Role of STAT3 activated NLRP3 inflammasomes in BV2 cell inflammatory response induced by maltol aluminum / 环境与职业医学

Background Aluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity. Objective To explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)3]. Methods BV2 cells were assigned to five groups: one control group, three Al(mal)3 exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L−1 Al(mal)3 respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L−1 C188-9 +160 μmol·L−1 Al(mal)3]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA. Results The results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)3 dose. Compared with the control group, the cell viability of the Al(mal)3 high-dose group was decreased by 18% (P<0.05); compared with the Al(mal)3 high-dose group, the cell viability of the C188-9 intervention group was significantly elevated by 14% (P<0.05). Compared with the control group, the expression levels of CD68 in the Al(mal)3 low-, medium-, and high-dose groups were elevated by 19%, 20%, and 21%, respectively (P<0.05); the expression level of CD206 in the Al(mal)3 high-dose group was decreased by 25% (P<0.05). Compared with the Al(mal)3 high-dose group, the expression level of CD68 in the C188-9 intervention group was reduced by 9% (P<0.05), whereas the expression level of CD206 was elevated by 22% (P<0.05). Compared with the control group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the Al(mal)3 high-dose group increased by 129% and 127%, respectively (P<0.05). Compared with the Al(mal)3 high-dose group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the C188-9 intervention group were decreased by 55% and 54%, respectively (P>0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)3 high-dose group (P<0.05), the expression levels of cleaved-casepase-1 protein increased by 28% and 35% in the Al(mal)3 medium- and high-dose groups (P<0.05), and the expression levels of ASC increased by 22%, 25%, and 53% in the Al(mal)3 low-, medium- and high-dose groups (P<0.05), respectively. Compared with the Al(mal)3 high-dose group, the expression levels of NLRP3, cleaved-casepase-1, and ASC proteins in the C188-9 intervention group decreased by 30%, 19%, and 32%, respectively (P<0.05). Compared with the control group, the levels of IL-1β in the Al(mal)3 medium- and high-dose groups increased by 18% and 21%, respectively (P<0.05), and the level of IL-18 in the Al(mal)3 high-dose group increased by 10% (P<0.05). Compared with the Al(mal)3 high-dose group, the IL-18 levels were reduced by 23% in the C188-9 intervention group (P<0.05). The content of anti-inflammatory factor IL-10 did not differ significantly between groups (P>0.05). Conclusion Aluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.

Effect of GSK-3β-mediated DRP1 on inhibition of primary hippocampal neuronal growth induced by aluminum / 环境与职业医学

Background Aluminum (Al) can cause irreversible damage to neurons and synapses function, and the mechanism may be connected to mitochondrial damage caused by glycogen synthase kinase-3β (GSK-3β) regulating dynamin-related protein 1 (DRP1), resulting in inhibition of the growth of neuronal protrusions. Objective To investigate the role of GSK-3β regulating DRP1 in the inhibition of primary hippocampal neurite growth induced by Al. Methods Neurons were extracted from the hippocampus of newborn mice (≤24 h old) for primary culture. On day 6, the purity of neurons was detected by immunofluorescence. On day 10, neurons with good growth state were selected for Al exposure and GSK-3β inhibitor SB216763 (SB) intervention. The experiment design included a blank control group, a dimethyl sulfoxide (DMSO) group, an Al (20 μmol·L−1) group, a SB (1 μmol·L−1) group, and a SB (1 μmol·L−1) + Al (20 μmol·L−1) group. After primary hippocampal neurons were treated with Al or SB for 48 h, cell viability was detected by CCK-8 assay, the mitochondrial morphology of primary hippocampal neurons was observed by transmission electron microscopy, the total protrusion length of primary hippocampal neurons was scanned and analyzed by laser confocal imaging, and their complexity was analyzed by Sholl analysis. The expression levels of phospho-GSK-3β, GSK-3β, and DRP1 were detected by Western blotting. Results The immunofluorescent results showed that the purity of primary neurons was higher than 90%. After the Al exposure and the SB intervention for 48 h, compared with the blank control group, there was no obvious difference in cell viability in the DMSO group and the SB group (P>0.05), and the Al group showed reduced cell viability (P=0.006); there was no obvious difference in cell viability between the SB+Al group and the Al group (P>0.05). Compared with the blank control group, there was no obvious difference in the average total length of protrusion in the DMSO group and the SB group (P>0.05), and the Al group showed reduced average total length of neurite (P<0.001); the average total neurite length in the SB+Al group was significantly increased compared with that in the Al group (P=0.001). The results of Sholl analysis revealed that, within 130 μm from the cytosol, the number of intersections of neurons in each group increased with the increase of distance. Above 130 μm from the cytosol, the number of intersections of neurons in each group decreased gradually with increase of distance. At 130 μm and 310 μm from the cytosol, compared with the blank control group, the number of neuronal intersections in the DMSO group and the SB group had no obvious difference (P>0.05), and that in the Al group was significantly reduced (P<0.05); there was no obvious difference in the number of neuronal intersections between the SB+Al group and the Al group (P>0.05). The mitochondrial structure of the blank control group was complete and the crest was clearly visible; there was no apparent variation in the mitochondrial structure in the DMSO group and the SB group; the mitochondria in the Al group were vacuolated and the crista disappeared; the SB+Al group showed clearer crista than the Al group. The difference in GSK-3β phosphorylation level among groups was statistically significant (F=45.841, P<0.001). Compared with the blank control group, the GSK-3β phosphorylation level showed not significantly different in the DMSO group (P>0.05), increased in the SB group (P=0.022), and significantly reduced in the Al group (P<0.001); the GSK-3β phosphorylation level was significantly higher in the SB+Al group than in the Al group (P<0.001). The difference in DRP1 protein level among groups was statistically significant (F=8.389, P=0.003). Compared with the blank control group, the DRP1 protein levels in the DMSO group and the SB group were not significantly different (P>0.05), and significantly increased in the Al group (P=0.001); the DRP1 protein level in the SB+Al group was significantly lower than that in the Al group (P=0.029). Conclusion Al may increase the level of DRP1 protein by activating GSK-3β, causing mitochondrial damage and inhibiting neuronal protrusions growth.

