Objective To determine the effect of unfractionated heparin (UFH) on lipopolysaccharide (LPS)-induced expression of chemokines and nuclear factor-κB (NF-κB) signaling pathway. Methods Human pulmonary microvascular endothelial cells (HPMECs) were cultured in vitro, and the cells between passages 3 and 5 were used in the experiments. The cells were divided into control group, LPS challenge group, 1 kU/L or 10 kU/L UFH+LPS group, and NF-κB inhibitor N-tosyl-L-lysyl chloromethyl-ketone (TLCK) group (TLCK+LPS group). HPMECs in LPS challenge group were treated with 10 mg/L LPS. UFH pretreatment with different dosages groups were treated with 1 kU/L or 10 kU/L UFH 15 minutes before LPS challenge. Cells in the TLCK+LPS group were treated with 10 μmol/L of TLCK 30 minutes before the addition of LPS, and HPMECs in control group were treated with an equal volume of phosphate-buffered saline (PBS) instead. The cells were harvested 1 hour after LPS challenge, and the nuclear translocation of NF-κB was determined by immunofluorescence assay to detect the effect of UFH on NF-κB activation. The levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cell culture supernatants were determined by enzyme linked immunosorbent assay (ELISA) 3 hours and 6 hours after LPS challenge to detect the effect of UFH on LPS induced expression of chemokines and its mechanism of effect on NF-κB signaling pathway in HPMECs. Results ① In the control group, NF-κB was mostly located in the cytosol as shown by immunofluorescence. Treatment of HPMECs with LPS significantly increased the translocation of NF-κB from the cytosol to nucleus. UFH suppressed LPS-induced NF-κB activation both in 1 kU/L and 10 kU/L dosages, and 10 kU/L UFH gave even better results. ② Compared with control group, the levels of IL-8 and MCP-1 in the supernatants in LPS challenge group were significantly increased at 3 hours and 6 hours after LPS challenge [IL-8 (ng/L): 387.1±26.4 vs. 23.8±8.1 at 3 hours, 645.5±69.6 vs. 125.7±18.7 at 6 hours; MCP-1 (ng/L): 3 654.9±467.9 vs. 721.6±61.3 at 3 hours, 8 178.5±792.6 vs. 1 324.7±148.7 at 6 hours, all P < 0.05]. Compared with that of LPS challenge group, in 1 kU/L and 10 kU/L UFH pretreatment groups, the levels of IL-8 and MCP-1 were significantly decreased [IL-8 (ng/L): 315.3±24.8, 275.8±31.1 vs. 387.1±26.4 at 3 hours, 557.8±43.3, 496.9±38.7 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 2 924.1±267.9, 2 668.3±522.6 vs. 3 654.9±467.9 at 3 hours, 7 121.7±557.2, 6 563.9±576.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. The results indicated that 10 kU/L UFH yielded better results. However, inhibition study using the known NF-κB inhibitor TLCK could decrease LPS-induced increase in IL-8 and MCP-1 levels [IL-8 (ng/L): 162.4±21.3 vs. 387.1±26.4 at 3 hours, 274.1±22.6 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 1 478.2±138.5 vs. 3 654.9±467.9 at 3 hours; 3 667.6±259.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. Conclusions The levels of IL-8 and MCP-1 were increased obviously in LPS treated HPMECs. UFH might suppress LPS-activated NF-κB signaling pathway, contributing to the inhibitory effects of chemokines in HPMECs.

Objective To study the browning-related genes of Poria cocos mycelia,so as to provide a basis for their further verification and to discuss the browning molecular mechanism of Poria cocos.Methods Four samples of normal and brown Poria cocos mycelia were analyzed by transcriptome sequencing.After aligned with the reference genome sequence of Poria cocos,the expression levels of the genes in different samples were analyzed.Results A total of 12 383 transcripts were identified.Among them,1 017 genes were firstly found,and 260 genes were functionally annotated.Based on the alignment results,336 common differentially-expressed genes overlapped between the normal mycelia and 3 browned mycelia were obtained,and part of them were evaluated.Conclusion Transcriptome sequencing results showed that plenty of differentially-expressed genes were found in brown Poria cocos mycelia,and the difference of the expression levels of some genes was up to several hundred folds or even thousands of folds,whose related-functions were worth of further analysis.

