Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Research progress and therapeutic perspective of iron transport balance based on "iron-inflammation" homeostatic coupling theory / 药学学报

The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.

Screening and identification of key genes ATP1B3 and ENAH in the progression of hepatocellular carcinoma: based on data mining and clinical validation / 南方医科大学学报

OBJECTIVE@#To explore the marker genes correlated with the prognosis, progression and clinical diagnosis of hepatocellular carcinoma (HCC) based on bioinformatics methods.@*METHODS@#The TCGA-LIHC, GSE84432, GSE143233 and GSE63898 datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. The differentially expressed genes (DEGs) shared by different disease types were obtained using GEO2R and edge R packages, and Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) enrichment analyses of the DEGs were performed. The expression levels of these DEGs in normal and cancerous tissues were verified in TCGA-LIHC to identify the upregulated genes in HCC. Survival analysis, receiver-operating characteristic (ROC) curve analysis, and correlation analysis between the key genes and the clinical features of the patients were carried out using the R language. The differential expressions of 15 key genes were verified in clinical samples of HCC and adjacent tissues using RT-qPCR.@*RESULTS@#A total of 118 common DEGs were obtained in the database, and among them two genes, namely ATPase Na +/K + transport subunit beta 3 (ATP1B3) and actin regulator (ENAH), showed increased expressions with disease progression. Survival analysis combined with the TCGA-LIHC dataset suggested that high expressions of ATP1B3 and ENAH were both significantly correlated with a poor prognosis of HCC patients (P < 0.05), and their AUC values were 0.821 and 0.933, respectively. A high expression of ATP1B3 was correlated with T stage, pathological stage and pathological grade of the tumors (P < 0.05), while that of ENAH was associated only with an advanced tumor grade (P < 0.05). The results of RT-qPCR showed that ATP1B3 and ENAH were both significantly upregulated in clinical HCC tissues (P < 0.05).@*CONCLUSION@#ATPIB3 and ENAH are both upregulated in HCC, and their high expressions may serve as biomarkers of progression of liver diseases and a poor prognosis of HCC.

Current drug research on intestinal mucosal healing in inflammatory bowel disease based on macrophage regulation / 药学学报

Complete healing of the intestinal mucosa is the most ideal goal in the treatment of inflammatory bowel disease (IBD). The intestinal mucosa healing not only significantly alters the course of the disease and relieves clinical symptoms, but also markedly reduces the occurrence of complications and prevents recurrence of IBD. As chronic inflammation associated with peptic ulcer damage is the main pathological feature of IBD, clinical treatment is mainly based on anti-inflammatory therapy, but such therapy cannot promote the healing of the intestinal mucosa of patients. Therefore, how to achieve long-term remission of IBD is still an urgent challenge. In the process of intestinal mucosal repair, the polarization of macrophages maintains the homeostasis of the intestinal microenvironment, which is a representative process that promotes mucosal inflammatory-repair. It is a key part of initiating tissue regeneration that should not be underestimated. In this paper, we reviewed the literature of the past decade, focusing on the promotion of intestinal mucosal healing in IBD. The discussion will highlight the importance and feasibility of regulating macrophages to promote intestinal mucosal repair. Following this thought, we discuss the shortcomings of current clinical treatments and summarize the relevant drugs which have potential to promote intestinal mucosal repair. The aim is to provide effective potential drugs and therapeutic targets for the treatment of IBD.

Effect Analysis of Artemisiae Annuae Herba and Chuanxiong Rhizoma in Treatment of Cerebral Malaria Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio^® cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （<italic>P</italic><0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of <italic>γ-</italic>interferon （IFN-<italic>γ）</italic>， interleukin-10 （IL-10）， IL-4， and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group （<italic>P</italic><0.05）， which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.

