Mechanism of Triclosan in the Treatment of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology / 中国医学科学院学报

Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.

Puerarin Inhibits the Proliferation,Invasion,and Migration of Non-small Cell Lung Cancer Cells through Regulating miR-490/Denticleless E3 Ubiquitin Protein Ligase / 中国医学科学院学报

Objective To explore the mechanism of puerarin inhibiting the proliferation,invasion,and migration of non-small cell lung cancer cells. Methods A549 cells were cultured and treated with different concentrations of puerarin.The inhibition rate (IR) on cell proliferation was detected by CCK-8,and qRT-PCR was performed to detect the mRNA levels of miR-490 and denticleless E3 ubiquitin protein ligase(DTL).Double luciferase reporter assay was employed to identify the targets of miR-490 and DTL based on the establishment of NC mimic group,miR-490 mimic group,NC inhibitor group,and miR-490 inhibitor group.The cells treated by 20 μmol/L puerarin were classified into six groups:DMSO,puerarin,puerarin+NC inhibitor,puerarin+miR-490 inhibitor,puerarin+miR-490 inhibitor+Si-NC,and puerarin+miR-490 inhibitor+Si-DTL.Transwell was used to detect cell migration and invasion.Western blotting was performed to detect the protein levels of epithelial-mesenchymal transition-related markers E-cadherin,N-cadherin,and Vimentin. Results With the increase in puerarin concentration,the IR gradually elevated (F=105.375,P<0.001),miR-490 expression gradually increased (F=32.919,P<0.001),and DTL expression gradually decreased (F=116.120,P<0.001).Compared with NC mimic group,miR-490 mimic group had decreased luciferase activity (t=7.762,P=0.016),raised miR-490 mRNA level (t=13.319,P<0.001),and declined DTL mRNA level (t=7.415,P=0.002).Compared with those in NC inhibitor group,miR-490 demonstrated decreased mRNA level (t=9.523,P=0.001) and DTL presented increased mRNA level (t=11.305,P<0.001) in miR-490 inhibitor group.Western blotting showed that the protein level of DTL was higher in NC mimic group (t=7.953,P=0.001) than in miR-490 mimic group and higher in miR-490 inhibitor group than in NC inhibitor group (t=10.552,P<0.001).Compared with DMSO group,puerarin group showed up-regulated mRNA level of miR-490 (t=10.255,P=0.001) while down-regulated mRNA level of DTL (t=6.682,P=0.003).Compared with those in puerarin+NC inhibitor group,the mRNA level of miR-490 declined (t=10.995,P<0.001) while that of DTL raised (t=12.478,P<0.001) in puerarin+miR-490 inhibitor group.The mRNA level of miR-490 had no significant difference between puerarin+miR-490 inhibitor+Si-NC group and puerarin+miR-490 inhibitor+Si-DTL group (t=1.081,P=0.341),and that of DTL was lower in the latter group (t=14.321,P<0.001).The protein level of DTL was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=11.423,P<0.001),and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=12.080,P<0.001).Compared with DMSO group,puerarin group showed inhibited cell proliferation (F=129.27,P<0.001).The activity of cell proliferation was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (F=75.12,P<0.001),and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (F=52.59,P<0.001).Compared with DMSO group,puerarin group had suppressed cell migration (t=8.963,P=0.001).The cell migration ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=12.117,P<0.001) and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (t=12.934,P<0.001).Puerarin group showed weakened cell invasion ability compared with DMSO group (t=4.710,P=0.009).The cell invasion ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=13.264,P<0.001) and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=13.476,P<0.001).Compared with DMSO group,puerarin group showed up-regulated protein level of E-cadherin (t=7.137,P=0.002) while down-regulated protein levels of N-cadherin (t=8.828,P=0.001) and vimentin (t=6.594,P=0.003).Compared with those in puerarin+NC inhibitor group,the protein level of E-cadherin (t=12.376,P<0.001) decreased while those of N-cadherin (t=13.436,P<0.001) and vimentin (t=11.467,P<0.001) increased in puerarin+miR-490 inhibitor group.Compared with puerarin+miR-490 inhibitor+Si-NC group,puerarin+miR-490 inhibitor+Si-DTL group up-regulated the protein level of E-cadherin (t=13.081,P<0.001) while down-regulated the protein levels of N-cadherin (t=10.835,P<0.001) and vimentin (t=11.862,P<0.001). Conclusion Puerarin could inhibit the proliferation,invasion,and migration of non-small cell lung cancer cells by up-regulating miR-490 and down-regulating DTL.