Using novel virtual reality (VR) technology to carry out the construction of clinical medical examination question bank, while deepening the reform of clinical medical course examination, it continues to innovate the medical professional evaluation system and improve the flexibility, diversity and scientificity of clinical medicine in teaching and assessment. It is of great and far-reaching significance to improve the teaching level and the quality of medical education in medical colleges and universities. This paper analyzes and discusses the necessity and feasibility of building a clinical medical examination question bank, and the advantages and prospects of integrating VR technology to carry out the construction of clinical medical examination question bank. At the same time, the exploration and practice of the examination question bank construction based on VR technology disscussed in detail would provide innovative thinking and reference for the clinical medical teaching and evaluation, medical personnel training and other aspects in China.

Objective:To investigate the expression level of flap endonuclease 1 (FEN1) in bone marrow mononuclear cells of patients with acute myeloid leukemia (AML) and its relationship with clinicopathologic features and therapeutic effect, so as to provide a new direction for disease monitoring and targeted therapy in AML patients.Methods:The data of 57 newly treated AML patients and 26 healthy individuals (the healthy control) from the First Clinical College of Guangdong Medical University and Fujian Medical University Union Hospital from November 2018 to December 2020 were retrospectively analyzed. Bone marrow samples of all subjects were collected. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was used to detect FEN1 mRNA expression in bone marrow mononuclear cells of all subjects. Bone marrow samples from 9 newly-diagnosed AML patients and 4 healthy controls were collected, and FEN1 protein expression level was detected by using Western blotting. Differences in FEN1 mRNA expression in AML patients achieving different therapeutic effects were compared among AML patients whose data with evaluable efficacy. AML patients were divided into high FEN1 expression group (≥ critical value) and low FEN1 expression group (< critical value), taking the median relative expression level of FEN1 mRNA as the critical value. The correlation of FEN1 expression level with clinicopathologic features, laboratory indicators, cellular and molecular genetic changes in AML patients at initial diagnosis was analyzed.Results:The median relative expression of FEN1 mRNA in newly treated AML patients was higher than that in healthy controls [0.696 (0.025-3.661) vs. 0.246 (0.013-1.237), Z = 1.75, P = 0.041]. Western blotting showed that the expression level of FEN1 protein in AML patients was higher than that in healthy controls. The relative expression of FEN1 mRNA in 15 recurrent AML patients was higher than that in 19 patients patients achieving complete remission (CR) [1.153 (0.047-4.172) vs. 0.259 (0.023-1.148), Z = 2.71, P = 0.009]. The proportion of patients with French-American-British(FAB) type M 5, fever at initial diagnosis and lymph node enlargement in FEN1 high expression group (32 cases) was higher than that in FEN1 low expression group (25 cases) (all P < 0.05). There were no significant differences in the proportion of gender, age, fatigue, pale skin mucosa and large liver and spleen of patients between the two groups (all P > 0.05). At initial diagnosis, the white blood cell count, lactate dehydrogenase, C-reactive protein and bone marrow primitive cell proportion in FEN1 high expression group were higher than those in FEN1 low expression group (all P < 0.05), and the hemoglobin and platelet count in FEN1 high expression group were lower than those in FEN1 low expression group (all P < 0.05). There were no significant differences in procalcitonin level, the proportion of chromosome karyotype, cytogenetic prognosis grade and patients with or without gene mutation between the two groups (all P > 0.05). Conclusions:FEN1 expression is up-regulated in AML patients and further increased in relapsed patients. FEN1 expression in AML patients is associated with adverse clinicopathological features and poor detection results of laboratory indicators, which may become indicators for disease monitoring in AML patients.

