AIM:To investigate the effects of high-altitude hypoxic exposure on retinal injury and the associated changes in oxidative stress-related indicators in rats. METHODS: Twenty-four healthy male Sprague-Dawley(SD)rats were randomly divided into a plain group and a high-altitude group, with 12 rats(24 eyes)in each group. Rats in the plain group were housed under normoxic conditions in an SPF-grade animal facility, whereas rats in the high-altitude group were placed in a special environmental chamber simulating an altitude of 6 000 m for 7 d. Optical coherence tomography(OCT)was used to assess retinal layer architecture and quantify retinal thickness. Hematoxylin-eosin(HE)staining was performed to observe retinal histopathological changes. Immunofluorescence(IF)was used to detect the expression of hypoxia-inducible factor-1α(HIF-1α)in retinal tissue. Transmission electron microscopy(TEM)was applied to examine the ultrastructure of retinal ganglion cells(RGCs). Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of malondialdehyde(MDA), total superoxide dismutase(T-SOD), and reduced glutathione(GSH)in retinal tissue. In addition, intracellular reactive oxygen species(ROS)levels in retinal tissue were assessed using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe. RESULTS: OCT examination revealed disorganized retinal architecture in the high-altitude group, with increased inner and middle ring thickness and decreased outer ring thickness compared with the plain group(all P<0.05). HE staining showed varying degrees of retinal layer damage, blurred layer boundaries, loosely arranged RGCs, and partial cellular necrosis in the high-altitude group. IF analysis demonstrated significantly increased HIF-1α expression in the inner nuclear layer of the high-altitude group(P<0.01). TEM revealed mitochondrial swelling, disrupted cristae, and reduced matrix electron density in RGCs of the high-altitude group. ELISA and fluorescence probe assays showed significantly elevated MDA levels and ROS fluorescence intensity, accompanied by decreased T-SOD and GSH levels in the retinal tissue of the high-altitude group(all P<0.05). CONCLUSION: Exposure to a high-altitude hypoxic environment induces marked morphological and ultrastructural damage in the rat retina and significantly enhances oxidative stress, suggesting that oxidative stress may play a critical role in retinal injury induced by high-altitude hypoxia.

Objective To investigate the lifestyle and cardiovascular disease in the elderly and analyze their association. Methods A simple random sampling method was used to select the elderly aged 60 years and above in a community of Xining from September 2022 to September 2023 as the study subjects. General demographic characteristics, prevalence of cardiovascular disease, living habits and activity status were collected by questionnaire. Demographic characteristics and life behavior habits were compared between the diseased and non-diseased groups, and multivariate logistic regression was used to analyze the influencing factors of cardiovascular disease in the elderly. Results A total of 784 subjects, 259 (33.04%) suffered from cardiovascular disease, with coronary heart disease and hypertension being the most common. In terms of disease risk, males were 1.378 times higher than females, non-income groups were 1.394 times higher than income groups, receiving health education/popular science < 1 time/month groups were 1.533 times higher than ≥ 2 times/month groups, combined diabetes or obesity groups were 1.490 times and 1.470 times higher than non-diabetes or obesity groups, salty fresh taste groups were 1.690 times higher than light taste groups, fresh fruit intake frequency ≤ 3 times/week groups were 1.492 times higher than ＞7 times/week groups, smoking ≥ 30 cigarettes/month groups were 2.257 times higher than non-smoking groups, drinking ≥ 2 liquors or 500 ml beer/day groups were 1.569 times higher than non-drinking groups, irregular physical examination habits groups were 1.619 times higher than regular physical examination habits groups, aerobic exercise did not reach the standard groups were 1.454 times higher than the standard groups. Conclusion Lifestyle is associated with cardiovascular disease in the elderly. It is important to carry out targeted health education and advocate healthy behavior lifestyle to prevent and treat cardiovascular disease.

ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

BACKGROUND

Due to the COVID-19 outbreak, schools had to switch online. The sudden transition to blended teaching and learning (BTL) poses challenges for students and teachers, especially for health science programs that require hands-on practical experience. The validity, reliability, and responsiveness of these self-report questionnaires (SRQs) should be established to ensure the accuracy of the results as intended by the SRQ.

This study critically appraised, compared, and summarized the psychometric properties of SRQ evaluating BTL among health science university students. This review determined the SRQ’s reliability, internal consistency, various forms of validity (content, criterion, construct), and responsiveness.

Following a 10-step procedure based on COSMIN guidelines, we conducted a systematic review of SRQs used by health science university students to evaluate blended teaching and learning. Studies were eligible if they reported psychometric properties of SRQs related to blended learning among university health science students; exclusions included studies focusing on perceptions, attitudes, self-efficacy, and satisfaction, as well as articles such as biographies, editorials, and conference materials. Searches covered multiple electronic databases until April 26, 2023, including PubMed, EMBASE, Web of Science, MEDLINE (OVID), PsycInfo, CINAHL, EBSCOHOST, ERIC, Scopus, Science Direct, Google Scholar, JSTOR, Acta Medica Philippina, Philippine Journal of Health Research and Development, and HERDIN, managed through Zotero. Two independent reviewers performed database searches, title and abstract screening, and full-text evaluations, with a third reviewer resolving any disputes. The COSMIN Risk of Bias Checklist was employed to evaluate included studies on the development and various measurement properties of SRQs. The reviewers assessed SRQ standards, including validity, reliability, internal consistency, measurement error, responsiveness, interpretability, and feasibility. Data extraction and result tabulation were independently completed, with content comparison by two health education experts. This evaluation categorized the SRQs into three quality and validity levels.

