Objective:To construct a new thrombus risk assessment model and evaluate its predictive ability for venous thromboembolism(VTE)in the patients with malignant tumors,and to provide the basis for the early predition of the malignant tumor patients with high risk for VTE.Methods:A total of 128 untreated malignant tumor patients were included,of which 40 were diagnosed with VTE within 2 months of malignant tumor diagnosis and categorized as VTE group.A total of 88 patients who did not develop VTE were categorized as non-VTE group.The clinical risk factors and laboratory indicators of the patients in two groups were compared and analyzed;the types of thrombotic events of the patients were analyzed;the diagnostic values of thrombin-antithrombin-complex(TAT),α2-plasmin inhibitor-plasmin complex(PIC),D-dimer(D-dimer),and fibrin degradation products(FDP)in malignant tumors complicated by VTE were assessed using receiver operating characteristic(ROC)curve analysis;Multivariate Logistic regression analysis was used to analyze the correlations of the clinical risk factors and biomarkers with the malignant tumors complicated with VTE.A new thrombus risk assessment model was constructed,consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors.The predictive probability of the model for malignant tumors complicated by VTE was evaluated based on the significance,goodness of fit,calibration curve,and C value of the model.The clinical application value of the new thrombus risk assessment model,COMPASS-CAT risk score(CRS),and Khorana risk score(KRS)in assessing malignant tumor patients complicated by VTE was compared using the C value and decision curve analysis(DCA).Results:The plasma levels of TAT(P＜0.001),PIC(P＜0.001),D-dimer(P＜0.05),and FDP(P＜0.01)of the patients in VTE group were higher than those in non-VTE group.Compared with the patients without cardiovascular risk factors,poor differentiation,and lymphatic metastasis,the malignant tumor patients with cardiovascular risk factors(P＜0.001),poor differentiation(P＜0.001),and lymphatic metastasis(P＜0.05)were more likely to develop VTE.Most VTE events(65％)were isolated deep vein thromboembolism(DVT).The ROC curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of TAT and PIC were higher than those of D-dimer and FDP.TAT≥0.70 μg·L-1(P＜0.05),poor differentiation(P＜0.01),and cardiovascular risk factors(P＜0.01)were the independent risk factors for VTE in the malignant tumor patients.A new thrombus risk assessment model consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors was constructed.The new risk assessment model had a high goodness of fit(P=0.805)and good predictive ability during internal validation(x2=75.266,P＜0.001).The ROC curve analysis results showed that the C values for the new thrombus risk prediction model,CRS,and KRS were 0.908,0.676,and 0.541,respectively.The DCA curve analysis results showed that the new thrombus risk assessment model had a higher net benefit rate compared with CRS and KRS.Conclusion:TAT and PIC have greater diagnostic efficiency than D-dimer in the early prediction of the malignant tumor patients with high-risk VTE.For the patients included in this study,the new thrombus risk assessment model,constructed from TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors,has superior diagnostic efficiency and clinical predictive value compared with CRS and KRS.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

