Objective To investigate the effect and molecular mechanism of safflower yellow(SY)on wound healing of diabetic foot ulcer(DFU)in mice.Methods Forty-five C57BL/6 mice were injected intraperitoneally with streptozotocin to establish diabetic models.The diabetic mice were randomly divided into the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with insulin-like growth factor-1(IGF-1)group,with 9 mice in each group.Before modelling,mice in the model group were not given any intervention,mice in the low-dose SY intervention group and high-dose SY intervention group were injected intraperitoneally with 5 and 20 mg·kg-1 SY,respectively,and mice in the high-dose SY combined with IGF-1 group were injected intraperitoneally with 20 mg·kg-1 SY and 0.03 mg·kg-1 IGF-1.Except for the sham operation group,the DFU model was established by incising the dorsal skin of the foot in the remaining four groups of mice.No wound on the dorsal skin of the foot was made in the sham operation group,and the remaining surgical steps were the same as those in the model group.The body mass of mice in each group was measured on day 14 after modelling using an electronic scale,tail vein blood was collected for fasting blood glucose measurement,and the wound width was measured using a small vernier caliper.Then,the mice were executed to collect the wound tissues.Hematoxylin-eosin staining was used to detect the histopathological changes in the wound tissues of mice in each group.Reverse transcription-quantitative real-time polymerase chain reaction was used to measure the relative expression levels of platelet-derived growth factor(PDGF),vascular endothelial growth factor(VEGF),alpha-smooth muscle actin(α-SMA),type Ⅰ collagen(collagen Ⅰ),protein tyrosine phosphatase 1B(PTP1B)and advanced glycation end products(AGEs)mRNA in the wound tissues of mice in each group.Western blot was used to detect the relative expression levels of proliferation marker Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-associated proteins(caspase-3,caspase-6,and caspase-7),p85 phosphatidylinositol-3-kinase(PI3K)and phosphorylated protein kinase B(p-AKT)protein in the wound tissues of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in the wound tissues of mice in each group.Results The differences in blood glucose and body mass of mice among the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with IGF-1 group were not statistically significant(P＞0.05).The healing rate of wound tissues in the high-dose SY intervention group was significantly greater than that in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the healing rate of wound tissues among the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＞0.05).In the high-dose SY intervention group,a large number of collagen fibers were densely and orderly arranged in the wound tissues,accompanied by a large number of neovessels;in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group,the wound tissues were sparsely populated with collagen fibers,accompanied by a small number of neovessels.The relative expression levels of PDGF,VEGF,α-SMA and collagen Ⅰ mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expression levels of PTP1B and AGEs mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).The relative expression levels of PDGF,VEGF,α-SMA,collagen Ⅰ,PTP1B and AGEs mRNA showed no statistically significant difference among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The relative expression levels of Ki-67 and PCNA protein in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expre-ssion levels of caspase-3,caspase-6,caspase-7,p85 PI3K,and p-AKT protein were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the relative expression levels of Ki-67,PCNA,caspase-3,caspase-6,caspase-7,p85 PI3K and p-AKT protein among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＜0.01).There was no statistically significant difference in the levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the model,low-dose SY intervention and high-dose SY combined with IGF-1 groups(P＞0.05).Conclusion High-dose SY intervention promotes DFU wound healing in mice by increasing angiogenesis,collagen formation and cell proliferation and reducing insulin resistance,inflammatory response and cell apoptosis,which may be related to the inhibition of the PI3K/AKT pathway.

Lambert-Eaton myasthenic syndrome(LEMS)is an immune-mediated disorder involving neuromuscular junctions,characterized by muscle weakness,autonomic dysfunction,and reduced tendon reflexes.We report a LEMS case presented initially with dizziness and ataxia,followed by eyelid ptosis.Repetitive nerve stimulation revealed low frequency decreasing and high frequency increasing.P/Q type Voltage-gated calcium channels(VGCC)antibody was positive.Chest CT showed pulmonary nodules and enlarged mediastinal lymph nodes which were pathologically confirmed as small cell lung cancer.Given that ataxia is also an important manifestation of LEMS,the case report intends to increase the awareness of LEMS-related ataxia among neurologists to avoid misdiagnosis.

