OBJECTIVE: To analyze the intellectual landscape and emerging research trends of Chinese medicine (CM) in the management of pediatric asthma through a scientometric study. METHODS: Publications related to CM in the management of pediatric asthma were retrieved from the Web of Science Core Collection using relevant keywords. A scientometric study was performed using CiteSpace and VOSviewer. RESULTS: A total of 1,673 original articles and reviews from 1991 to 2019 were included in the analysis. The amount of annual publications had a gradual increase with time. USA was the major contributor both in country and institution analyses. Based on the co-citation, the published journals were grouped into 4 clusters. Keyword analysis indicated that the main hotspots were: (1) comprehensive management; (2) risk factors, mechanism, and prevalence; (3) prevention and treatment; (4) inflammation; and (5) environmental research. Lastly, we predicted that three emerging trends were quality of life promotion, immune response, and combination therapy. CONCLUSIONS CM research in the management of pediatric asthma will maintain the current trend of steady growth. This scientometric analysis may help scientists to identify the areas of interests and future directions in the field.
Asthma/drug therapy* ; Bibliometrics ; Child ; Humans ; Medicine, Chinese Traditional ; Publications ; Quality of Life

Objective: To investigate the effects of continuous goal-directed analgesia on fluid resuscitation during shock stage in patients with massive burns, providing a basis for rational optimization of analgesia protocols in patients with burn shock. Methods: A retrospective case series study was conducted. One hundred and thirty-six patients with massive burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital from January 2015 to December 2020, and the patients were divided into continuous analgesia (CA) group (68 cases,with average age of 44 years old) and intermittent analgesia (IA) group (68 cases,with average age of 45 years old) according to whether sufentanil injection was continuously used for intravenous analgesia during the shock stage. The patients in the 2 groups were predominantly male. Before and at 72 h of treatment, the severity of disease and trauma pain of patients in the 2 groups were scored by the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and the visual analogue scale (VAS). Hematocrit, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), oxygen saturation in central venous blood (ScvO₂), rehydration coefficient, blood lactate value, hourly urine output, and the adverse reactions such as hypotension, nausea, vomiting, dizziness, skeletal muscle tonicity, respiratory depression, bradycardia, pruritus, and drug addiction of patients in the 2 groups during the treatment were recorded at the 1^st, 2^nd, and 3^rd 24 h post-injury. Data were statistically analyzed with analysis of variance for repeated measurement, paired or independent sample t test, Bonferroni correction,chi-square test and Mann-Whitney U test. Results: Before treatment, APACHE Ⅱ and VAS scores of patients in the 2 groups were close (with t values of -0.67 and 0.32, respectively, P>0.05); At 72 h of treatment, APACHE Ⅱ and VAS scores of patients in CA group were 8.5±2.2 and 2.5±1.6, both of which were significantly lower than (15.2±3.0) and (7.9±2.0) of patients in IA group, respectively (with t values of -14.94 and -17.46, respectively, P<0.01). Compared with the pre-treatment period, the APACHE Ⅱ and VAS scores of patients in IA group decreased significantly at 72 h of treatment (with t values of 11.35 and 30.59, respectively, P<0.01); the changes in APACHE Ⅱ and VAS scores of patients at 72 h of treatment