Natural radioactive level in raw coal of coal mines in some regions of China / 中国辐射卫生

Objective To understand the activity concentrations of natural radionuclides 40K, 226Ra, 232Th, and 238U in raw coal of coal mines in some regions of China, and to explore the correlation between ore with different activity concentrations and the concentration of radon and its progeny in the workplace. Methods Raw coal samples were collected in twelve coal mines in five provinces, and the activity concentrations of 40K, 226Ra, 232Th, and 238U were measured by a high-purity germanium γ-ray spectrometric system. Results The activity concentrations of four natural radionuclides in the raw coal samples of twelve coal mines were all lower than 1000 Bq/kg, and the activity concentration of 238U in one coal mine was close to 100 Bq/kg. The content of 40K, 226Ra, 232Th, and 238U in different coal mines varied greatly, but 226Ra, 232Th, and 238U were basically at the same level in the same coal mine. Conclusion None of the 12 coal mines belong to radio active mines. One of the coal mines investigated has the activity concentrations of 226Ra, 232Th, and 238U close to the standard limit for restricted-use management mines. It is suggested to study the correlation between the content of 226Ra in raw ore, intermediate products, tailings(slag), or other residues and the concentration of radon and its progeny in mines. Monitoring and protection of radon and its progeny in the decay chain should be strengthened for coal mines with high activity concentrations of natural radionuclides 226Ra, 232Th, and 238U.

Dosiomics-based prediction of incidence of radiation pneumonitis in lung cancer patients / 中华放射肿瘤学杂志

Objective:To explore the potential of dosiomics in predicting the incidence of radiation pneumonitis by extracting dosiomic features of definitive radiotherapy for lung cancer, and building a machine learning model.Methods:The clinical data, dose files of radiotherapy, planning CT and follow-up CT of 314 patients with lung cancer undergoing definitive radiotherapy were collected retrospectively. According to the clinical data and follow-up CT, the radiation pneumonia was graded, and the dosiomic features of the whole lung were extracted to establish a machine learning model. Dosiomic features associated with radiation pneumonia by LASSO-LR with 1000 bootstrap and AIC backward method with 1000 bootstraps were selected. Training cohort and validation cohort were randomly divided on the basis of 7:3.Logistic regression was used to establish the prediction model, and ROC curve and calibration curve were adopted to evaluate the performance of the model.Results:A total of 120 dosiomic features were extracted. After LASSO-LR dimensionality reduction, 12 features were selected into the "feature pool".After AIC, 6 dosiomic features were finally selected for model construction. The AUC of training cohort was 0.77(95% CI: 0.65 to 0.87), and the AUC of validation cohort was 0.72 (95% CI: 0.64 to 0.81). Conclusion:The dosiomics prediction model has the potential to predict the incidence of radiation pneumonia, but it still needs to include multicenter data and prospective data.

Study on the effects of the changes in respiratory status on gated stereotactic radiotherapy using an in-house developed motion phantom / 中华放射医学与防护杂志

Objective:To evaluate the effects of the changes in respiratory status on gated stereotactic radiotherapy under free breathing guided by real-time position management (RPM).Methods:This study simulated the baseline shift, change in respiratory rate, end-expiratory delay, end-inspiratory delay, and irregular breathing using an in-house developed motion phantom. Moreover, this study analyzed the correlation between the changes in the above states of three plans, three-dimensional conformal radiotherapy(3D-CRT), intensity modulated radiotherapy(IMRT), and volumetric modulated arc therapy(VMAT) and the position of the ball at the center of the motion phantom (L) and the exposed dose of the phantom in the ionization chamber (the dose).Results:The in-house developed phantom presented high setup repeatability and measurement stability. There was a positive correlation between L and the baseline shift ( r = 0.99, P < 0.01). The change in the dose was less than 4% when the baseline shift was less than the setup error, while the dose declined rapidly and was negatively correlated with the baseline shift otherwise ( r= -0.95, P < 0.01). Moreover, there was statistically significant difference in dose when the baseline shift exceeded the setup error or not ( Z = -3.06, P < 0.01). There was no significant difference in the rate of the dose affected by baseline shift in the three plans ( P > 0.05). The changes in respiratory rate had little effect on L and the dose. Both end-inspiratory delay and end-expiratory delay reduced the planned dose of the three plans, with a maximum decrease of up to -1.74%. Furthermore, the end-inspiratory delay has greater effects on the planned dose than the end-expiratory delay( Z = -2.67, P< 0.01). However, there was no significant correlation between the dose and the delay duration ( P > 0.05), and no significant difference in the rate of the planned dose of the three plans affected by respiratory waveform change ( P > 0.05). Irregular breathing had greater effects on the dose. Specifically, the dose from six repeated measurements of 3D-CR, IMRT, VMAT was (709.68±180.00), (751.40±127.16), and (750.00±185.60) cGy, respectively, all less than the prescribed dose with a poor consistency. Conclusions:The changes in the patients′ respiratory status will reduce the dose, especially when the baseline shift exceeds the setup error threshold or large respiratory waveform variation corresponding to irregular breathing occurs. Moreover, there is no correlation between the decrease in the dose and the radiotherapy technology.