Objective:To determine the expression of silent information regulator 1 (Sirt1) , Sirt3 and hypoxia-inducible factor 1α (HIF-1α) in cutaneous squamous cell carcinoma (CSCC) tissues and cells, and to explore their role in the occurrence and development of CSCC.Methods:From January 2019 to December 2020, 30 lesional skin tissues were obtained from patients with histopathologically confirmed poorly-, moderately- or well-differentiated CSCC, and 30 normal skin tissues were obtained from patients with non-cancerous diseases in Department of Dermatology, General Hospital of Ningxia Medical University. A CSCC cell line A431 and a human keratinocyte cell line HaCaT were cultured. Immunohistochemical study, Western blot analysis and real-time quantitative PCR (RT-PCR) were performed to determine the protein and mRNA expression of Sirt1, Sirt3 and HIF-1α in CSCC tissues of different grades of differentiation and normal skin tissues, cytochemical and immunofluorescence staining and RT-PCR were conducted to determine the protein and mRNA expression of Sirt1, Sirt3 and HIF-1α in A431 and HaCaT cells, respectively. Comparisons of measurement data among multiple groups were performed by using one-way analysis of variance, and comparisons between two groups by using t test. Results:Immunohistochemical study showed that the expression level of Sirt3 (expressed as the average optical density) was 100 ± 12.12, 117.72 ± 26.23, 127.32 ± 24.45, 132.71 ± 31.61 in the normal skin tissues and well-, moderately- and poorly-differentiated CSCC tissues respectively, and there was a significant difference among these groups ( F = 20.14, P < 0.001) ; the expression of Sirt1 and HIF-1α increased in turn from the normal skin tissues to the well-, moderately- and poorly-differentiated CSCC tissues, and significantly differred in these groups ( F = 174.50, 225.00, respectively, both P < 0.001) . As Western blot analysis revealed, the expression level of Sirt3 significantly differed among the normal skin tissues, well-, moderately- and poorly-differentiated CSCC tissues (expressed as relative gray value: 1.000 ± 0.132, 1.403 ± 0.411, 1.387 ± 0.393, 1.677 ± 0.683, respectively; F = 34.97, P < 0.001) , and so did the expression levels of Sirt1 and HIF-1α ( F = 69.29, 199.90, respectively, both P < 0.00l) , with a gradually increasing trend in their expression levels from the the normal skin tissues to well-, moderately- and poorly-differentiated CSCC tissues. RT-PCR showed that the mRNA expression of Sirt3, Sirt1 and HIF-1α was sequentially increased from the normal skin tissues to well-, moderately- and poorly-differentiated CSCC tissues, and significant differences were observed among these groups ( F = 113.00, 174.50, 50.33, respectively, all P < 0.001) . The protein expression levels of Sirt3, Sirt1 and HIF-1α were significantly higher in the A431 cells than in the HaCaT cells ( t = 16.75, 18.34, 27.76, respectively, all P < 0.001) , and so were their mRNA expression levels ( t= 14.22, 9.62, 16.86, respectively, all P < 0.001) . Conclusion:Increased expression of Sirt3, Sirt1 and HIF-1α was observed in CSCC tissues and cells, which may promote the occurrence and development of CSCC.

Objective:To study the illumination for distance vision evaluation of the pilots wearing night vision goggles (NVGs).Methods:The distance vision was tested by circular visual acuity chart for flying personnel 5 m apart from subjects. The Illuminance on the surface of chart was set 300 lx for naked eye and 1×10 -1 lx and 1×10 -3 lx for NVG aided eyes. The naked and NVG distance visions of 15 healthy male volunteers were tested under all illuminations. The differences of NVG distance vision were compared between the illuminations of 1×10 -1 lx and 1×10 -3 lx to determine the proper level for evaluation. The naked and NVG distance visions of 20 male pilots were tested to verify the feasibility and necessity of the test, but NVG tests were only at 1×10 -1 lx level. Results:Volunteers′ left distance vision was 0.67±0.39, the right was 0.67±0.38 and the binocular was 0.80±0.40. Their NVG distance vision under 1×10 -1 lx was 0.53±0.22, 0.59±0.25 and 0.63±0.24 respectively, comparing with the vision of 0.30±0.11, 0.34±0.11 and 0.36±0.11 under 1×10 -3 lx. The difference showed statistical significance ( P<0.05). In verification test, the left, right and binocular NVG distance vision of 20 pilots under 1×10 -1 lx was 0.63±0.16, 0.64±0.14 and 0.73±0.12 respectively, comparing with their left, right and binocular naked vision of 1.12±0.32, 1.08±0.37, and 1.37±0.37 respectively. Conclusions:The tests indicated that 1×10 -1 lx would be the appropriate illumination level for pilot′s NVG distance vision evaluation. And it is necessary to evaluate pilot′s NVG distance vision before night flight mission.