in comparison with those of patients before treatment in CA group were all similar to those of patients in IA group (with t values of 4.00 and 4.82, respectively, P<0.01). Compared with those of patients in IA group, there were no significant changes in CVP, hematocrit, heart rate, ScvO₂, and MAP of patients in CA group at all three 24 h post-injury (with t values of <0.01, 0.12, 2.10, 1.55, 0.03; 0.13, 0.22, <0.01, 0.17, 0.49; 0.63, 0.06, 0.04, 2.79, and 2.33, respectively, P>0.05). Compared with those of patients in IA group at the 1^st 24 h post-injury, CVP, ScvO₂ and MAP of patients were significantly higher at the 2^nd and 3^rd 24 h post-injury (with t values of -10.10, -9.31, -8.89; -10.81, -4.65, and -9.43, respectively, P<0.01), and the heart rate of patients was significantly lower at the 2^nd and 3^rd 24 h post-injury (with t values of 7.53 and 7.78, respectively, P<0.01), and the hematocrit of patients decreased significantly only at the 3^rd 24 h post-injury (t=15.55, P<0.01); the changes of CVP, ScvO₂, MAP and heart rate of patients at the 2^nd and the 3^rd 24 h post-injury, and HCT of patients at the 3^rd 24 h post-injury, in comparison with those of patients at the 1^st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of -12.25, -10.24, -8.99, 9.42, -8.83, -7.53, -11.57, 10.44, and 12.91, respectively, P<0.01). Compared with those of patients in IA group, the rehydration coefficient of patients in CA group was significantly higher only at the 3^rd 24 h post-injury (t=5.60, P<0.05), blood lactate value of patients in CA group was significantly lower at the 1^st and 2^nd 24 h post-injury (with t values of 4.32 and 14.52, respectively, P<0.05 or P<0.01), the hourly urine output of patients in CA group increased significantly at the 1^st, 2^nd, and 3^rd 24 h post-injury (with t values of 24.65, 13.12, and 5.63, respectively, P<0.05 or P<0.01). Compared with the those of patients at the 1^st 24 h post-injury, the rehydration coefficient of patients in IA group decreased significantly at the 2^nd and the 3^rd 24 h post-injury (with t values of 33.98 and 36.91, respectively, P<0.01), the blood lactate values of patients in IA group decreased significantly at the 2^nd and the 3^rd 24 h post-injury (with t values of 8.20 and 11.68, respectively, P<0.01), and the hourly urine output of patients in IA group was significantly increased at the 2^nd and the 3^rd 24 h post-injury (with t values of -3.52 and -5.92, respectively, P<0.01); the changes of rehydration coefficients and blood lactate values of patients at the 2^nd and the 3^rd 24 h post-injury in comparison with those of patients at the 1^st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of 35.64, 33.64, 9.86, and 12.56, respectively, P<0.01), but hourly urine output of patients in CA group increased significantly only at the 3^rd 24 h compared with that of patients at the 1^st 24 h post-injury (t=-3.07, P<0.01). Adverse reactions such as hypotension, nausea, vomiting, dizziness, bradycardia, and pruritus occurred rarely in patients of the 2 groups, and none of the patients had skeletal muscle tonicity, respiratory depression, or drug addiction. The incidence of adverse reactions of patients in CA group was similar to that in IA group (χ²=0.08, P>0.05). Conclusions: Continuous goal-directed analgesia can effectively relieve pain and improve vital signs of patients with large burns. Meanwhile it has little impact on volume load, which can assist in correcting ischemia and hypoxia during the shock period and help patients get through the shock period smoothly.
Adult ; Analgesia ; Burns/therapy* ; Fluid Therapy ; Goals ; Humans ; Male ; Middle Aged ; Pain ; Resuscitation ; Retrospective Studies ; Shock/therapy*