Objective:To investigate the expression level of small nucleolar RNA SNORD15A in bone marrow of patients with acute leukemia (AL) and its relationship with clinical characteristics and prognosis of patients.Methods:Bone marrow blood samples of 53 newly treated AL patients and 29 healthy subjects without clinical diagnosis of hematologic diseases or other malignant diseases (control group) at the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of SNORD15A in bone marrow blood mononuclear cells of the two groups. The median relative expression of SNORD15A (0.148) was used as the boundary, and AL patients were divided into low expression group (<0.148) and high expression group (≥0.148). The relationship between the expression level of SNORD15A and the clinical characteristics, clinical indicators and overall survival (OS) of AL patients was analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was performed; Cox proportional hazards model was used for univariate and multivariate analyses of OS of patients.Results:The relative expression of SNORD15A was 0.148 (0.012-1.376) in newly treated AL patients and 0.921 (0.513-2.288) in the control group, and the difference was statistically significant ( Z = -6.85, P < 0.01). The differences in SNORD15A relative expression between patients with different prognostic stratification, efficacy and with or without fever and bleeding were statistically significant (all P < 0.05). The differences in platelet count, plateletcrit and albumin levels between SNORD15A low expression group and high expression group were statistically significant (all P < 0.05), and the differences in molecular biology and cytogenetic characteristics were not statistically significant (all P > 0.05). The patients in SNORD15A high expression group had better OS than the low expression group ( P < 0.05). The results of univariate Cox regression analysis showed that SNORD15A was an influencing factor for patients' OS ( HR = 0.063, 95% CI 0.005-0.766, P < 0.05); the results of multivariate Cox regression analysis showed that fatigue ( HR = 4.754, 95% CI 1.014-22.290), fever ( HR = 0.147, 95% CI 0.029-0.746) and hemoglobin ( HR = 0.970, 95% CI 0.944 -0.998) were independent influencing factors for OS (all P < 0.05). Conclusions:SNORD15A is lowly expressed in AL and may be an indicator for disease monitoring and prognostic assessment in AL patients.

Cerebral microbleed (CMB) is a type of cerebral small vessel disease (CSVD). Recently studies have found that there is a certain relationship between CMB and cognitive impairment. This article mainly reviews the etiology of CMB, the relationship between CMB and cognitive impairment, CMB and cognitive disorders and the possible mechanism of CMB-related cognitive impairment, in order to improve the understanding of cognitive impairment caused by CMB.

Objective To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People′s Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m2, (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m2, (6.7±1.6) mmol/L, (6.1± 1.2) mmol/L; (22±3) kg/m2, (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM ( OR=2.799, 95% CI :1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.

Objective:To investigate and analyze the status quo of death cognition and hospice care attitude of clinical medical graduate students, to compare the differences between the two groups, and to explore the correlation between death cognition and hospice care attitude, so as to provide the reference for the reform and construction of death cognition and hospice care education in medical colleges and universities in China.Methods:A survey was carried out on 496 doctoral and postgraduate students majoring in clinical medicine by using the "Questionnaire of General Sociology Survey", the Chinese version of the "Death Attitude Profile Revised Scale", and the Chinese version of the "Frommelt Attitudes Toward Care of the Dying Scale Form B (FATCOD-B)" to investigate the death cognition and hospice care attitude of 496 doctoral and postgraduate students majoring in clinical medicine, and classified and compared the survey results of the two groups. The results of this study were statistically analyzed by t-test, Pearson correlation analysis and other statistical methods. Results:A total of 469 valid questionnaires were recovered after excluding 27 unqualified questionnaires. Statistical analysis showed that the scores of each dimension in the death attitude description scale of doctoral students were ranked as follows: approach acceptance (4.28±0.53), neutral acceptance (3.99±0.41), death avoidance (2.74±0.63), fear of death (2.65±0.57) and escape acceptance (2.47±0.69) the scores of postgraduates were ranked as neutral acceptance (3.96±0.52), approach acceptance (2.84±0.61), fear of death (2.78±0.65), death escape (2.62±0.73), escape acceptance (2.39±0.77). At the same time, the scores of hospice care attitude in the doctoral group were higher than those in the master group [(110.63±8.96) vs. (106.78±6.52)], and the difference was statistically significant ( P<0.001). In addition, the scores of "fear of death" and the scores of hospice care attitudes were negatively correlated with the scores of doctoral and master students ( r=-0.25, r=-0.21), while the scores of hospice care attitudes were positively correlated with the scores of "neutral acceptance" in death cognition ( r=0.50, r=0.32). However, the hospice care attitude scores of doctoral students were negatively correlated with the "death avoidance" scores in death cognition ( r=-0.27). Conclusion:Doctoral and postgraduate students have a certain awareness of hospice care, while their death cognition and hospice care attitude still need to be improved and strengthened from sociology, psychology, ethics and other perspectives. The above will promote the harmony between doctors and patients while meeting the needs of an aging society in China.

Objective: To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods: A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People's Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results: (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m², (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m², (6.7±1.6) mmol/L, (6.1±1.2) mmol/L; (22±3) kg/m², (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM (OR=2.799, 95%CI: 1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.