Therapeutic Efficacies of Wujiwan at Different Compatibilities in Treatment of Irritable Bowel Syndrome / 中国实验方剂学杂志

Objective:To compare the therapeutic efficacies of Wujiwan at two different compatibilities （No.1 and No.2） on irritable bowel syndrome （IBS） based on neuro-endocrine-immune network， and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine （TCM）. Method:The chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty （PTCA） in suckling rats. The animals were randomly divided into a control group， a model group， a dicetel group （0.01 g·kg^-1）， low- （0.335 g·kg^-<bold>¹</bold>）， medium- （0.67 g·kg^-<bold>¹</bold>）， and high-dose （1.34 g·kg^-<bold>¹</bold>） No. 1 Wujiwan groups， and low- （0.385 g·kg^-<bold>¹</bold>）， medium- （0.77 g·kg^-<bold>¹</bold>）， and high-dose （1.54 g·kg^-<bold>¹</bold>） No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells （MC） in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine （5-HT）， substance P （SP）， somatostatin （SS）， and vasoactive intestinal peptide （VIP） in the blood/colon tissue were detected by enzyme-linked immunosorbent assay （ELISA） and immunohistochemistry （IHC） assay. Result:There was no significant difference in body weight among different groups. Compared with the control group， the model group exhibited decreased thresholds of abdominal elevation and bow back elevation （<italic>P<</italic>0.01）， increased density of MCs in the colon tissue （<italic>P<</italic>0.05）， up-regulated levels of 5-HT， SP， and SS in the blood and colon tissue （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， and elevated VIP level in the colon tissue （<italic>P</italic><0.05）. Compared with the model group， Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation （<italic>P</italic><0.01）， diminish the count of MC in the colon tissue （<italic>P</italic><0.05）， and reduce the levels of 5-HT， SP， SS， and VIP （<italic>P</italic><0.05）. As demonstrated by the comparison of No. 1 and No. 2 Wujiwan， No. 1 was superior to No. 2 in reducing the concentrations of 5-HT， SP， and SS in the blood， especially in 5-HT （<italic>P</italic><0.01）. No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan， No. 2 significantly reduced SP expression， and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups （<italic>P</italic><0.05）. Conclusion:Wujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect， No. 1 was superior to No. 2， while in terms of local effect， No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics， while No. 2 had an advantageous effect on intestinal sensation over No. 1.

Effect and Mechanism of Shenlian Formula in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To analyze active components， its targets and signaling pathways of Shenlian formula based on network pharmacology， and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease （ASCVD）， in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine （TCMSP）， its target proteins were obtained by SymMap and ETCM Databases， and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions （PPI） network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds， 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 （PTGS2）， estrogen receptor 1 （ESR1） and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic， nitric oxide biosynthetic process， response to estradiol， angiogenesis， inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway， phosphatidylinositol-3 kinase （PI3K）/ protein kinase B （Akt） signaling pathway， hypoxia induction factor-1 （HIF-1） signaling pathway and apoptosis. Among them， the regulatory effect of Shenlian formula on apoptosis may act on not only TP53， but also different signaling pathways of apoptosis respectively， thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area， improve the myocardial histopathological changes， and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD， and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.

Investigation of Transdermal Constituents and Molecular Mechanism of Euodiae Fructus in Treatment of Diarrhea by Transdermal Drug Delivery Based on Integrated Pharmacology and UPLC-Q-TOF-MS / 中国实验方剂学杂志

Objective:To identify the transdermal constituents of Euodiae Fructus and predict its molecular mechanism in treating diarrhea by transdermal drug delivery. Method:Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and integrated pharmacology methods were used. The rapid identification of transdermal constituents of Euodiae Fructus was realized by the means of comparison of reference substances， analysis of UNIFI system and mass spectrometry. On this basis， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， SymMap， DisGeNET databases and literature were used to collected potential targets of transdermal constituents of Euodiae Fructus and targets for diarrhea-related diseases. The disease targets and drug targets were topologically analyzed to obtain the core targets， which were used for the Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Finally， Cytoscape 3.6.0 was used to build up a network of transdermal constituents-core targets-key pathways. Result:A total of 19 chemical constituents were speculatively identified from Euodiae Fructus extract， including quinolone alkaloids， limonins， indole alkaloids， organic acids and sterols. A total of 174 core targets of Euodiae Fructus for treating diarrhea were obtained by a topology analysis， signaling pathways of inflammatory response， cell proliferation， nutrient regulation and energy metabolism， signal transduction， bacterial infection were obtained through the analysis of KEGG enrichment. Conclusion:In this study， the transdermal constituents of Euodiae Fructus are identified for the first time， they can participate in the regulation of intestinal inflammation， maintain the integrity of intestinal mucosa， repaire and adjust the metabolism of the body by acting on Rac protein family， phosphatidylinositol 3-kinase， cytochrome P450 enzymes and aldo-keto reductase， respectively. In general， the molecular mechanism of Euodiae Fructus in the treatment of diarrhea is preliminarily elucidated.