Effects of occupational aluminum exposure, types of alcohol consumption, and their interaction on cognitive function of workers / 环境与职业医学

Background Occupational aluminum exposure is closely related to cognitive impairment, and alcohol consumption is also closely related to cognitive dysfunction. Objective To explore the effects of types of alcohol consumption on cognitive function of occupational aluminum exposed workers. Methods A total of 181 workers aged from 23 to 56 years were selected by cluster sampling method in an electrolytic aluminum workshop of an aluminum plant in a region and in a maintenance workshop of another plant in the same region from July to August, 2019. Venous blood was collected, and plasma aluminum concentration was determined by inductively coupled plasma mass spectrometry. The study subjects were divided into low and high exposure groups based on the median blood aluminum level and type of work. Their basic information was collected by occupational health examination. Workers' cognitive function was assessed using the Montreal Cognitive Assessment Scale-Beijing Edition. Logistic regression was used to analyze the association between plasma aluminum concentration and cognitive impairment, and between the types of alcohol consumption (including Baijiu, red wine, and beer) and cognitive impairment, Unconditional logistic regression was used to fit multiplicative interaction model as well as additive interaction model of plasma aluminum concentration and the types of alcohol consumption, and to calculate the relative excess relative risk due to interaction (RERI) and attributable proportion due to interaction (AP). Results The M (P25, P75) concentrations of plasma aluminum were 40.01 (25.05, 60.56) µg·L−1 in the total study subjects, 25.16 (17.13, 34.78) µg·L−1 in the low exposure group and 60.56 (47.40, 68.53) µg·L−1 in the high exposure group. After adjusting the type of alcohol consumption, drinking, age, duration of exposure to aluminum, education, marital status, and smoking, the odds ratios for impairments of attention, language expression, and overall cognitive function in the high exposure group were 4.295 (95%CI: 1.912-9.648), 5.687 (95%CI: 1.355-23.867), and 2.720 (95%CI: 1.225-6.040) times of the low exposure group respectively. Besides, after adjusting blood aluminum concentration, total alcohol consumption, age, duration of exposure to aluminum, education, marital status, and smoking, the risk of attention impairment of the Baijiu drinkers was 2.613 (95%CI: 1.054 to 6.837) times of the non-Baijiu drinkers; the risks of impairment of visuospatial abilities and execution functions, language expression, delayed recall, and overall cognitive function of the beer drinkers were 3.165 (95%CI: 1.285-7.797), 17.898 (95%CI: 1.590-201.480), 3.118 (95%CI: 1.215-8.003), and 3.824 (95%CI: 1.736-8.423) times of the non-beer drinkers. There were both additive [RERI (95%CI): 1.745 (1.394-2.097), AP (95%CI): 0.415 (0.201-0.630)] and multiplicative (OR=3.591, 95%CI: 1.393-9.255) interactions between Baijiu intake and plasma aluminum concentration levels on the attention domain. The cognitive impairment attributed to the interactive effects of drinking Baijiu and plasma aluminum concentration in individuals with attention impairment accounted for 41.5%. There were both additive [RERI (95%CI): 5.955 (0.562-11.328), AP (95%CI): 0.829 (0.577-1.081)] and multiplicative (OR=42.174, 95%CI: 5.469-325.252) interactions between beer drinking and plasma aluminum concentration on the overall cognitive function. Among the individuals with overall cognitive impairment, the cognitive impairment caused by the interaction of beer drinking and plasma aluminum concentration accounted for 82.9%. Conclusion Occupation aluminum exposed workers' attention, language expression, and overall cognitive function are closely related to their plasma aluminum concentration. Plasma aluminum concentrations have interactions with Baijiu and beer consumption on cognitive impairment of workers.