Estrogen Receptor-A in Medial Preoptic Area Contributes to Sex Difference of Mice in Response to Sevoflurane Anesthesia / 神经科学通报·英文版

A growing number of studies have identified sex differences in response to general anesthesia; however, the underlying neural mechanisms are unclear. The medial preoptic area (MPA), an important sexually dimorphic structure and a critical hub for regulating consciousness transition, is enriched with estrogen receptor alpha (ERα), particularly in neuronal clusters that participate in regulating sleep. We found that male mice were more sensitive to sevoflurane. Pharmacological inhibition of ERα in the MPA abolished the sex differences in sevoflurane anesthesia, in particular by extending the induction time and facilitating emergence in males but not in females. Suppression of ERα in vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females. Furthermore, ERα knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia. Collectively, MPA ERα positively regulates the activity of MPA GABAergic neurons in males but not in females, which contributes to the sex difference of mice in sevoflurane anesthesia.

Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC), and to explore the mechanism of action of these medicines.@*METHODS@#In this retrospective, singlecenter study, prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines.@*RESULTS@#Taking CM more than 6 months was significantly associated with improved survival outcomes. In total, 77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (P<0.05). A total of 1,036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease, including fluid shear stress, interleukin-17 signaling, signaling between advanced glycan end products and their receptors, cellular senescence, tumor necrosis factor signaling, p53 signaling, cell cycle signaling, steroid hormone biosynthesis, T-helper 17 cell differentiation, and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6.@*CONCLUSIONS@#Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself.

Effects of bisphenols on proliferation and oxidative stress of BRL 3A rat liver cells and their mutagenicities / 预防医学

Objective@#To examine the effects of bisphenol A (BPA), bisphenol S ( BPS ), bisphenol F ( BPF ) and bisphenol AF ( BPAF ) on the proliferation and oxidative stress of BRL 3A rat liver cells, and to preliminarily evaluate their mutagenicities.@*Methods@#In vitro cultured BRL 3A rat liver cells were treated with BPA, BPS, BPF and BPAF at concentrations of 0, 5, 10, 25, 50, 100, 150 and 200 μmol/L for 48 h, respectively. Then, the cell viability was determined using the CCK-8 assay, and the half maximal inhibitory concentration ( IC50 ) was calculated. The minimum inhibitory concentration for BRL 3A cell proliferation was screened, and the intracellular reactive oxygen species ( ROS ) was measured in BRL 3A cells using the 2',7'-dichlorodihydrofluorescein diacetate ( DCFH-DA ) assay. In addition, the effects of BPA, BPS, BPF and BPAF at concentrations of 1 000, 200, 40, 8 and 1.6 μg/plate on the mutant colonies of histidine-deficient Salmonella typhimurium ( TA1535, TA97a, TA98, TA100 and TA102 ) were tested using the Ames test.@*Results@#Treatment with BPA and BPF at concentrations of 100 to 200 μmol/L and with BPAF at concentrations of 25 to 200 μmol/L inhibited BRL 3A cell survival at a concentration-dependent manner, while exposure to BPS at concentrations of 5 to 200 μmol/L resulted in no changes in BRL 3A cell survival. The IC50 values of BPA, BPS, BPF and BPAF were 131.7, >200, 187.5 and 21.6 μmol/L against BRL 3A cells, respectively. Treatment with BPS at 100 μmol/L or BPAF at 25 μmol/L caused no significant changes in the ROS level; however, exposure to BPA at 100 μmol/L and BPF at 100 μmol/L significantly increased the ROS level. Ames test showed that BPA, BPS, BPF and BPAF did not induce mutagenicity in TA1535, TA97a, TA98, TA100 or TA102 strains.@*Conclusions@#BPAF shows the highest cytotoxicity to BRL 3A cells, and low-concentration exposure to BPS has few effects on BRL 3A cells. The cytotoxicity of bisphenols against BRL 3A cells may be associated with the induction of oxidative stress. None of the four bisphenols show mutagenic effects under the present experimental conditions.