Shengyutang Improves Learning and Memory Ability of Sleep Deprived Mice by Regulating Levels of Monoamine Neurotransmitters in Hippocampus / 中国实验方剂学杂志

Objective:To observe the effect of Shengyutang on the levels of monoamine neurotransmitters in the hippocampus， and explore its possible mechanism on improving the learning and memory abilities of sleep deprivation （SD） mice. Method:The 50 mice were divided into normal group， model group， estazolam group， Shengyutang low and high dose groups， with 10 mice in each group. A multi-platform water environment was used to prepare SD mouse models. The low and high-dose Shengyutang groups received intragastric administration of 12.5， 25 g·kg^-1， respectively. The mice in the model group were intragastrically administered with the same dose of normal saline daily for 8 weeks. Morris water maze experiment was used to observe the behavioral changes of SD mice in the evasion latency period， the number of crossing platforms， and the stay time in the target quadrant of each group. HE staining was used to observe the pathomorphological changes of the hippocampal tissue of each group. The expression levels of eight monoamine neurotransmitters including serotonin （5-HT），dopandne （DA），epinephrine （EP），norepinephrine （NE），5-hydroxyindole acetic acid（5-HIAA）， high vanillic acid （HVA）， levodopa（<italic>L</italic>-DOPA），and 3，4-dihydroxyphenylacetic acid（DOPAC）were detected by high performance liquid chromatography， and the expression levels of c-Fos protein in hippocampus were detected by immunohistochemistry. Result:Compared with the normal group， the SD mice in the model group were in a poorer general state and severe fatigue was observed. Compared with the model group， SD mice in each dose group of Shengyutang got improved in eating， activity， sleep， hair color， and response to external stimuli. Compared with the normal group， the body weight of SD mice in the model group was significantly reduced （<italic>P</italic><0.05）， but the body weight in the Shengyutang high-dose group increased the most as compared with the model group （<italic>P</italic><0.05）. Compared with the normal group， the hippocampal cells in the model group were disorderly arranged， incomplete in shape， increased in gap and decreased in number. Compared with the model group， the number of neurons in the hippocampus of SD mice in each dose group of Shengyutang increased. Compared with the normal group， the escape latency time of SD mice in the model group was significantly prolonged， the times of crossing platform and the residence time in the target quadrant significantly decreased （<italic>P</italic><0.01）. Compared with the model group， the times of crossing platform and the residence time in the target quadrant of mice in each dose group of Shengyutang significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the normal group， the levels of 5-HT， 5-HIAA， <italic>L</italic>-DOPA， DOPAC， EP， NE， HVA and DA in the model group significantly decreased （<italic>P</italic><0.05，<italic> P</italic><0.01）； but these levels in each dose group of Shengyutang were higher than those in model group （<italic>P</italic><0.05）. Compared with the normal group， the average MD value of c-Fos protein in the hippocampus of the model group significantly increased （<italic>P</italic><0.01）， and the expression levels of c-Fos protein in the hippocampus of Shengyutang groups were significantly lower than those in model group （<italic>P</italic><0.01）. Conclusion:Shengyutang can improve the learning and memory abilities of SD rats， and its mechanism may be related to the decrease of monoamine neurotransmitter and c-Fos protein expression.