Role and mechanism of miRNA-29a/PTEN pathway in neuronal network damage caused by aluminum / 环境与职业医学

Background Aluminum can cause synaptic plasticity damage in the hippocampus, probably due to blocked interneuronal signal transmission. MicroRNA-29a (miR-29a) can target phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression and participate in the generation of neuronal networks, and may be involved in the effect of aluminum on the electrical activity of neuronal networks. Objective To study the role and mechanism of miR-29a-targeted PTEN in aluminum-induced neuronal network injury in primary hippocampal neurons of ICR mice treated with maltol aluminum [Al(mal)3] in vitro. Methods Primary hippocampal neurons of ICR mice born within 24 h were cultured in vitro. The purity of neurons was determined by labeling neuron-specific microtubule-associated protein 2 (MAP2) by immunofluorescence staining on day six of the culture; neurons were treated with different concentrations of Al(mal)3, and divided into a control group, and 10, 20, and 40 μmol·L−1 Al(mal)3 groups, and neuronal cell viability was detected by CCK-8 method. Al(mal)3 at 20 μmol·L−1 was selected for subsequent experiments to establish a neuronal network injury model for intervention. The lentivirus infection method was used to transfect miR-29a into neurons, which were divided into mNG, mNG+20 μmol·L−1 Al(mal)3, miR-29a, and miR-29a+20 μmol·L−1 Al(mal)3 groups, and micro-electrode array (MEA) was used to analyze the firing of neuronal network. The expressions of miR-29a and PTEN mRNA in each group were detected by real-time PCR (RT-PCR), and the expression of PTEN protein in each group was detected by Western blotting. Results The purity of primary mouse hippocampal neurons was greater than 90%, and the viability of the neurons was above 80% in all groups. At 48 h of the designed Al(mal)3 treatments, the changes in spike frequency, burst frequency, network burst frequency, and synchrony index of neurons cultivated on MEA plates in the control group were 207.56%±38.70%, 73.19%±46.43%, 75.42%±33.04%, and 117.13%±15.54%, respectively; the Al(mal)3 groups’ neuronal network electrical activity showed a decreasing trend. Compared with the control group, the spike frequency, burst frequency, network burst frequency, and synchrony index of the 20 and 40 μmol·L−1 Al(mal)3 groups significantly decreased (The changes were 171.70%±28.08%, 49.20%±23.23%, 50.20%±18.18%, and 85.45%±20.30%; 150.68%±26.15%, 43.43%±15.54%, 52.05%±26.31%, and 26.80%±8.29%, respectively, P < 0.05). Compared with the control group (1.00), the miR-29a relative expression levels were significantly decreased in the 20 μmol·L−1 Al(mal)3 group (0.74±0.09) and the 40 μmol·L−1 Al(mal)3 group (0.62±0.12) (P < 0.05); the relative expression levels of PTEN mRNA were significantly increased in the 20 μmol·L−1 Al(mal)3 group (1.32±0.12) and the 40 μmol·L−1 Al(mal)3 group (1.48±0.11) (P < 0.05); the PTEN protein relative expression levels (1.29±0.12 and 1.82±0.10, respectively) were also significantly increased (P < 0.05). By overexpressing miR-29a in mouse primary hippocampal neurons, the spike frequency, burst frequency, and network burst frequency were significantly higher in the miR-29a group compared with the mNG group (The changes were 252.80%±62.03%, 171.65%±56.30%, and 197.75%±27.12%, respectively, P<0.05). The mNG+20 μmol·L−1 Al(mal)3 group showed a significant decrease in all indicators of neuronal network electrical activity (The changes were 123.28%±47.31%, 66.62%±31.53%, 70.60%±12.48%, and 52.86%±20.26%, respectively, P < 0.05). Compared with the mNG+20 μmol·L−1 Al(mal)3 group, the electrical activity indicators of neuronal network were significantly higher in the miR-29a+20 μmol·L−1 Al(mal)3 group (The changes were 161.41%±42.13%, 101.16%±30.63%, 127.02%±29.58%, and 109.73%±15.61%, respectively, P < 0.05). Compared with the mNG group (1.00), the neuronal PTEN mRNA relative expression (0.67±0.11) and the PTEN protein expression (0.75±0.08) were decreased in the miR-29a group (P < 0.05); the PTEN mRNA relative expression (1.32±0.12) and the PTEN protein relative expression (1.46±0.15) in the mNG+20 μmol·L−1 Al(mal)3 group were increased (P < 0.05). Compared with the mNG+20 μmol·L−1 Al(mal)3 group, the PTEN mRNA relative expression (0.93±0.06) and the PTEN protein relative expression (0.92±0.09) were decreased in the miR-29a+20 μmol·L−1 Al(mal)3 group (P < 0.05). Conclusion Aluminum significantly inhibits the electrical activity of hippocampal neuronal networks, and miRNA-29a may be involved in the aluminum-induced impairment of hippocampal neuronal network electrical activity by regulating PTEN expression.