Objectives of screening for depression in adolescents / 中国学校卫生

Abstract@#Depression is a major public health issue among adolescents. The Ministry of Education of China recently proposed to integrate depression screening into students school health check among adolescents. However, there are inconsistencies regarding the strength of recommendation and implementation details of routine screening for adolescent depression across professional organizations and countries. This paper outlines the epidemiology and risk factors of adolescent depression and summarizes relevant international guidelines and recommendations. We suggest that before the national implementation of school based depression screening, key issues including scientific evidence, execution details, resource allocation and ethical considerations need to be examined in close collaboration with all stakeholders. Systematic piloting followed by rigorous evaluation will also be needed.

Efficacy and safety of inhalation of pulmonary surfactant using vibrating mesh nebulizers combined with nasal continuous positive airway pressure in the treatment of neonatal respiratory distress syndrome / 中华危重病急救医学

Objective:To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS).Methods:A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. Results:A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO 2/FiO 2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO 2/FiO 2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO 2/FiO 2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO 2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found ( P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. Conclusion:Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO 2/FiO 2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.

Significance of serum FGF19, Klotho and FGFR4 protein expression in patients with primary biliary cirrhosis / 中国基层医药

Objective:To investigate the significance of serum fibroblast growth factor 19 (FGF19), Klotho and fibroblast growth factor receptor 4 (FGFR4) protein expression in patients with primary biliary cirrhosis (PBC).Methods:Sixty-three patients with PBC who received treatment in Ningbo Huamei Hospital, University of Chinese Academy of Sciences between August 2017 and July 2020 were included in the PBC group. An additional 51 healthy patients who concurrently received physical examination in the same hospital were included in the control group. Serum FGF19, Klotho and FGFR4 protein expression were determined by enzyme linked immunosorbent assay.Results:Serum FGF19 and FGFR4 protein in PBC group were (178.86 ± 21.28) ng/L and (2.96 ± 0.47) ng/L, respectively, which were significantly higher than those in the control group [(69.93 ± 12.12) ng/L, (1.21 ± 0.35) ng/L, t = 32.51, 27.98, both P < 0.05]. Klotho protein expression in the PBC group was significantly lower than that in the control group [(3.25 ± 0.89) μg/L vs. (9.67 ± 1.53) μg/L, t = 22.08, P < 0.05]. Serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the PBC group were (84.25 ± 13.24) U/L, (71.82 ± 10.35) U/L, (278.93 ± 32.45) U/L, respectively, which were significantly higher than those in the control group [(23.76 ± 3.42) U/L, (23.10 ± 4.53) U/L, (76.81 ± 16.36) U/L, t = 31.75, 31.26, 40.48, all P < 0.05]. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of FGF19 in the diagnosis of PBC were 76.67% and 61.90%, respectively, they were 58.82% and 66.67% for Klotho protein diagnosis, 54.55% and 76.67% for FGFR4 protein. Pearson analysis revealed that there was a positive linear relationship between FGF19 and FGFR4 protein ( r = 0.78, P < 0.05), while there was a negative linear relationship between Klotho protein and FGFR4 protein ( r = -0.72, P < 0.05). Conclusion:In patients with PBC, serum FGF19 and FGFR4 protein levels are increased, while Klotho protein level is decreased. There is a positive linear relationship between FGF19 and FGFR4 protein, and there is a negative linear relationship between Klotho protein and FGFR4 protein. This study is highly innovative and scientific.

Metabolomics-based comparative analysis of the effects of host and environment on Viscum coloratum metabolites and antioxidative activities / 药物分析学报