Difference Analysis of Pharmacokinetic Behavior of Active Ingredients in Wujiwan Between Normal Rats and Rats with Irritable Bowel Syndrome / 中国实验方剂学杂志

Objective:To establish an ultra-performance liquid chromatography-mass spectrometry （UPLC-MS/MS） for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration， and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome （CVH-IBS）. Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty （PTCA） balloon stimulation method. After intragastric administration of Wujiwan （0.245 g·kg^-1）， blood was collected from the jugular vein at different time points， and the plasma concentrations of 10 active ingredients （berberine hydrochloride， palmatine hydrochloride， coptisine hydrochloride， jatrorrhizine hydrochloride， epiberberine， dihydroberberine， evodiamine， evodine， paeoniflorin， albiflorin） in Wujiwan was detected simultaneously by UPLC-MS/MS， the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated. Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group， the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent， and the peak time （<italic>t</italic>_max） was prolonged. Among them， the <italic>t</italic>_max of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute， respectively （<italic>P</italic><0.05， <italic>P</italic><0.01）. Area under the plasma concentration-time curve （AUC_0-<italic>_t</italic>） of each component increased， and evodiamine and paeoniflorin were significantly different （<italic>P</italic><0.05，<italic> P</italic><0.01）. The clearance rates （CL/<italic>F</italic>） of these 10 active ingredients were all decreased， among which berberine hydrochloride， palmatine hydrochloride and evodiamine had significant differences （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats， which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.

Shenlian extract attenuates TNF-α-induced ECV304 injury by regulating Nrf2/Keap1 signaling pathway / 中国中药杂志

This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.

Status and influencing factors of psychological violence against healthcare workers in a secondary Grade A hospital / 中国职业医学

OBJECTIVE: To study the status and influencing factors of psychological violence in healthcare workers(HCWs) of a secondary Grade A hospital. METHODS: A total of 1 028 HCWs in a secondary Grade A hospital were selected as the study subjects in 2019 using a typical sampling method. The psychological violence they had received in the previous year was investigated using the Workplace Violence in the Health Sector Country Case Studies Research Instruments--Survey Questionnaire. The results were compared with the baseline survey results in 2018. RESULTS: The incidence of psychological violence in the workplace of HCWs in 2019 was 41.6%, among which the incidence of verbal abuse, bullying/gang bullying, sexual harassment and racial discrimination were 40.2%, 9.9%, 1.9% and 1.6%, respectively. The incidence of verbal abuse, bullying/gang bullying and psychological violence among HCWs in 2019 were decreased compared with that in 2018(45.7% vs 40.2%, 12.8% vs 9.9%, 47.1% vs 41.6%, all P<0.05). The binary logistic regression analysis results showed that the HCWs in medical technology, internal medicine, surgery, outpatient and emergency departments were at higher risk of verbal abuse than that in administrative departments(all P<0.01). The HCWs in direct contact with patients had a higher risk of verbal abuse and psychological violence(all P<0.01). The HCWs aged <35 and those with night-shift-work had higher risks of bullying/gang bullying(all P<0.05). Male HCWs had a higher risk of sexual harassment than female HCWs(P<0.05). The coping style of attempting to conceal the occurrence of the incident after HCWs suffered psychological violence dropped from 5.8% in 2018 to 0.5% in 2019(P<0.01), and the proportion of no response was as high as 59.1%. CONCLUSION: The psychological violence of HCWs in this hospital is very serious and has specific features. The incidence of psychological violence decreased compared with that a year ago, but there is still room for improvement. The influencing factors of psychological violence are complex and the consequences are serious. Therefore, it is urgent for HCWs and hospital management departments to improve their management methods.

Potential therapies for COVID-19 cardiovascular complications using artemisinin and its derivatives intervene based on its cardiovascular protection / 中国中药杂志

Corona virus disease 2019(COVID-19) has brought untold human sufferings and economic tragedy worldwide. It causes acute myocardial injury and chronic damage of cardiovascular system, which has attracted much attention from researchers. For the immediate strategy for COVID-19, "drug repurposing" is a new opportunity for developing drugs to fight COVID-19. Artemisinin and its derivatives have a wide range of pharmacological activities. Recent studies have shown that artemisinin has clear cardiovascular protective effects. This paper summarizes the research progress on the pathogenesis the pathogenesis of COVID-19 in cardiovascular damage by 2019 novel coronavirus(2019-nCoV) virus from myocardial cell injury directly by 2019-nCoV virus,viral ligands competitively bind to ACE2 and then reduce the protective effect of ACE2 on cardiovascular disease, "cytokine storm" related myocardial damage, arrhythmia and sudden cardiac death induced by the infection and stress, myocardial injury by hypoxemia, heart damage side effects from COVID-19 drugs and summarizing the cardiovascular protective effects of artemisinin and its derivatives have activities of anti-arrhythmia, anti-myocardial ischemia, anti-atherosclerosis and plaque stabilization. Then analyzed the possible multi-pathway intervention effects of artemisinin-based drugs on multiple complications of COVID-19 based on its specific immunomodulatory effects, protective effects of tissue and organ damage and broad-spectrum antiviral effect, to provide clues for the treatment of cardiovascular complications of COVID-19, and give a new basis for the therapy of COVID-19 through "drug repurposing".