Spinal Angiolipomas : Clinical Characteristics, Surgical Strategies and Prognosis

Objective@#: Angiolipomas are usually found in the subcutaneous tissue of the trunk and limbs. Spinal angiolipomas (SALs) are uncommon and have rarely been reported. We report a series of nine SALs patients who received surgical treatment in our department. To summarize the clinical characteristics of SALs, propose our surgical strategies, and evaluate the effects of the operation. @*Methods@#: This was a retrospective review of nine SALs patients who received surgical treatment from August 2015 to March 2020. Total or subtotal resection was determined by the axial localization (dorsal or ventral) and the extent of intervertebral foramen involvement. The outcomes were assessed based on the modified Japanese Orthopaedic Association (mJOA) scoring system utilized before surgery and at various follow-up points. @*Results@#: Among the nine patients, the mean mJOA score before surgery was 6.6±2.3, compared with 10.1±1.1 at the last follow-up time point (33.4±11.8 months). All patients achieved good outcomes, even in cases of subtotal resection. @*Conclusion@#: Early surgical resection of SALs is recommended, and the specific procedures should be determined by the axial localization (dorsal or ventral) and the extent of intervertebral foramen involvement. Most of the patients had a good prognosis, even in cases of subtotal resection.

Effectiveness of early intervention with levothyroxine sodium in pregnancy complicated with hypothyroidism / 中华内分泌外科杂志

Objective:To investigate the effectiveness of early levothyroxine intervention in pregnancy complicated with hypothyroidism.Methods:A retrospective analysis was performed on 132 pregnant patients with hypothyroidism admitted to the Department of Endocrinology, Anyang People’s Hospital from Nov. 2018 to Sep. 2021. Among them, 68 cases with levothyroxine sodium early intervention were included in the intervention group, and 64 cases without intervention were included in the non-intervention group. The differences in vascular endothelial function indexes, thyroid function indexes, and blood lipid indexes before and after treatment in the intervention group were compared with those in the non-intervention group. The incidence of obstetric complications such as preeclampsia, fetal growth restriction, and adverse pregnancy outcomes of abortion and neonatal asphyxia were compared between the two groups. SPSS 21.0 software was used to process data, measurement data were subjected to t test, and enumeration data were subjected to χ 2 test. Results:After treatment, the endothelium-dependent brachial artery blood flow-mediated vasodilation index (FMD) index, nitric oxide (NO) , and endothelin-1 (ET-1) levels in the intervention group were significantly better than those in the non-intervention group [ (10.37%) ±1.54%) vs (7.25% ± 1.09%) , (60.85 ± 7.03) umol/L vs (39.11 ± 4.31) umol/L, (112.96 ± 13.58) umol/L vs (238.85 ± 26.05) umol/L]. After treatment, the serum thyroid stimulating hormone (TSH) in the intervention group was significantly lower than that in the non-intervention group [ (2.25±0.26) mU/L vs (8.79±1.60) mU/L] ( P<0.001) . After treatment, the levels of total cholesterol (TC) , triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) in the intervention group were significantly lower than those in the non-intervention group [ (3.52±0.91) mmol/L vs (6.51±1.31) mmol/L L, (1.30±0.31) mmol/L vs (1.44±0.36) mmol/L, (2.29±0.31) mmol/L vs (3.32±0.44) mmol/L] ( P<0.001, P=0.036, P<0.001) . The incidence of obstetric complications such as preeclampsia, fetal growth restriction, premature rupture of membranes, and abnormal amniotic fluid volume in the intervention group were significantly lower than those in the non-intervention group (5.88% vs 17.19%, 1.47% vs 9.38%, 10.29% vs. 23.44%, 2.94% vs 12.50%) ( P=0.041, 0.043, 0.043, 0.038) ; the incidence of miscarriage, premature birth, neonatal asphyxia, cesarean section and other adverse pregnancy outcomes in the intervention group were significantly lower than those in the non-intervention group (1.47% vs 9.38%, 4.69% vs 15.36%, 2.94% vs 10.94%, 57.35% vs 75.00%) ( P=0.043, 0.031, 0.038, 0.033) . Conclusion:Early intervention with levothyroxine in pregnancy complicated with hypothyroidism is beneficial to improve thyroid function, reduce blood lipid level, protect vascular endothelial function, reduce related obstetric complications, and reduce the incidence of adverse pregnancy outcomes for mothers and infants.