Viscum coloratum(Komn.)Nakai is a well-known medicinal hemiparasite widely distributed in Asia.The synthesis and accumulation of its metabolites are affected by both environmental factors and the host plants,while the latter of which is usually overlooked.The purpose of this study was to comprehensively evaluate the effects of host and habitat on the metabolites in V.coloratum through multiple chemical and biological approaches.The metabolite profile of V.coloratum harvested from three different host plants in two habitats were determined by multiple chemical methods including high-performance liquid chromatography-ultraviolet(HPLC-UV),gas chromatography-flame ionization detector(GC-FID)and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-QTOF/MS).The differences in antioxidant efficacy of V.coloratum were determined based on multiple in vitro models.The multivariate statistical analysis and data fusion strategy were applied to analyze the dif-ferences in metabolite profile and antioxidant activity of V.coloratum.Results indicated that the metabolite profile obtained by various chemical approaches was simultaneously affected by host and environment factors,and the environment plays a key role.Meanwhile,three main differential metab-olites between two environment groups were identified.The results of antioxidant assay indicated that the environment has greater effects on the biological activity of V.coloratum than the host.Therefore,we conclude that the integration of various chemical and biological approaches combined with multivariate statistical and data fusion analysis,which can determine the influences of host plant and habitat on the metabolites,is a powerful strategy to control the quality of semi-parasitic herbal medicine.

The Changes of Peripheral Blood FⅫa-AT, TSP-1, LA Ratio in Patients with Systemic Lupus Erythematosus and the Clinical Value of Combined Diagnosis of Thrombotic Events / 中国实验血液学杂志

OBJECTIVE@#To explore the changes of Ⅻ antithrombin (FⅫa-AT), thrombospondin-1 (TSP-1), and lupus anticoagulant (LA) ratio in the peripheral blood factor of patients with systemic lupus erythematosus (SLE) and the clinical value of combined diagnosis of thrombotic events.@*METHODS@#A total of 133 SLE patients treated in Xingtai People's Hospital were selected and divided into simple SLE group (105 cases) and SLE complicated with thrombosis group (28 cases) according to whether thrombotic events occurred, and 102 cases of healthy people in the same period were selected as control. The clinical data of the 3 groups, the level of peripheral blood FⅫa-AT, TSP-1, and LA ratio were compared, the relationship between each peripheral blood index and SLE disease activity index (SLEDAI) score were analyzed. The influencing factors of thrombotic events in SLE patients were analyzed, and the value of each peripheral blood index in the diagnosis of SLE complicated with thrombotic events were evaluated.@*RESULTS@#The proportion of the patients with age ≥60 year, hypertension, and smoking history in SLE complicated with thrombosis group was higher than those in simple SLE group and control group (P＜0.05). The SLEDAI score, peripheral blood FⅫa-AT, TSP-1, LA ratio levels of the patients in SLE complicated with thrombosis group were significantly higher than those in simple SLE group and control group, and the simple SLE group was significantly higher than the control group (P＜0.05). FⅫa-AT, TSP-1, LA ratio in peripheral blood of SLE patients were positively correlated with SLEDAI score (r=0.663, 0.578 and 0.625). Age, blood pressure, smoking history, peripheral blood FⅫa-AT, TSP-1, LA ratio were the important influencing factors of thrombotic events in SLE patients (P＜0.05). The AUC diagnosed by the FⅫa-AT, TSP-1, and LA ratio in peripheral blood was 0.881, the 95% CI was 0.813-0.931, the sensitivity was 82.14%, and the specificity was 91.43%, which was superior to each index alone (P＜0.05).@*CONCLUSION@#Peripheral blood FⅫa-AT, TSP-1, LA ratio level changes in SLE patients are significantly related to disease activity, and the combined diagnosis of thrombotic events is more reliable.

Phagocytosis of microglia in neurodegenerative diseases / 生理学报

With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing global health crisis. Recent studies have indicated that microglia-neuron interactions are critical for maintaining homeostasis of the central nervous system. Genome-Wide Association Studies and brain imaging studies have suggested that microglia are activated in early stage of neurodegenerative diseases. Microglia are specialized phagocytes in the brain. The discovery of a new phagocytic pathway, trogocytosis, suggests that there is a close interaction between microglia and surviving neurons. In this review, we summarize the important roles of microglia in neurodegenerative diseases, and further analyze the functions and molecular mechanisms of microglia phagocytosis and trogocytosis.