Current advances in research on adjuvant therapy for cerebral malaria / 药学学报

Cerebral malaria (CM) is the deadliest complication of Plasmodium falciparum infection and even with effective anti-malarial treatment the mortality of children can be as high as 18%; up to one-third of CM survivors are left with neurological and cognitive deficits. The pathophysiology of CM is not completely understood, but mechanical obstruction and immunopathology are its mainstream theories. Adjuvant therapy aims to improve clinical outcomes and/or reduce mortality, as well as preventing long-term neurocognitive deficits. Improving survival and reducing neurological damage to survivors are new goals for new antimalarials and adjuvant therapies. Herein, we discussed what is known about the disease mechanism of CM and systematically summarize the progress of adjuvant therapy research in protecting the vascular endothelium, reducing adhesion formation, regulating immune balance, interfering with malarial metabolism, protecting nerves, improving nitric oxide bioavailability, improving energy metabolism and alleviating inflammation, with the aim of exploiting this understanding to reduce the neurological damage to children with CM. This work also highlights some preclinical studies which may be candidate strategies in future clinical trials.

Method for rapid synchronization of different growth cycles of Plasmodium falciparum in vitro and application in differential gene expression profile of 3D7 after dihydroartemisinin treatment / 中国中药杂志

Plasmodium culture in vitro is often used as an antimalarial drug evaluation model, but the lifecycle of P. falciparum culture in vitro tends to be disordered, which affects the research and evaluation of antimalarial drug mechanism in vitro. By combining magnetic bead separation method with sorbitol synchronization method, a synchronization method was constructed to quickly acquire different lifecycles of P. falciparum and obtain large amounts of parasite with a narrow synchronization window in a short period. Furthermore, the dihydroartemisinin(DHA) was used to treat the early trophozoite phase of P. falciparum 3 D7 for 4 h. Then mRNA was extracted and RNA-seq was conducted to analyze the differential expression of mRNA after drug treatment and obtain the differential gene expression profile. Differential expression of up-regulated genes and down-regulated genes was analyzed according to the screening criteria of |log_2FC|>1 and P<0.05. There, 262 genes were up-regulated and 77 genes were down-regulated. GO functional enrichment analysis of all the differentially expressed genes showed that the enrichment items mainly included cell membrane components, transporter activity, serine/threonine kinase activity, Maurer's clefts(MCs), rhoptry, antigen variation and immune evasion. The enrichment of KEGG pathway included malaria, fatty acid metabolism and peroxisome. Protein-protein interaction(PPI) analysis showed that the down-regulated genes in the modules with high degree of association included rhoptry, myosin complex, transporter and other genes related to the important life activities of malaria invasion and immune escape; the up-regulated genes were mainly related to various toxic exportins of malaria, such as PfSBP1 of MCs. qRT-PCR was used to verify the expression level of some genes, and most of the results were the same as the sequencing results. SBP1 was significantly up-regulated, while some antigenic protein expression levels were down-regulated. Above all, key molecules of DHA therapy were mainly involved in the parasites' rhoptry, transporter, antigenic variation, plasmodium exportin. These results offer us many hints to guide the further studies on mechanism of artemisinin and provide a new way for development of new antimalarial drugs.