Effect of aluminum-maltolate on primary hippocampal neuron neurite damage by regulating CRMP2 through GSK-3β in mice / 环境与职业医学

Background Aluminum can induce irreversible structural and synaptic functional damage, and the associated mechanism may be related to the neurite damage regulated by glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP2). Objective This experiment is conducted to investigate the effect of aluminum-maltolate [Al(mal)3] on primary hippocampal neuron neurites in mice, and reveal the role of GSK-3β-CRMP2 in this process. Methods The hippocampus of newborn ICR mice (≤ 24 h old) was used for primary neuronal cultures. On the 5th day in vitro (DIV5), neuron purity detection were performed by confocal laser scanning microscopy. On DIV7, the neurons were transfected with lentiviral vector-mediated mNeonGreen. On DIV10, the neurons with mNeonGreen fluorescence in good growth state were treated with Al(mal)3. The stage I experimental groups were blank control group, maltol group, 10 µmol·L−1 Al group, 20 µmol·L−1 Al group, and 40 µmol·L−1 Al group. Then 20 µmol·L−1 Al was used to establish a model of neurite injury and for the intervention. The stage II experimental groups were blank control group, dimethyl sulfoxide (DMSO) group, Al (20 µmol·L−1) group, SB (GSK-3β inhibitor, 1 µmol·L−1), and SB (1 µmol·L−1)+Al (20 µmol·L−1) group. CCK-8 method was used to detect the viability of neurons. The primary hippocampal neurons of mice were scanned with high content analysis system at 0 h and 48 h after Al or SB treatment, and the density and length of neurites were analyzed. Western blotting was used to detect the expression and phosphorylation levels of CRMP2 and GSK-3β in primary hippocampal neurons of mice. Results The immunofluorescence results showed that the purity of primary neurons was more than 90%. Compared with the blank control group in stage I, the cell viability rates of the 10, 20, and 40 µmol·L−1 Al groups were decreased after 48h of Al(mal)3 treatment (P<0.05), while the cell viability rate of the maltol group had no significant change. There was no significant difference in cell viability rate among the DMSO group, the SB group, and the control group after 48h of SB treatment, and the viability rate of neurons in the SB+Al group was higher than that in the Al group (P<0.05) in stage II. The 48 h/0 h ratios of average number and length of neurites in the control group were 90.13%±11.70% and 113.24%±8.34%, respectively. The 48 h/0 h ratios in the Al group were 56.47%±16.36% and 62.06%±6.75%, respectively, which were lower than those in the control group (P<0.05). The 48 h/0 h ratios of average number of neurites in the SB group (99.03%±21.83%) was not significantly different from that in the control group, but the 48 h/0 h ratio of average length of neurites in the SB group (128.72%±15.39%) was higher than that in the control group (P<0.05). The 48 h/0 h ratios of average number (72.59%±10.89%) and length of neurites (93.84%±14.65%) in the SB+Al group were significantly increased compared with those in the Al group (P<0.05). Western blotting results showed that: There was no significant difference in GSK-3β protein level among all groups; compared with the control group (1.00±0.18), the protein level of p-GSK-3β in the Al group (0.45±0.05) was significantly decreased, and that in the SB group (1.32±0.23) was significantly increased; the protein level of p-GSK-3β in the SB+Al group (0.80±0.05) was significantly higher than that in the Al group (P<0.05). Compared with the control group (1.00±0.07), the CRMP2 protein level in the Al group (0.66±0.11) was significantly decreased (P<0.05), while that in the SB group (1.01±0.02) was not significantly changed. Compared with the control group (1.00±0.13), the p-CRMP2 protein level in the Al group (1.50±2.18) was significantly increased, and that in the SB group (0.62±0.09) was significantly decreased (P<0.05); the protein level of p-CRMP2 in the SB+Al group (1.28±0.24) was lower than that in the Al group (P<0.05). Conclusion Aluminum may activate GSK-3β, increase CRMP2 phosphorylation level, and damage neurite growth.

Analysis on the status quo and influencing factors of physician title promotion satisfaction in public hospitals / 中华医院管理杂志

Objective:To investigate the current physician title promotion satisfaction in public hospitals, and analyze the main influence factors, for references in improving their satisfaction.Methods:June to December 2018, 2 156 in-job physicians of 39 hospitals in China were surveyed with questionnaires via the medical alliances platform, in order to learn their title promotion satisfaction. General information was subject to descriptive analysis, while the main influencing factors for their satisfaction were evaluated with univariate analysis.Results:Among the 2 156 samples, the overall satisfaction scored (3.17±0.84), at a satisfaction rate of 32.88%(709/2 156), the lowest satisfaction scoring was found in the promotion ratio(2.90±1.03). The univariate analysis results indicated that such factors as teaching titles, hospital grading and their location influenced their satisfaction on title promotion with a significant difference( P<0.05), while those with medium titles presented the lowest scoring in their satisfaction. Conclusions:As the overall satisfaction rate for their professional title promotion was not high, it is necessary to take the following measures. They refer to reasonable adjustment of the proportion ratio, dynamic coordination, and proactive exploration to establish different promotion series and launch differentiated appraisal, focusing on building a scientific and reasonable promotion criteria by levels and by categories for the purpose of enhancing teambuilding of physicians.