Objective:To analyze the characteristics of accidental injury death among Chinese population from 2005 to 2021 and predict its trends from 2022 to 2031.Methods:Based on the China Death Surveillance Database, the accidental injury death data of Chinese population from 2005 to 2021 were collected. The overall accidental injury death of Chinese population during the period was calculated, such as crude mortality rate and standardized mortality rate. A Joinpoint regression model was applied to calculate the standardized mortality rate including the annual percentage change (APC) and average annual percentage change (AAPC) of accidental injury death among Chinese population of different genders, in urban and rural areas, age groups and eastern, central and western regions from 2005 to 2021. The standardized mortality rate of accidental injuries among Chinese population from 2022 to 2031 was predicted by using the exponential smoothing method. Results:From 2005 to 2021, the crude mortality rate of accidental injury among Chinese population decreased from 45.96/100 000 in 2005 to 39.97/100 000 in 2021, with the standardized mortality rate decreasing from 50.20/100 000 in 2005 to 30.74/100 000 in 2021, which showed a monotonous downward trend (APC=AAPC=-2.63, P<0.01). From 2005 to 2021, the standardized mortality rate of accidental injury in males was higher than that in females, showing a downward trend in both males and females (AAPC male=-2.85, AAPC female=-2.17, P<0.01) . From 2005 to 2021, the standardized mortality rate of accidental injury in rural population was higher than that in urban population, showing a downward trend in both urban and rural population (AAPC city=-2.39, P<0.01; AAPC rural=-2.58, P<0.05). From 2005 to 2021, the standardized mortality rate of accidental injury in Chinese population mainly fell in the age group of 15-44 years. From 2005 to 2021, the standardized mortality rate of accidental injury in the western region was higher than that in the eastern and central regions and there was an inflection point from up to down in the standardized mortality rate of accidental injury in the western and central regions in 2011. As the forecasting results showed, the standardized mortality rate of accidental injury among Chinese population would be reduced from 30.26/100, 000 to 20.93/100, 000 from 2022 to 2031. Conclusions:The standardized mortality rate of accidental injury among Chinese population from 2005 to 2021 shows a downward trend. Moreover, the male, rural, young and middle-aged population and population in the western region are still the key groups needing prevention of accidental injuries. There will also be a downward trend in the standardized mortality rate of accidental injuries in Chinese population from 2022 to 2031.

