,hemodynamics,brain histopathology and the expression of blood-brain barrier(BBB)-related proteins.Methods SPF-grade male SD rats were divided randomly into a control group and a model group(n=6 per group).The model group received a single injection of 100 μL of sodium laurate(2 g/L)via the internal carotid artery,while the control group underwent the same surgical procedure but received an equal volume of saline.Neurobehavioral assessments were conducted using the Longa score and postural reflex test.Serum homocysteine(HCY)levels were measured by enzyme-linked immunosorbent assay.Cerebral infarction volume was detected by magnetic resonance imaging and changes in cerebral vascular density were observed by cerebrovascular imaging.The resistance index(RI)and perfusion index(PI)were measured by ultrasonography.Histopathological changes in brain tissue were evaluated by hematoxylin and eosin(HE)staining.Expression of the cerebral microvascular marker CD31 and tight junction proteins ZO-1 and Occludin in brain cortex tissue were detected by immunohistochemical staining.Results The Longa score,postural reflex score(P＜0.05),and cerebral infarction volume were significantly increased(P＜0.05)while the cerebral vascular density was decreased in the model group compared with the control group.Serum HCY levels,carotid RI,and PI values were all significantly increased in the model group(P＜0.05).HE staining revealed solidified neuronal nuclei and enlarged perivascular spaces in the brain cortex in the model group.Immunohistochemical staining revealed that CD31,ZO-1,and Occludin expression were significantly reduced in the brain cortex in the model group compared with the control group(P＜0.05).Conclusions A rat model of CSVD can be established rapidly and effectively by a single unilateral injection of high-concentration sodium laurate via the internal carotid artery.This model is characterized by neurobehavioral abnormalities,cerebral infarction,insufficient cerebral blood supply,reduced vascular density,and disruption of the BBB,suggesting that it may serve as an effective rat model for the study of CSVD.

Retinal artery occlusion(RAO)is a vascular neuro-ophthalmological emergency and a rare but serious complication of carotid artery stenting(CAS).It is characterized by a sudden decrease in vision or even vision loss in one eye.This article reports a case of central RAO caused by emboli through a branch of the external carotid artery during CAS,aiming to provide insights for optimizing CAS procedures,and preventing and controlling this complication.

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.