The international experiences of Investigator-initiated Clinical Trials and implications / 中华医学科研管理杂志

Objective:To introduce the experience of international Investigator- initiated Clinical Trials (IIT), provide suggestions for the construction of IIT management system in China. Methods:Applying the literature review research methodologies to analyze the document materials, five aspects including the funding source, technical support, personnel training, management mechanism and policy assurance were analyzed.Comparison was conducted to identify possible problems existed in Chinese IIT, and further explore possible lessons that we can learn in Chinese context.Results:Identified problems of Chinese IIT include insufficient funds, unsound scientific research design, imperfect data information system, lack of standard training for researchers, as well as the urgent need for more optimized whole-process management, quality control, and policy support.Conclusions:Suggested series of measurements that including expand the funding sources, improve the construction of scientific steering committee, improve the construction of data information platform at the national level, standardize the training of researchers, and update the operation mechanism and also the regulatory requirement are proposed to enhance the IIT research quality, as well as the IIT management.

The evaluation of scientific research efficiency in a tertiary hospital based on Data Envelopment Analysis and Malmquist index / 中华医学科研管理杂志

Objective:To evaluate the scientific research efficiency and its change in a tertiary hospital, provide recommendations for improvement based on evaluation findings.Methods:We evaluated the scientific research efficiency of 35 disciplines in a tertiary hospital from 2015 to 2017 with BCC model of Data Envelopment Analysis and Malmquist index.Results:The number of DEA valid disciplines was 10, 16, 10 respectively. The average efficiency value from 2015 to 2017 of internal medicine, surgery department and supportive department was 0.62, 0.71, 0.74. The Total Factor Productivity of 2017, compared with 2015, was 1.30, which was mainly attributed to increase of Pure Technical Efficiency. There were 23 disciplines which efficiency increased and 12 disciplines which efficiency decreased.Conclusions:The scientific research efficiency of the tertiary hospital showed a rising trend. The efficiency of disciplines varied largely. For disciplines of DEA invalid or with downward trend, it is important to improve efficiency by improving management, cultivating talents, improving technology and increasing scientific output, and so on.

Network public opinion on national blood safety in 2019 / 中国输血杂志

【Objective】 To analyze the network public opinion on national blood safety in 2019, so as to effectively deal with and prevent the risk of it and create a favorable climate for voluntary blood donation. 【Methods】 Keywords such as blood donation policy, blood supply and blood transfusion risk were set up in TRS OM 5.0, and the network public opinion on national blood safety in 2019 was collected. The trend of network public opinion, regional distribution and key public opinion events were analyzed. 【Results】 A total of 2 299 581 pieces of public opinion information were collected in 2019. The trend was seasonal. The information was relatively intensive in February, April, June and December, during which hot events happened frequently. The information mainly concentrated in Beijing, Shanghai, Jiangsu, Shandong and Zhejiang. In terms of microblog netizens’ opinion. 57.1% tended to support, and 31.9% showed no support. The top 10 network public opinion events on national blood safety in 2019 were selected according to the heat value, among which 8 were positive and 2 were negative. 【Conclusion】 Network public opinion on blood safety in 2019 was mainly positive. The most intensive public opinion mainly concentrated in Beijing, Shanghai, Tianjin, Hainan, Qinghai, and Chongqing. However, as a province with a large number of ethnic minorities, Qinghai, ranked among the top 5 in China in terms of the network public opinion on blood safety per thousand, which deserved special attention and further analysis.

Recentdevelopment and enlightenment ofblood service in Japan / 中国输血杂志

From December 3rd to 7th, 2018, Institute of Blood Transfusion, Chinese Academy of Medical Sciencessenta delegation to Japantovisit 6 bloodservice institutions, including the Blood Business Service Headquarters of Japanese Red Cross Society, to learnin-deptthe recentdevelopment of blood serviceindustryin Japan.Somepractices and experience in Japanmayshed lightson the boost of domestic blood services.

Overexpression of p21 Has Inhibitory Effect on Human Hematopoiesis by Blocking Generation of CD43＋ Cells via Cell-Cycle Regulation

Background and Objectives@#p21, an important member of the Cip/Kip family, is involved in inhibitory effects of RUNX1b overexpression during the early stage of human hematopoiesis. @*Methods@#and Results: We established a human embryonic stem cell (hESC) line with inducible expression of p21 (p21/hESCs). Overexpression of p21 did not influence either mesoderm induction or emergence of CD34＋ cells, but it significantly decreased the production of CD43＋ cells and changed the expression profile of hematopoiesis-related factors, leading to the negative effects of p21 on hematopoiesis. @*Conclusions@#In RUNX1b/hESC co-cultures when RUNX1b was induced from D0, perturbation of the cell cycle caused by upregulation of p21 probably prevented the appearance of CD43＋ cells, but not CD34＋ cells. The mechanisms via which CD34＋ cells are blocked by RUNX1b overexpression remain to be elucidated.

Analysis on the layout of China’s emergency research projects during the public health emergency of COVID-19 / 中华医学科研管理杂志

Objective@#To explore the main layout and countermeasures of Scientific research projects during the public health emergency of COVID-19.@*Methods@#Literature investigation method is applied to collect information of scientific research and emergency research projects of COVID-19 funded since January 20th by different entities including national, provincial and municipal administrative departments, public health agencies, research institutes, universities and industries.@*Results@#Along with priorities identified for the emergency response and key research agendas, the national science and technology authorities at all levels and scientific research institutions have deployed a series of new science and technology projects, as well as a number of supporting policies and measures.@*Conclusions@#In the campaign of science and technology to deal with COVID-19, the leadership of Chinese government and their coordination with local agencies facilitated quick response in both R&D investment and supporting policies. Periodical achievement is recognized so far, and with the continuous development and in-depth research, the related scientific research results will be gathered into the core force of epidemic prevention. Moreover, it will improve China's capacity to deal with health emergencies and the level of medical health innovation, and better protect the health of the people.