Objective:To study the illumination for distance vision evaluation of the pilots wearing night vision goggles (NVGs).Methods:The distance vision was tested by circular visual acuity chart for flying personnel 5 m apart from subjects. The Illuminance on the surface of chart was set 300 lx for naked eye and 1×10 -1 lx and 1×10 -3 lx for NVG aided eyes. The naked and NVG distance visions of 15 healthy male volunteers were tested under all illuminations. The differences of NVG distance vision were compared between the illuminations of 1×10 -1 lx and 1×10 -3 lx to determine the proper level for evaluation. The naked and NVG distance visions of 20 male pilots were tested to verify the feasibility and necessity of the test, but NVG tests were only at 1×10 -1 lx level. Results:Volunteers′ left distance vision was 0.67±0.39, the right was 0.67±0.38 and the binocular was 0.80±0.40. Their NVG distance vision under 1×10 -1 lx was 0.53±0.22, 0.59±0.25 and 0.63±0.24 respectively, comparing with the vision of 0.30±0.11, 0.34±0.11 and 0.36±0.11 under 1×10 -3 lx. The difference showed statistical significance ( P<0.05). In verification test, the left, right and binocular NVG distance vision of 20 pilots under 1×10 -1 lx was 0.63±0.16, 0.64±0.14 and 0.73±0.12 respectively, comparing with their left, right and binocular naked vision of 1.12±0.32, 1.08±0.37, and 1.37±0.37 respectively. Conclusions:The tests indicated that 1×10 -1 lx would be the appropriate illumination level for pilot′s NVG distance vision evaluation. And it is necessary to evaluate pilot′s NVG distance vision before night flight mission.

Objective: To investigate the relationship of sleep duration and sleep quality with anxiety in the elderly aged 60 years and older in China. Methods: The elderly aged 60 years and older were selected from the China Short-term Health Effects of Air Pollution Study conducted between July 18, 2017 and February 7, 2018. Multivariate logistic regression models were used to analyze the association of sleep duration and sleep quality with anxiety. Results: A total of 3 897 elderly aged 60 years and older were included in the study. The age of the elderly was (73.4±8.0) years old. Among the elderly surveyed, 6.5% were defined with anxiety, and 18.7% reported poor sleep quality. Multivariate logistic regression models showed shorter sleep duration was the risk factor for anxiety in the elderly that after adjusting for factors such as general demographics, socioeconomic factors, lifestyle, health status, social support and ambient fine particulates exposure. Compared with the elderly with 7 hours of sleep duration daily, the OR (95%CI) of anxiety for those with sleep duration ≤ 6 hours was 2.09 (1.49-2.93). Compared with those with good sleep quality, the OR (95%CI) of anxiety for those with poor sleep quality was 5.12 (3.88-6.77). We also found statistically significant correlations of the scores of subscales of Pittsburgh sleep quality index with anxiety, in which the effects of sleep disturbance, subjective sleep quality and daytime dysfunction scores were most obvious, the ORs (95%CI) were 4.63 (3.55-6.04), 2.75 (2.33-3.23) and 2.50 (2.19-2.86), respectively. Subgroup analysis showed that the association of sleep duration and sleep quality with anxiety was more obvious in males and in those aged <80 years. Conclusion Shorter sleep duration and poor sleep quality are associated with anxiety in the elderly in China.