Comparison of VEGF-A, PDGF and PEDF levels in aqueous humor and serum of patients with neovascular glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To quantitatively measure and evaluate the VEGF-A, platelet derived growth factor(PDGF)and pigment epithelium derired factor(PEDF)in the aqueous humor of patients with neovascular glaucoma(NVG). <p>METHODS: Prospectively clinical study. This study involved 23 eyes of 23 patients with advanced NVG and 23 control subjects with age related cataract. Protein concentrations of VEGF-A, PDGF and PEDF in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay(ELISA)tests. <p>RESULTS: The VEGF-A and PDGF concentrations in aqueous humor from NVG patients were(1130.56±69.32)ng/L and(221.95±56.08)ng/L, respectively. Both of them were significantly higher than control subject(226.45±37.46)ng/L,(36.25±7.12)ng/L(<i>P</i><0.01). Aqueous PEDF was significantly lower in the NVG group(195.69±42.00)ng/L than that in controls(497.89±12.52)ng/L(<i>P</i><0.01). However, levels of VEGF-A, PDGF and PEDF in the serum of NVG were(226.45±37.46)ng/L,(29.57±6.31)ng/L and(13.24±1.76)ng/L, respectively, which were similar with control subjects(219±34.89)ng/L,(28.28±7.24)ng/L and(12.96±2.08)ng/L(<i>P</i>>0.05). The concentrations of VEGF-A were closely positive correlated with levels of PDGF in the aqueous humor of patients with NVG(<i>r</i>=0.502, <i>P</i>=0.015). However, the concentrations of VEGF-A were closely negative correlated with levels of PEDF in the aqueous humor of patients with NVG(<i>r</i>=-0.480, <i>P</i>=0.020). <p>CONCLUSION: There were higher levels of VEGF-A and PDGF, and lower level of PEDF in the aqueous humor of patients with NVG. There was a positive correlation between VEGF-A and PDGF, a negative correlation between VEGF-A and PEDF. The combination of anti-VEGF agent, PDGF inhibitor and PEDF may provide a new idea for the treatment of NVG.

Protective Effect of Artemisinin on Mice with Systemic Inflammatory Response Syndrome / 中国实验方剂学杂志

Objective:To study the protective effect and mechanism of artemisinin on systemic inflammatory response syndrome （SIRS）mice using endotoxin （LPS）-induced SIRS mouse model. Method:Male BALB/c mice aged 5-7 weeks were randomly divided into normal group， LPS model group， low， medium and high-dose artemisinin groups （25， 50， 100 mg·kg-1） and ibuprofen group （39 mg·kg-1）. LPS （10 mg·kg-1） was intraperitoneally injected at the 7th day after the prophylaxis. According to the SIRS clinical diagnostic criteria， the respiratory rate， rectal temperature， lung index， spleen index， glycolipid metabolism， brain tissue inflammatory factors， and phosphorylation of lung tissue inflammation-related proteins were measured. Result:Intraperitoneal injection of LPS significantly reduced the respiratory rate of mice （P<0.05）， body temperature decreased significantly （P<0.01）， spleen index increased significantly （P<0.01）， peripheral blood neutrophil percentage increased significantly （P<0.05）， percentage of monocytes decreased significantly （P<0.01）， thrombocyte decreased （P<0.01）， platelet specific ratio decreased （P<0.01）， total cholesterol content in plasma decreased （P<0.01）， plasma glucose content decreased （P<0.01）. The expression of interleukin-1β increased in hippocampus and cortex of brain tissue （P<0.01）， and the secretion of tumor necrosis factor-α increased in hippocampus and cortex of brain tissue （P<0.01）. The expression of phosphorylated protein STAT1 was increased （P<0.01）， and the expression of phosphorylated protein c-Jun was increased （P<0.01）. After the administration of artemisinin， the body temperature and the respiratory rate of mice induced by LPS were significantly increased， the pathological changes of various organs induced by LPS were alleviated， the hypoglycemia induced by LPS was significantly increased （P<0.05）， the levels of inflammatory factors in hippocampus and cortex was significantly reduced， and the expressions of phosphorylated proteins STAT1 and c-Jun in lung tissue were significantly reduced （P<0.05， P<0.01）. Conclusion:Artemisinin has a significantly protective effect on SIRS mice induced by intraperitoneal injection of LPS possibly by reducing the secretion of inflammatory factors TNF-α and IL-1β.