OBJECTIVE：To explo re the potential molecular mechanism of ursolic acid in the treatment of osteoporosis （OP）. METHODS：TCMSP，PubMed database and UniProt database were used to screen potential targets of monomer compound ursolic acid. OP related target genes were searched with GeneCards database. The common target genes of component-disease were obtained by Venny 2.1 online mapping tool. The protein-protein interaction （PPI）network of component-disease common target genes was constructed by using STRING database ，and topological analysis was carried out ；the core target genes ，whose degree value was greater than the average degree value ，were screened. GO functional annotation and KEGG pathway enrichment analysis of component-disease common target genes were carried out by DAVID database. AutoDock Vina 1.1.2 software was used for molecular docking ，using protein encoded by the core target gene as receptor and ursolic acid as ligand. RESULTS ：A total of 55 ursolic acid related target genes and 4 273 OP related target genes were excavated ，with a total of 44 common target genes. PPI network with above common target genes included 44 nodes and 513 edges，with an average node degree of 23.3. There were 24 core target genes ，including VEGFA，TP53，IL6，CASP3. There were 340 GO functional items were enriched （corrected P＜ 0.05），including 263 biological processes （negative regulation of apoptosis ，etc.），25 molecular functions （protein binding ，etc.） and 52 cell components （cytosol，etc.）. There were 90 KEGG signaling pathways （corrected P＜0.05），such as tumor pathway ， hepatitis B pathway ，TNF signaling pathway ，viral carcinogenesis and phosphatidylinositol 3 kinase/protein kinase B （PI3K-Akt） signaling pathway. The binding energy between ursolic acid and 6 proteins encoded by core target genes such as TP53 was lower than －5 kcal/mol，which had strong binding activity. CONCLUSIONS ：The therapeutic effect of ursolic acid on OP may be achieved by regulating VEGFA，TP53，IL6，CASP3，JUN and other core target genes and acting on multiple key pathways such as cancer pathway ， hepatitis B and TNF signaling

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.
Antimalarials/pharmacology* ; Artemisinins/therapeutic use* ; Humans ; Lipid Metabolism ; Malaria/drug therapy* ; Plasmodium

Objective:To explore the inhibitory effect of dihydroartemisinin （DHA） on the proliferation of HepG2 cells， elucidate the mechanism from the perspectives of oxidative damage and energy metabolism， and discuss the possibility of combined use of DHA with sorafenib （Sora）. Method:Cell counting kit-8 （CCK-8） assay was used to obtain the 50% inhibitory concentration （IC₅₀） of DHA and Sora on HepG2 and SW480 cells and Chou-Talalay method was used to obtain the combination index （CI） of DHA and Sora. HepG2 cells were classified into the control group， DHA group （10 µmol·L^-1）， Sora group （5 µmol·L^-1）， and DHA + Sora group （DHA 10 µmol·L^-1， Sora 5 µmol·L^-1） and then incubated with corresponding drugs for 8-12 h. Seahorse XF glycolytic rate assay kit and cell mito stress test kit were employed to respectively detect the glycolysis function of cells and oxidative phosphorylation function of mitochondria. DCFH-DA and lipid peroxidation MDA assay kit were separately used to analyze the intracellular levels of reactive oxygen species （ROS） and malondialdehyde （MDA）. Western blot was applied to determine the intracellular levels of heme oxygenase-1 （HO-1） and glutamate-cysteine ligase catalytic subunit （GCLC）. Result:Compared with the control group， DHA alone inhibited the ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （P<0.01）， increased the levels of intracellular ROS and MDA （P<0.05）， and decreased the levels of HO-1 and GCLC （P<0.05） in HepG2 cells. DHA and Sora had synergistic inhibitory effect on proliferation of HepG2 and SW480 cells， with CI < 0.90. The DHA + Sora group showed stronger suppression of ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （P<0.01）， higher levels of intracellular ROS and MDA （P<0.01）， and lower levels of intracellular antioxidation-related proteins HO-1 and GCLC in HepG2 cells （P<0.01） than the DHA group. Conclusion:DHA may increase the level of MDA by reducing HO-1 and GCLC and increasing ROS in HepG2 cells， which results in mitochondria oxidative damage， restricts cell glycolysis and mitochondrial oxidative phosphorylation， and thus finally inhibits the proliferation of HepG2 cells. DHA and Sora have synergistic inhibitory effect on the proliferation of HepG2 and SW480 cells， and the mechanism may be related to the synergistic oxidative damage that affects the mitochondrial electron transport chain and suppresses cell energy metabolism.