Effect of Gupi Xiaoji Decoction on Pyroptosis of HepG2.2.15 Cells Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo screen the active antitumor components of Gupi Xiaoji decoction by network pharmacology and molecular docking based on the pyroptosis mediated by cysteinyl aspartate-specific protease 1 （Caspase-1） and explore its molecular mechanism in intervening in the pyroptosis of HepG2.2.15 cells through in vitro experiments. MethodThe compounds and targets of Gupi Xiaoji decoction were screened out by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） to obtain the corresponding gene symbols. The targets of Caspase-1 were collected from GeneCards，online mendelian inheritance in man（OMIM），PharmGKB，and TTD，and the compound-gene target regulatory network was constructed by Cytoscape. The protein-protein interaction（PPI） network was established and analyzed by STRING. The mechanism of the effective components of Gupi Xiaoji decoction on Caspase-1 was predicted by gene ontology（GO） functional enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The molecular docking was verified with AutoDock Vina. The plasma medicated with Gupi Xiaoji Decoction was prepared and HepG2.2.15 cells were cultured in vitro. HepG2.2.15 cells were divided into a blank plasma group，a VX-765 group，a VX-765+medicated plasma group， and a medicated plasma group. After 48 hours of intervention with 15% medicated plasma， the expression and distribution of gasdermin D-N （GSDMD-N） on the surface of the cell membrane were detected by immunofluorescence staining. The release of lactic dehydrogenase （LDH）， interleukin（IL）-1β，and IL-18 in the cell supernatant was measured by enzyme-linked immunosorbent assay（ELISA） kits. The expression of Caspase-1 and GSDMD-N was measured by Western blot. ResultThe mitogen-activated protein kinase 14 （MAPK14），MAPK1，protein kinase B1 （Akt1）， MAPK8， V-Jun sarcoma virus oncogene homolog （JUN）， and TP53 screened by network pharmacology were the main targets. The compounds 7-hydroxy-5，8-dimethoxy-2-phenyl-chromone，wogonin，rhamnazin，moslosooflavone，isorhamnetin，7-O-methylisomucronulatol，formononetin，calycosin，luteolin，quercetin，kaempferol，β-sitosterol，and baicalein screened by network pharmacology were the main active components of Gupi Xiaoji decoction. Go enrichment analysis showed that multiple biological processes were involved， including responses to oxidative stress and metal ions，ubiquitin-like protein ligase binding，and phosphatase binding. KEGG pathway enrichment analysis showed MAPK pathway，nuclear factor（NF）-κB pathway，p53 pathway， and hypoxia-inducible factor-1（HIF-1） pathway were involved. Molecular docking showed that the targets had good binding with the components. In vitro experiments displayed that compared with the blank plasma group，the VX-765 group showed weakened GSDMD-N fluorescence signal，reduced release of LDH，IL-1β，and IL-18，and declining expression of Caspase-1 and GSDMD-N（P<0.01）， and the medicated plasma group showed increased GSDMD-N fluorescence signal， increased release of LDH，IL-1β，and IL-18，and up-regulated expression of Caspase-1 and GSDMD-N（P<0.01）. ConclusionGupi Xiaoji Decoction can induce the pyroptosis of HepG2.2.15 cells by regulating Caspase-1 through multiple targets and multiple pathways.

Serum levels of megaprolactin and gonadal hormones in patients with hyperprolactinemia induced by antipsychotics and their clinical significance / 中国基层医药

Objective:To investigate serum levels of macroprolactin and gonadal hormones in patients with hyperprolactinemia induced by antipsychotics and their clinical significance.Methods:A total of 105 female patients with schizophrenia who received treatment in Huzhou Third Municipal Hospital from June 2017 to October 2018 were included in this study. All these patients received the antipsychotic drug clozapine for 2 months. Then 50 patients with hyperprolactinemia were included in the observation group, and 55 patients who had no hyperprolactinemia were included in this control group. The scores of the Scale for the Assessment of Negative Symptoms and Scales for the Assessment of Positive Symptoms were compared between the two groups. Serum levels of macroprolactin, progesterone, testosterone, estradiol, prolactin, luteinizing hormone, and follicle-stimulating hormone were then compared between the two groups. The Spearman correlation analysis was used to analyze the correlation between serum macroprolactin level and serum progesterone, estradiol, prolactin, and luteinizing hormone levels.Results:Serum macroprolactin level in the observation group was significantly higher than that in the control group [(63.80 ± 12.13) ng/mL vs. (59.07 ± 9.84) ng/mL, t = 2.20, P = 0.030). Serum levels of progesterone, testosterone, estradiol, prolactin, luteinizing hormone, and follicle-stimulating hormone were (4.01 ± 0.47) ng/mL, (5.59 ± 1.15) ng/mL, (236.72 ± 15.14) pg/mL, (127.30 ± 12.40) ng/mL, (6.05 ± 1.10) mIU/mL, (8.52 ± 2.13) mIU/mL, respectively, and they were (10.25 ± 1.83) ng/mL, (6.01 ± 1.20) ng/mL, (433.10 ± 20.90) pg/mL, (50.58 ± 6.22) ng/mL, (7.69 ± 2.36) mIU/mL, (8.48 ± 2.01) mIU/mL, respectively in the control group. Serum levels of progesterone, estradiol, and luteinizing hormone in the observation group were significantly lower than those in the control group, and serum level of prolactin in the observation group was significantly higher than that in the control group ( t = 23.41, 54.66, 4.63, 40.61, all P < 0.05). There were no significant differences in serum levels of testosterone and follicle-stimulating hormone between the two groups ( t = 1.82, 0.09, P = 0.071, 0.921). Spearman correlation analysis results showed that serum macroprolactin level was negatively correlated with serum levels of progesterone and estradiol, and it was positively correlated with serum levels of prolactin and luteinizing hormone ( r = -0.42, -0.51, -0.68, 0.70, all P < 0.05). Conclusion:Serum levels of macroprolactin and prolactin were higher, and serum levels of progesterone, estradiol, and luteinizing hormone levels were lower in patients with hyperprolactinemia induced by antipsychotics than in patients without hyperprolactinemia. Serum levels of macroprolactin, prolactin, luteinizing hormone, progesterone, and estradiol were remarkably correlated with the balance of gonadal hormones. The study outcomes are of great innovation and science.