Objective To build an analytic hierarchy process (AHP) of the medical selection for the high performance fighter pilot. Methods According to the consulting results from aeromedical experts ,an AHP model and expert′s judgment matrix were built and checked upon the consistency. Then ,the relative weights of evaluation indexes were calculated.The method was preliminarily applied in the medical selection of high performance fighter pilot. Results An AHP evaluation model of medical selection for high performance fighter pilot was constructed ,including 5 first level indexes of basic physiological function , flight physiological endurance , psychological basis , mental ability , physical fitness and ergonomics ,and 23 second level indexes.The relative weights of 5 first level indexes were 0.172 8 ,0.224 1 ,0.178 5 ,0.289 1 and 0.135 5 corresponding to basic physiological function ,flight physiological endurance , psychological basis , mental ability , physical fitness and ergonomics.The model was applied to comprehensively evaluate the physiological and psychological indexes of 16 hight performance fighter pilot candidates.The scores in turn from high to low were 7.79 ,7.45 ,7.24 ,7.17 ,7.15 ,6.92 ,6.81 ,6.59 ,6.24 ,6.02 ,5.96 ,5.85 ,5.83 ,5.71 ,5.26 and 5.20. Conclusions The AHP provides new method and reference to high performance fighter pilot selection and the application accumulates data and experience for other objective evaluation researches.

Objective To build an analytic hierarchy process (AHP) of the medical selection for the high performance fighter pilot. Methods According to the consulting results from aeromedical experts ,an AHP model and expert′s judgment matrix were built and checked upon the consistency. Then ,the relative weights of evaluation indexes were calculated.The method was preliminarily applied in the medical selection of high performance fighter pilot. Results An AHP evaluation model of medical selection for high performance fighter pilot was constructed ,including 5 first level indexes of basic physiological function , flight physiological endurance , psychological basis , mental ability , physical fitness and ergonomics ,and 23 second level indexes.The relative weights of 5 first level indexes were 0.172 8 ,0.224 1 ,0.178 5 ,0.289 1 and 0.135 5 corresponding to basic physiological function ,flight physiological endurance , psychological basis , mental ability , physical fitness and ergonomics.The model was applied to comprehensively evaluate the physiological and psychological indexes of 16 hight performance fighter pilot candidates.The scores in turn from high to low were 7.79 ,7.45 ,7.24 ,7.17 ,7.15 ,6.92 ,6.81 ,6.59 ,6.24 ,6.02 ,5.96 ,5.85 ,5.83 ,5.71 ,5.26 and 5.20. Conclusions The AHP provides new method and reference to high performance fighter pilot selection and the application accumulates data and experience for other objective evaluation researches.

Objective To evaluate the preventive effects of Haishe capsules on the conversion of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease(AD).Methods Patients (n=120) with aMCI from our department were recruited and randomly divided into the treatment group and the control group (n=60 in each group).The treatment group was given 0.9 gram of Haishe capsules three times a day while the control group received no drug treatment.Data on the conversion ratio,memory and cognitive function were comparedbetween the groups in a 24-months follow-up.Results By the end of the study,12 patients in the treatment group and 15 in the control group dropped out.Valid data for 93 patients were available for statistical analysis (48 in the treatment group and 45 in the control group).The number of aMCI patients who converted to AD was 6,with a conversion ratio of 12.5％ (6/48);and the number of patients who went through conversion in the control group was 13,with a conversion ratio of 28.8％ (13/45).The difference in conversion between the two groups was statistically significant (x2 =3.83,P＜0.05).After 24 months,MMSE scores for the treatment group (25.52± 1.07) had no significant change compared with baseline levels,while MMSE scores for the control group decreased significantly(24.75--1.49) and were markedly lower than thosefor the treatment group (t=2.85,P＜0.05).MoCA scores for the treatment group (19.39 ±2.01) did not show decline until the end of the study,while those for the control group started to decrease about half way through the study and were lower than scores for the treatment group (t =2.41,P＜0.05).Compared with baseline levels,ADAS-Cogscores for the treatment group (7.62± 1.06) did not increase significantly during the course of the study.ADAS-Cogscores forthe control group were higher at both half way (7.70±0.75) and the end of the study (8.18±0.80)than base line levels,and there was a statistically significant difference in end-of-study ADAS-Cog scores between the two groups(t =-2.6,P＜ 0.05).Conclusions Haishe capsules not only effectively maintain memory and cognitive function,but also delay the conversion from aMCI to AD.