Objective:To analyze the mortality of accidental falls among the elderly in China from 2004 to 2019 and predict the standardized mortality from 2020 to 2024, so as to provide scientific evidence for formulating strategies to prevent accidental falls among the elderly.Methods:The death data of accidental falls of the elderly in China from 2004 to 2019 were collected from the China Death Cause Monitoring Data Set, and the total number of deaths, mortality rate and standardized mortality rate in the elderly from 2004 to 2019 and those data among them of different genders, residences and age groups were calculated. Joinpoint 4.8.0.1 statistical software was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of standardized mortality. The Autoregressive Integrated Moving Average Model (ARIMA) was used to predict the standardized mortality rate of accidental falls among the elderly in China from 2020 to 2024. Results:The number of deaths related to accidental falls among the elderly in China was increased from 2 908 in 2004 to 23 709 in 2019. The mortality rate was increased from 51.89/100 000 in 2004 to 67.74/100 000 in 2019. The standardized mortality rate of accidental falls showed an overall upward trend from 2004 to 2019 (AAPC=1.65, P>0.05), including an upward trend from 2004 to 2010 (APC=1.66, P>0.05), a downward trend from 2010 to 2013 (APC=-9.67, P>0.05), and another upward trend from 2013 to 2019 (APC=7.83, P<0.01). The number of death and mortality rate related to accidental falls in Chinese elderly males and females both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed upward trends from 2004 to 2019 (AAPC males=2.19, AAPC females=0.29, all P>0.05). The standardized mortality rate in males was generally higher than that in females, with that of males showing an upward trend from 2013 to 2019 (APC=7.36, P<0.05) and that of female showing an upward trend from 2014 to2019 (APC=6.92, P>0.05). The number of deaths and mortality rate among the elderly living in rural and urban areas both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed an upward trend from 2004 to 2019 (AAPC rural = 1.71, AAPC urban =1.00, all P>0.05). The standardized mortality rate among the elderly living in rural areas was generally higher than that in urban areas. The rural and urban elderly both showed upward trends from 2013 to 2019 (APC rural = 8.24, APC urban =6.11, all P<0.05). The number of death and mortality rate of different age groups all showed upward trends from 2004 to 2019. The standardized mortality rates of the elderly aged 65-74 years and ≥85 years also showed upward trends from 2004 to 2019 (AAPC 65-74 years=0.38, AAPC ≥ 85 years=4.09, all P>0.05). The standardized mortality rate of the elderly aged 75-84 years showed a downward trend from 2004 to 2019 (AAPC=-0.10, P>0.05), and that of the elderly aged 65-74 years showed an upward trend from 2010 to 2019 (APC=5.35, P<0.05). The standardized mortality rate of the elderly aged 75-84 years and ≥85 years showed upward trends from 2013 to 2019 (APC 75-84 years=6.49, APC ≥ 85 years=10.47, all P<0.05). The ARIMA prediction results showed that the overall standardized mortality rates of accidental falls in the elderly in China from 2020 to 2024 were 69.11/100 000, 72.33/100 000, 74.41/100 000, 76.34/100 000, and 76.48/100 000, respectively, showing a slow upward trend. Conclusions:The accidental fall-related mortality among the elderly in China showed an overall upward trend from 2004 to 2019, and the standardized mortality rate from 2020 to 2024 also shows an upward trend. The elderly who are male in gender, live in rural areas, or at age of ≥85 years are the key population for prevention and control of accidental fall. Active and effective measures should be taken to reduce accidental falls in the elderly so as to contribute to active and healthy aging.

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.

Objective To evaluate the protective effect of nuclear factor E2-related factor 2(Nrf2) protein against ultraviolet B (UVB)-induced photodamage to HaCaT cells,and to explore its mechanisms.Methods Cultured HaCaT cells were divided into 4 groups:control group receiving no treatment,UVB group irradiated with 30 mJ/cm2 UVB for 30 s,Nrf2 group transfected with a lentiviral vector overexpressing the Nrf2 gene,and Nrf2 + UVB group transfected with a lentiviral vector overexpressing the Nrf2 gene followed by radiation with 30 mJ/cm2 UVB for 30 s.After the treatment,HaCaT cells in the above 4 groups were cultured for another 24 hours.Then,changes in the morphology of HaCaT cells were observed after UVB radiation,Western blot analysis was performed to determine Nrf2 protein expression,cell counting kit-8 (CCKS) assay to detect survival rates of HaCaT cells,flow cytometry to detect levels of reactive oxygen species (ROS),and a biochemical method to detect superoxide dismutase (SOD) levels in cells,and enzyme-linked immunosorbent assay to detect levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the culture supematant of HaCaT cells.One-way analysis of variance was used for comparing means in several groups,and least significant difference (LSD)-t test for multiple comparisons.Results Polygonal and clustered HaCaT cells were observed in the control group.After UVB radiation,HaCaT cells became shrunken and round,the number of floating cells increased,and the number of adherent cells markedly decreased.There was a significant difference in Nrf2 protein expression among the control group,UVB group,Nrf2 group and Nrf2 + UVB group (1.84 ± 0.047,0.63 ± 0.082,2.19 ± 0.168 and 1.43 ± 0.069 respectively;F =64.81,P ＜ 0.05),and the Nrf2 protein expression was significantly higher in the Nrf2 group than in the control group (t =14.82,P ＜ 0.05);the survival rates of HaCaT cells also significantly differed among the above 4 groups (98.00％ ± 2.39％,24.40％ ± 2.98％,71.63％ ± 3.39％and 43.38％ ± 3.39％ respectively;F =236.66,P ＜ 0.05),and the UVB group showed significantly decreased cell viability compared with the control group (t =33.34,P ＜ 0.05)and Nrf2 + UVB group (t=10.07,P ＜ 0.05);a significant difference in the ROS level in HaCaT cells was observed among the above 4 groups (1.27 ± 0.10,5.65 ± 0.19,2.10 ± 0.73 and 3.67 ± 0.19 respectively;F =481.39,P ＜ 0.05),and the UVB group showed a significantly increased ROS level compared with the control group (t =33.68,P ＜0.05) and Nrf2 + UVB group (t =12.47,P ＜ 0.05).The SOD level in HaCaT cells significantly differed among the above 4 groups (F =170.76,P ＜ 0.05),and was significantly lower in the UVB group than in the control group (t =11.25,P ＜ 0.05) and Nrf2 + UVB group (t =17.52,P ＜ 0.05).The IL-6 level also significantly differed among the above 4 groups (F =532.34,P ＜ 0.05),and was significantly higher in the UVB group than in the control group (t =28.48,P ＜ 0.05) and Nrf2 + UVB group (t =27.82,P ＜ 0.05).There was no significant difference in the TNF-α level among the above 4 groups (F =2.02,P =0.19).Conclusion Nrf2 can protect HaCaT cells from UVB-induced oxidative damage,by reducing intracellular ROS levels and increasing the activity of the endogenous antioxidant enzyme SOD.