Inhibitory effect of vorinostat encapsulated hydroxypropyl-β-cyclodextrin eye drops on corneal neovascularization induced by alkali burns in mouse / 中华实验眼科杂志

Objective:To prepare vorinostat encapsulated hydroxypropyl-β-cyclodextrin (SAHA-CD) eye drops and investigate its inhibitory effect on corneal neovascularization (CNV) induced by alkali burns in mouse.Methods:The SAHA-CD eye drops at concentrations of 0.1%, 0.2%and 0.4%were prepared by inclusion technology with hydroxypropyl-β-cyclodextrin, and the content was assayed by high performance liquid chromatography.Seventy-five SPF mice with alkali burn-induced CNV were randomized into 0.1%SAHA-CD group, 0.2%SAHA-CD group, 0.4%SAHA-CD group, dexamethasone group and normal control group according to a random number table, 15 for each group, among which the SAHA-CD groups and dexamethasone group were treated with corresponding drugs, and model control group was treated with normal saline immediately after modeling, four times a day and five microliters each time, lasting for six days.The healing of corneal epithelium was examined with a slit lamp microscope after fluorescein sodium staining, and the areas of cornea epithelial defects were calculated using Eyestudio software.The corneal flat mount was prepared, and the length and areas of CNV were calculated with ImageJ software.The histology of mouse corneas was observed through hematoxylin and eosin staining.The expression level of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-9 (MMP-9) in cornea were measured with enzyme linked immunosorbent assay (ELISA) kits.The use and care of animals complied with the ARVO statement and this study protocol was approved by the Experimental Animal Ethics Committee of Henan Eye Institute (No.HNEECA-2020-01).Results:The actual drug contents of the 0.1%, 0.2% and 0.4%SAHA-CD eye drops were 97.62%, 98.33%and 98.14%of the labeled amount.The cornea showed edema and opacification after modeling.On the sixth day after treatment, significant differences were found in the length and areas of CNV among various groups ( F=7.655, 8.802; both at P<0.01).The areas of CNV in 0.2%SAHA-CD, 0.4%SAHA-CD and dexamethasone groups were significantly smaller than model control group, and the length of CNV in 0.1%SAHA-CD, 0.2%SAHA-CD and dexamethasone groups were significantly smaller than model control group (all at P<0.05).On the third and sixth day following modeling, significant differences in the expression levels of VEGF, bFGF and MMP-9 were found among the five groups (third day: F=6.345, 7.149, 18.650; all at P<0.01; sixth day: F=6.749, 5.105, 5.023; all at P<0.01), and the expression levels of VEGF, bFGF and MMP-9 in 0.2%SAHA-CD group were significantly lower than those in 0.1%SAHA-CD group, 0.4%SAHA-CD group and model control group (all at P<0.05). Conclusions:SAHA-CD eye drops can inhibit alkali burn-induced CNV in mouse.