The study examined five articles; four were rated as 'doubtful' and one as 'inadequate' in the overall development of SRQ. All four 'doubtful' studies demonstrated questionable content validity when university students were asked about the questionnaire's relevance, comprehensiveness, and comprehensibility. Only half of these studies achieved an 'adequate' rating for content validity based on expert opinions on relevance and comprehensiveness. All but one study scored from 'very good' to 'adequate' in structural validity. Three out of the four studies scored a very good rating for internal consistency, while one was deemed 'inadequate' in internal consistency, cross-cultural validity, and reliability. Three out of four studies scored 'very good' on construct validity, but all overlooked criterion validity and responsiveness. Conducted in various locations, including Australia, Romania, Turkey, and Taiwan, these studies highlighted both common characteristics and limitations in questionnaire development according to the COSMIN guidelines. Four studies were deemed reliable and valid for BTL constructs (Category A); Wu et al. requires further validation (Category B). Study limitations included heterogeneity in populations, settings, and questionnaire versions, potential subjective bias in SRQ content comparison, and the evolving nature of SRQs in blended learning contexts.

The systematic review reports the development and evaluation of SRQs for BTL while identifying gaps in their applicability to health science programs. The Blended Learning Scale (BLS) of Lazar et al. and the Blended Learning Questionnaire (BLQ) of Ballouk et al. showed an ‘adequate' rating for content validity. BLS revealed very good structural validity, internal consistency, and adequate content validation. Although the BLQ lacked Confirmatory Factor Analysis, it yielded valuable constructs for evaluating health sciences students' experiences in BTL. Both tools require improvements on recall period, completion time, interpretability, and feasibility. The review underscores the necessity for cont inuous assessment and enhancement of such instruments in BTL, advocating a rigorous scale development process. Furthermore, it encourages the customization of teaching and learning evaluation tools to suit specific institutional contexts while promoting further validation of these questionnaires across different populations in future research.

BACKGROUND

Due to the COVID-19 outbreak, schools had to switch online. The sudden transition to blended teaching and learning (BTL) poses challenges for students and teachers, especially for health science programs that require hands-on practical experience. The validity, reliability, and responsiveness of these self-report questionnaires (SRQs) should be established to ensure the accuracy of the results as intended by the SRQ.

This study critically appraised, compared, and summarized the psychometric properties of SRQ evaluating BTL among health science university students. This review determined the SRQ’s reliability, internal consistency, various forms of validity (content, criterion, construct), and responsiveness.

Following a 10-step procedure based on COSMIN guidelines, we conducted a systematic review of SRQs used by health science university students to evaluate blended teaching and learning. Studies were eligible if they reported psychometric properties of SRQs related to blended learning among university health science students; exclusions included studies focusing on perceptions, attitudes, self-efficacy, and satisfaction, as well as articles such as biographies, editorials, and conference materials. Searches covered multiple electronic databases until April 26, 2023, including PubMed, EMBASE, Web of Science, MEDLINE (OVID), PsycInfo, CINAHL, EBSCOHOST, ERIC, Scopus, Science Direct, Google Scholar, JSTOR, Acta Medica Philippina, Philippine Journal of Health Research and Development, and HERDIN, managed through Zotero. Two independent reviewers performed database searches, title and abstract screening, and full-text evaluations, with a third reviewer resolving any disputes. The COSMIN Risk of Bias Checklist was employed to evaluate included studies on the development and various measurement properties of SRQs. The reviewers assessed SRQ standards, including validity, reliability, internal consistency, measurement error, responsiveness, interpretability, and feasibility. Data extraction and result tabulation were independently completed, with content comparison by two health education experts. This evaluation categorized the SRQs into three quality and validity levels.

The study examined five articles; four were rated as 'doubtful' and one as 'inadequate' in the overall development of SRQ. All four 'doubtful' studies demonstrated questionable content validity when university students were asked about the questionnaire's relevance, comprehensiveness, and comprehensibility. Only half of these studies achieved an 'adequate' rating for content validity based on expert opinions on relevance and comprehensiveness. All but one study scored from 'very good' to 'adequate' in structural validity. Three out of the four studies scored a very good rating for internal consistency, while one was deemed 'inadequate' in internal consistency, cross-cultural validity, and reliability. Three out of four studies scored 'very good' on construct validity, but all overlooked criterion validity and responsiveness. Conducted in various locations, including Australia, Romania, Turkey, and Taiwan, these studies highlighted both common characteristics and limitations in questionnaire development according to the COSMIN guidelines. Four studies were deemed reliable and valid for BTL constructs (Category A); Wu et al. requires further validation (Category B). Study limitations included heterogeneity in populations, settings, and questionnaire versions, potential subjective bias in SRQ content comparison, and the evolving nature of SRQs in blended learning contexts.

The systematic review reports the development and evaluation of SRQs for BTL while identifying gaps in their applicability to health science programs. The Blended Learning Scale (BLS) of Lazar et al. and the Blended Learning Questionnaire (BLQ) of Ballouk et al. showed an ‘adequate' rating for content validity. BLS revealed very good structural validity, internal consistency, and adequate content validation. Although the BLQ lacked Confirmatory Factor Analysis, it yielded valuable constructs for evaluating health sciences students' experiences in BTL. Both tools require improvements on recall period, completion time, interpretability, and feasibility. The review underscores the necessity for cont inuous assessment and enhancement of such instruments in BTL, advocating a rigorous scale development process. Furthermore, it encourages the customization of teaching and learning evaluation tools to suit specific institutional contexts while promoting further validation of these questionnaires across different populations in future research.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.