Mechanism of Shengmaiyin (Dangshen Prescription) in Treatment of Atherosclerotic Cardiovascular Disease Based on Network Pharmacology / 中国实验方剂学杂志

Objective:By means of network pharmacology, the active ingredients, targets and molecular pathways of Shengmaiyin (Dangshen prescription) in the treatment of atherosclerotic cardiovascular disease (ASCVD) were studied, in order to reveal the molecular mechanism of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD, and provide the rational explanation of the compatibility of the combination. Method:The main chemical components of Shengmaiyin (Dangshen prescription) were obtained by means of SymMap database, traditional Chinese medicine systems pharmacology database and analysis platform（TCMSP）platform and BATMAN-TCM platform. Compound targets were retrieved by SymMap and the Encyclopedia of Traditional Chinese Medicine （ETCM）, and disease targets were retrieved by DisGeNET and GeneCards databases. The intersections of compound targets and disease targets were used to obtain the predicted targets of song-decoction on ASCVD. The Protein-Protein Interaction (PPI) network diagram was constructed through STRING database, and key compounds and targets of Shengmaiyin (Dangshen prescription) acting on ASCVD were obtained through Cytoscape. Finally, the enriched key targets were put for Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis through the Database for Annotation，Visualization and Integrated Discovery（DAVID）. Result:There were 33 key compounds and 25 key targets of Shengmaiyin (Dangshen prescription) for ASCVD. The GO analysis showed that the biological functions of Shengmaiyin (Dangshen prescription) in the treatment of key ASCVD targets mainly involved biological processes, such as the regulation of apoptosis, inflammatory response, regulation of nitric oxide synthesis and regulation of insulin secretion. The KEGG pathway was mainly enriched in 20 signaling pathways, including tumor necrosis factor(TNF) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, apoptosis signaling pathway and estrogen signaling pathway. Conclusion:Through network pharmacology, this study explored active ingredients and potential targets of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD at the molecular level, preliminarily verified the mechanism of action of Shengmaiyin (Dangshen prescription), and laid a theoretical foundation for further study on the mechanism of action.

Relationship Between Immune Checkpoint and Autoimmune Disease / 中国实验方剂学杂志

The normal immune system has the ability to distinguish between "self" and "non-self". Because of its dynamic balance of "immune activity-immune tolerance", it will produce immune response to the non-self antigen, but with no response or weak response to the self-antigen. However, if the balance was broken, T cell in the abnormal immune activation state will respond continually to the self-antigen, with an abnormal immune response, which caused autoimmune disease. Pathologically, "invalid" immune recognition and immune response become the main causes for autoimmune diseases. Co-stimulatory molecule is an important link between Attach antigen presenting cells（APC） and immune cells (T cell and B cell). Studies have proved that excessive co-stimulation and/or insufficient co-inhibition could cause detect of self-tolerance and induce autoimmunity. Although co-stimulatory and co-inhibitory pathways have a significant impact on all ADS, this paper focuses on their effect on two systemic autoimmune diseases [systemic lupus erythematosus （SLE） and rheumatoid arthritis（RA）] and two organ-specific autoimmune diseases [multiple sclerosis （MS） and type 1 diabetes （T1DM）], in order to discuss the pathogenesis and relationship between co-stimulatory molecules and autoimmune diseases.

Research advancement in natural anti-cancer product / 中国中药杂志

Human health has been severely threatened by malignant tumors continuously.Rational and effective drug use provides an effective means for the treatment of malignant tumors,and is expected to become an important way to solve the problem of tumor treatment in the future.In recent years,with the escalation of new cancer theories and the emergence of clinical drug resistance,innovative research and development of anti-cancer drugs has always been a hot spot and focus in cancer research.Among them,the discovery of novel anti-cancer drugs from natural compound is of top priority due to its strong anti-cancer efficacy and the abundant drug resources.Therefore,it is imperative to systematically summarize the cutting-edge advancements of the natural products and their potential pharmacological mechanisms according to the characteristics of tumor progression,and put forward the new directions and trends for further development of anti-cancer natural products in the future.Specifically,the research advancements on anti-cancer effect of natural products were reviewed,focusing on both the traditional and innovative application.We hope this review could bring the light on the research path of the natural anti-cancer products clearly and comprehensively,and also provide inspirations for innovative,safer and more effective anti-cancer drug development and exploration.