Analysis on the layout of China’s emergency research projects during the public health emergency of COVID-19 / 中华医学科研管理杂志

Objective:To explore the main layout and countermeasures of Scientific research projects during the public health emergency of COVID-19.Methods:Literature investigation method is applied to collect information of scientific research and emergency research projects of COVID-19 funded since January 20th by different entities including national, provincial and municipal administrative departments, public health agencies, research institutes, universities and industries.Results:Along with priorities identified for the emergency response and key research agendas, the national science and technology authorities at all levels and scientific research institutions have deployed a series of new science and technology projects, as well as a number of supporting policies and measures.Conclusions:In the campaign of science and technology to deal with COVID-19, the leadership of Chinese government and their coordination with local agencies facilitated quick response in both R&D investment and supporting policies. Periodical achievement is recognized so far, and with the continuous development and in-depth research, the related scientific research results will be gathered into the core force of epidemic prevention. Moreover, it will improve China's capacity to deal with health emergencies and the level of medical health innovation, and better protect the health of the people.

The construction of scientific research evaluation index system based on STEM for the tertiary class A general hospital / 中华医学科研管理杂志

Objective:To build a scientifically applicable scientific research evaluation system based on the Science and Technology Evaluation Metrics (STEM) of Chinese hospitals.Methods:Twenty-four experts were invited to form an expert advisory group, scientific research evaluation indicators were collected according to literature review, panel discussion and expert consultation. Use Delphi method to carry out two rounds of expert consultation, calculate the authority level and positive factor of experts, and use AHP to calculate the weight of each indicator.Results:The experts invited for consultation had a high positive coefficient and a high degree of expert authority, and finally, a scientific research evaluation index system including 3 first-level indicators, 10 second-level indicators and 24 third-level indicators was established.Conclusions:The research based on STEM has developed an evaluation system well combined quantity and quality from three dimensions, including scientific research input, scientific research output and scientific research influence. Taking into full consideration of the regulatory requirement of clinical trials and the research administration of research achievements transformation, this research established an evaluation system and management model applicable to the Tertiary class A general hospitals, provided reference value for the development of the hospital's scientific research.

The effects of repetitive high-frequency magnetic stimulation in treating post-stroke depression and their evaluation using event-related potentials / 中华物理医学与康复杂志

Objective:To investigate the value of event-related brain potentials (ERPs) for evaluating the effect of repeated high-frequency transcranial magnetic stimulation (rTMS) in treating post-stroke depression.Methods:Sixty-four depressed stroke survivors were divided at random into an observation group and a control group, each of 32. Thirty-five healthy volunteers constituted a healthy control group. All of the patients were treated with 150mg/d of venlafaxine for 6 weeks. The observation group was additionally given rTMS five times a week for 6 weeks. Before and after the treatment, both patient groups were evaluated using the Hamilton depression scale (HAMD-17) as well as the visual P300.Results:After the treatment the average HAMD-17 scores of the two patient groups had decreased significantly, but with significantly greater improvement in the observation group. The total effective rate of the observation group after treatment (87.5%) was significantly higher than the control group′s rate (62.5%). Before the treatment the latency and amplitude of Cz and Fz in both patient groups was significantly delayed and lower than in the healthy group. After the treatment the average Fz amplitude in the observation group had risen and the latency had moved forward significantly compared with the other two groups. No significant differences were observed among the control group before and after the treatment. Before the treatment the average P2 and P3 latencies of the two patient groups were significantly longer than in the healthy group, while the amplitudes were significantly lower. After the treatment the average latency of P2 and the average P3 latency and amplitude of the observation group were significantly better than before the treatment. No significant differences were observed in the healthy control group.Conclusions:High-frequency rTMS can affect post-stroke depression. The MMN and visual P300 instruments can be used for rehabilitation evaluation.