Brain glucose metabolism disorder is one of the pathophysiological features of Alzheimer's disease (AD), in which aerobic glycolysis (Warburg effect) metabolic pathway abnormality is one of the causes of early cognitive impairment in AD, and improving brain energy metabolism has become an important strategy to prevent AD. AMP-activated protein kinase (AMPK) is a central hub regulating glucose metabolism, the most sensitive molecular compound for sensing fluctuations of energy levels in the body. Activation of AMPK can affect the Warburg effect and its key rate-limiting enzyme activity, regulate brain glucose metabolism involved in the pathogenesis of AD, to achieve the purpose of delaying AD progression and improving cognitive function in early clinical stage. In this review, we will discuss the pathogenesis of AD and targeting of AMPK from the perspective of Warburg effect in glucose metabolism.

Objective:To explore the current status of clinical teaching staff for the graduate program of master of nursing specialist (abbreviated to nursing masters) in traditional Chinese medicine (TCM) universities and compare it with the role expectations of students, aiming to provide a reference for the subsequent construction and improvement of clinical teaching staff.Methods:Totally 172 nursing masters from Jiangsu, Zhejiang, Henan provinces and Tianjin and 86 clinical teaching staff from the hospitals where they practiced were selected using convenient samping and investigated with the self-made questionnaire from October to December 2018. The differences between clinical teaching staff's resources, abilities and students' expectations were compared. A total of 258 questionnaires were distributed among 86 clinical teachers and 172 nursing masters, and 258 valid questionnaires were recovered, with an effective rate of 100%. SPSS 22.0 software was used for statistical analysis of data.Results:There was a certain gap between the clinical teaching staff and students' expectations, especially in terms of the graduate school and academic qualifications of the clinical teachers. Totally 34.88% (30/86) of the clinical teachers graduated from TCM universities, while 71.51% (123/172) of the students expected to be taught by teachers graduating from TCM universities. Among the clinical teachers, 60.47% (52/86) were undergraduates, and fewer were masters or graduates with higher education. There was a certain difference between the teaching teachers' abilities and students' expectations. There were statistically significant differences in 17 secondary indicators (χ 2 were 12.027-130.149, P<0.05) , except for the professional attitude in clinical nursing abilities, decision-making abilities in clinical management abilities, communication abilities in interpersonal abilities, and collaboration abilities ( P>0.05) . There were statistically significant differences between students' current status and their learning needs for TCM nursing (χ 2 were 14.722-165.339, P<0.01) . TCM nursing skills and practical application of TCM nursing research were the contents that most students wanted to learn, accounting for 83.72% (144/172) and 70.35% (151/172) , respectively. Conclusions:There were differences between the current status of the teaching staff for nursing masters at TCM universities and the expectations of the students. The universities should fully consider the graduates' own expectations and needs based on the training objectives for graduates, actively explore the admission system for clinical teachers, improve the training system for teachers, and standardize the teaching evaluation mechanism based on the status quo of nursing talents in China.