Spine curvature and the cardiopulmonary exercise endurance of adolescents with idiopathic scoliosis / 中华物理医学与康复杂志

Objective:To quantify any correlation between the severity of spinal curvature of an adolescent with idiopathic scoliosis and their cardiopulmonary exercise endurance.Methods:The cardiopulmonary exercise test (CPET) results and the full-length spinal X-rays in a standing position of 64 adolescents with idiopathic scoliosis were reviewed retrospectively. Independent t-tests were used to compare the two datasets obtained from those with left or right thoracic scoliosis. The correlation between the Cobb angle and cardiopulmonary exercise endurance was analyzed using Pearson correlation coefficients, multiple factor linear regression and two-stage linear regression.Results:After adjusting for gender, age, height and weight, the multiple linear regression analysis showed that the Cobb angle was significantly negatively correlated with maximum tidal volume (β=-0.013) and significantly positively correlated with the rate of respiration (β=0.421). The relationship between the Cobb angle and cardiopulmonary exercise endurance was non-linear. With a Cobb angle > 34°, a 1° increase reduces cardiopulmonary exercise endurance by a factor of 1.4 on average. At smaller Cobb angles the corresponding increase is about 0.87 times.Conclusions:The Cobb angle is a negative predictor of ventilation during exercise among adolescents with idiopathic scoliosis. The more severe a patient′s spinal curvature, the lower the cardiopulmonary exercise endurance is likely to be.

Efficacy of esketamine for PCIA in elderly patients undergoing modified radical mastectomy for breast cancer / 中华麻醉学杂志

Objective:To evaluate the efficacy of esketamine for patient-controlled intravenous analgesia (PCIA) in elderly patients undergoing modified radical mastectomy for breast cancer.Methods:Ninety elderly female patients, aged 65-78 yr, weighing 46-75 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective modified radical surgery for breast cancer under general anesthesia, were divided into 2 groups ( n=45 each) using a random number table method: esketamine PCIA group (group E) and sufentanil PCIA group (group S). Anesthesia was induced with target-controlled infusion of propofol, intravenous atracurium besylate and sufentanil and maintained with target-controlled infusion of propofol and remifentanil and intermittent intravenous boluses of cis-benzenesulfonic acid atracurium.The patients were connected to an analgesic pump for PCIA at 10 min before completion of operation.The PCIA solution in group E contained esketamine 2 mg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCIA solution in group S contained sufentanil 1 μg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCA pump was set up with a 1.5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 1.5 ml/h, and the analgesia was performed until 48 h after operation.When numeric rating scale score ≥ 4 points and the efficacy of patient-controlled analgesia was not good, tramadol 100 mg was intravenously injected for rescue analgesia.Steward recovery scores were recorded at 4, 8, 24 and 48 h after operation.The requirement for rescue analgesia, effective pressing times of analgesic pump and time to first flatus were recorded within 48 h after operation.The nausea and vomiting, respiratory depression, dizziness and pruritus within 48 h after operation and delirium within 7 days after operation were recorded.The 40-item Quality of-Recovery scale was used to evaluate the early postoperative recovery of patients at 24 and 48 h after operation. Results:Compared with group S, the 40-item Quality of Recovery scale score was significantly increased at each time point, postoperative time to first flatus was shortened, the incidence of postoperative nausea and vomiting and pruritus was decreased ( P<0.05), and no significant change was found in the Steward recovery score at each time point after operation, effective pressing times of PCA and requirement for rescue analgesia in group E ( P>0.05). Conclusions:Esketamine provides better efficacy than sufentanil when used for PCIA in elderly patients undergoing modified radical mastectomy for breast cancer.

Effect of pertussis vaccination on clinical manifestations of infants and young children with pertussis / 中国当代儿科杂志

OBJECTIVE@#To study the effect of pertussis vaccination on the clinical manifestations of infants and young children with pertussis.@*METHODS@#A retrospective analysis was performed to investigate the differences in clinical manifestations and peripheral blood cell levels between pertussis children with different pertussis vaccination status.@*RESULTS@#A total of 1 083 children with pertussisat at age of < 3 years were enrolled, with 551 children in the unvaccinated group and 532 in the vaccinated group. Of all the children, 392 had an age of onset of < 3 months (372 were unvaccinated and 20 were vaccinated) and 691 children had an age of onset of ≥ 3 months (179 were unvaccinated and 512 were vaccinated). Compared with the vaccinated group, the unvaccinated group had a longer length of hospital stay and a higher incidence rate of respiratory failure (@*CONCLUSIONS@#Pertussis vaccination can reduce the incidence of severe pneumonia and respiratory failure and alleviate the severity of respiratory complications in infants and young children with pertussis.