Regulatory effect of metabolic glutamate receptor 1 on maltolate aluminum-induced synaptic plasticity in rats / 中国职业医学

OBJECTIVE: To observe the effect of maltolate aluminum on synaptic plasticity in the hippocampus of rats and to explore the regulatory effect and mechanism of metabotropic glutamate receptor 1(mGluR1). METHODS: Specific pathogen free healthy adult male SD rats were randomly divided into control group, aluminum group, aluminum agonist group and aluminum antagonist group, 8 rats in each group. The rats in the control group received no treatment; the rats in aluminum group were injected with 5 μL 10 mmol/L maltolate aluminum solution into the lateral ventricle; the rats in aluminum agonists and aluminum antagonist group were injected with 3 μL 10 mmol/L maltolate aluminum solution plus 2 μL 0.1 μmol/L mGluR1 agonist or 2 μL 0.2 μmol/L mGluR1 antagonists into the lateral ventricle, respectively.Maltolate aluminum solution was injected every 2 days and continued for 10 days. After maltolate aluminum exposure, the amplitudes of long-term potentiation(LTP) in hippocampal CA1 region of rats were measured, and the relative expression levels of mRNA and protein of mGluR1, N-methyl-D-aspartate receptor(NMDAR1) and protein kinase C(PKC) in hippocampus tissue of rats were detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting. RESULTS: The amplitude of LTP in hippocampal CA1 region in aluminum group and aluminum agonist group was lower than that in the control group and the aluminum antagonist group(P<0.05). Compared with the control group, the relative expression of mGluR1 mRNA and protein in the aluminum group increased, the relative expression of PKC and NMDAR1 mRNA and protein in the aluminum group decreased(P<0.05). Compared with the aluminum group, the relative expression of mGluR1 mRNA and protein in the aluminum agonist group increased, while the NMDAR1 mRNA decreased(P<0.05); the relative expression of mGluR1 mRNA and protein in the aluminum antagonist group decreased, while the NMDAR1 mRNA and protein increased(P<0.05). Compared with the aluminum agonist group, the relative expression of mGluR1 mRNA and protein decreased, while the NMDAR1 mRNA and protein increased in the aluminum antagonist group(P<0.05). The relative expression level of PKC mRNA and protein in aluminum agonist group and aluminum antagonist group was not statistically significant(P>0.05), and there was no statistical significance in these two groups compared with control group and aluminum group(P>0.05). CONCLUSION: Maltolate aluminum exposure can inhibit synaptic plasticity by inhibiting LTP in hippocampus of rats, and the mechanism may be related to the regulation of NMDAR1 expression by mGluR1.

Preparation Technology Study on Oridonin A Oral Liposomes Based on Supercritical Fluid Solution-enhanced Dispersion / 中国药房

OBJECTIVE： To optimize the preparation technology of Oridonin A oral liposomes （ORI-LIP） by using supercritical fluidsolution-enhanced dispersion （SEDS） technology， and to investigate its advantage with routine liposome preparation technologies. METHODS： Using particle size as evaluation index， orthogonal design was employed to investigate the influence of pressure， temperature and flow rate on the preparation technology of ORI-LIP by SEDS. At the same time， thin film dispersion and reverse evaporation method were used to prepare ORI liposomes. The particle size， encapsulation efficiency， drug loading amount and stability （accelerated test for 6 months） were compared among 3 methods. Moreover， the difference in dissolution behavior in vitro of ORI crude drug and 3 kinds of liposomes was evaluated. RESULTS： The optimized preparation condition of ORI liposomes by SEDS included temperature of 50 ℃， pressure of 18 MPa， flow rate of 1 mL/min. Compared with thin film dispersion and reverse evaporation method， the liposomes prepared by the SEDS method exhibited smaller particle size [（147.4±4.8）nm]， better encapsulation efficiency （67.8％）， drug-loading amount （7.8％） and stability （particle size increased slightly， encapsulation efficiency decreased only by 4.4％）. Results of in vitro dissolution test showed that compared with crude drug， release rate of each liposome was slow and persistent， and the cumulative release rate was higher. The accumulative release rate of ORI-LIP prepared by SEDS could achieve to 67.2％， and reached to dissolution equilibrium at 24 h. CONCLUSIONS： ORI-LIP prepared by SEDS has smaller particle size， higher encapsulation efficiency， drug loading amount and stability， which can improve the in vitro release of ORI. Compared with conventional methods， SEDS technology has certain advantages.

Status of China's hospital rankings and its impact on hospital discipline construction / 中华医学科研管理杂志

Objective Through combing and analyzing the existing hospital rankings in China,comparing the similarities,differences and problems of existing rankings,to improve the hospital's understanding of the ranking work,and provide reference for hospital discipline construction and development.Methods To comprehensively review and compare the major ranking of hospitals in China,such as "China's Hospital Rankings","China's Hospitals · Competitiveness Rankings","Ranking of the Best Clinical Subjects in China","China Hospitals' Science and Technology Evaluation Metrics" and "Beijing Medical Service and Key Specialist Evaluation",and to analyze from the angle of the background,characteristics,evaluation methods,evaluation dimension and so on.Results At present,the hospital rankings have their own characteristics,each with its own focus,but there is still poor accessibility of clinical data,and the evaluation index of patients' medical experience and educational work are not perfect.Conclusions The hospital ranking list is a third-party evaluation tool to promote the construction of hospital disciplines effectively.It is recommended that all relevant organizations or departments further improve the construction of the ranking system,build big data platforms for hospital evaluation,improve the data accessibility of clinical medical quality and safety indicators,build scientific and objective dynamic evaluation systems,and carry out multi-level,multi-dimensional and continuous hospital ranking work.