To evaluate the cardiotoxicity of three novel proteasome inhibitors(NNU395, NNU458 and NNU459)in zebrafish, normal developmental zebrafish embryos at 6 hours post fertilization(hpf)were treated with different doses of NNU395 and NNU458 and NNU459 until 72 hpf, the zebrafish mortality was counted. Morphologic changes of the cardiovascular system were observed under a stereomicroscope, and the number of heart beats within 1 min was determined. The expression of cardiac development-related genes in zebrafish was detected by RT-qPCR(Quantitative Real-Time PCR). Results showed that NNU395, NNU458 and NNU459 increased the mortality of zebrafish in a concentration-dependent manner and the values of LC50(50% lethal concentration)were(179. 7±12. 2), (27. 5±1. 3)and(24. 4±2. 6)μmol/L, respectively. Moreover, the toxicity of our three compounds in zebrafish are less when compared with their modified precursors. Upon administration of NNU395 at the concentrations of 120- 200 μmol/L, and NNU458 or NNU459 at the concentration of 30 μmol/L, the zebrafish showed obvious pericardial edema cardiac malformation. 120- 200 μmol/L NNU395 and 0. 1- 30 μmol/L NNU458 or 10- 30 μmol/L NNU459 significantly reduced the heart rate of zebrafish. All of three compounds at the tested concentration had no significant effects on the expression of the heart development-related genes in zebrafish. Our results suggested that low concentrations of NNU395, NNU458 and NNU459 have no obvious toxicity on cardiac development of zebrafish. While, higher concentrations of them showed cardiovascular toxicity on zebrafish.

Objective To study the effect of baseline clinical characteristics of elderly female patients on their long-term ischemic cardiovascular events.Methods Of the 614elderly patients admitted to our center from April 2008to July 2010,144elderly female patients were divided into female cardiovascular events group(n=43)and female control group(n=101),470elderly male patients were divided into male cardiovascular events group(n=127)and male control group(n= 343).Their baseline clinical characteristics were compared.The patients were followed up for 4.5-6.7(5.6±0.9)years,during which the relationship between first ever acute ischemic cardiovascular events and their clinical factors were analyzed.Results The incidence of grade 2hypertension,grade 3hypertension and hypercholesterolemia,the ratios of antiplatelet drug therapy,CCB therapy and hypoglycemic drug therapy were significantly higher while the history of smoking was significantly shorter,the incidence of chronic renal insufficiency and the ratios of statins therapy,nitrates therapy and ACEI/ARB therapy were significantly lower in female patients than in male patients.The incidence of chronic renal insufficiency was significantly higher in female cardiovascular events group than in female control group(9.3％vs 1.0％,P=0.03).The age was significantly older,the incidence of CHD,ischemic cerebral stroke,chronic obstructive pulmonary disease and the ratio of nitrates therapy were significantly higher in male cardiovascular events group than in male control group.Cox multivariate regression analysis showed that the endpoint events were related with CHD,grade 2hypertension,grade 3hypertension,hypercholesterolemia,chronic renal insufficiency in female patients(HR=2.56,95％CI:1.19-5.54,P=0.017;HR=3.29,95％ CI:1.14-9.52,P=0.028;HR=2.77,95％CI:1.08-7.12,P=0.034;HR=2.61,95％CI:1.27-5.36,P=0.009;HR=22.70,95％CI:5.22-98.78,P=0.000)and were related with age,CHD and ischemic cerebral stroke in male patients(P＜0.05,P＜0.01).Conclusion The effect of baseline clinical characteristics of elderly patients on their long-term ischemic cardiovascular events is different in males and females.The incidence of long-term cardiovascular events is closely related with the risk factors for cardiovascular disease in elderly females.