The resistance to artemisinin generated by plasmodium is defined as follows: After being treated with ACTs for three days, the time to clear plasmodium from the blood of patients with malaria becomes prolonged. The elimination rate of plasmodium in vivo is not only related to the parasiticidal efficacy of antimalarial drugs, but also affected by biological factors such as the mutation of plasmodium themselves, the regulation of human immune function(such as the recognition and processing of phagocytes) , and the efflux of foreign l>odies from immune organs. This article primarily reviews the mutation of plasmodium themselves , the physical and biochemical process of the spleen eliminating plasmodium, including K13 changes, the two blood circulation pathways of the spleen. Since the endothelial cell gap of the splenic venous sinus is elastic, plasmodium or red blood cell debris can be trapped by physical and mechanical sensing methods. The red pulp is the main venue to filter blood, where the immune cells are responsible for the removal of the residues of plasmodium. The physical process of the splenic venous sinus trapping plasmodium is called pitting, and its incidence is influenced by the growth cycle of plasmodium and therapeutic drugs. In this paper, the function of the spleen to eliminate plasmodium will be explained, in an attempt to provide a reference for the biological nature of the artemisinin resistance generated by plasmo-dium.

Taxol is a "blockbuster" antitumor drug produced by species with extremely low amount, while its analogue 7--xylosyl-10-deacetyltaxol is generally much higher in the plants. Both the fungal enzymes LXYL-P1-1 and LXYL-P1-2 can convert 7--xylosyl-10-deacetyltaxol into 10-deacetyltaxol for Taxol semi-synthesis. Of them, LXYL-P1-2 is twice more active than LXYL-P1-1, but there are only 11 significantly different amino acids in terms of the polarity and acidic-basic properties between them. In this study, single and multiple site-directed mutations at the 11 sites from LXYL-P1-1 to LXYL-P1-2 were performed to define the amino acids with upward bias in activities and to acquire variants with improved catalytic properties. Among all the 17 mutants, E12 (A72T/V91S) was the most active and even displayed 2.8- and 3-fold higher than LXYL-P1-2 on -xylosidase and -glucosidase activities. The possible mechanism for such improvement was proposed by homology modeling and molecular docking between E12 and 7--xylosyl-10-deacetyltaxol. The recombinant yeast GS115-P1E12-7 was constructed by introducing variant , the molecular chaperone gene and the bacterial hemoglobin gene . This engineered yeast rendered 4 times higher biomass enzyme activity than GS115-3.5K-P1-2 that had been used for demo-scale fermentation. Thus, GS115-P1E12-7 becomes a promising candidate to replace GS115-3.5K-P1-2 for industrial purpose.

Heme is a key metabolic factor in all life. Malaria parasite has de novo heme-biosynthetic pathway, however the growth and development of parasite depend on the hemoglobin-derived heme metabolism process during the intraerythrocytic stages, such as the ingestion and degradation of hemoglobin in the food vacuole. The hemoglobin metabolism in the food vesicles mainly includes four aspects: hemoglobin transport and intake, hemoglobin enzymolysis to produce heme, heme polymerization into malarial pigment, and heme transport via the food vacuole. The potential mechanisms of antimalarial drugs,such as chloroquine, artemisinin and atovaquone may be related to this process. The main four aspects of this metabolic process, key metabolic enzymes, effects of antimalarial drugs on the process and their potential mechanism of action would be summarized in this paper, providing ideas for rational use and mechanism exploration of similar drugs.

Ferroptosis is a new form of regulated cell death which is different from apoptosis, necrosis and autophagy, and results from iron-dependent lipidperoxide accumulation. Now, it is found that ferroptosis is involved in multiple physiological and pathological processes, such as cancer, arteriosclerosis, neurodegenerative diseases, diabetes, antiviral immune response, acute renal failure, hepatic and heart ischemia/reperfusion injury. On the one hand, it could be found the appropriate drugs to promote ferroptosis to clear cancer cells and virus infected cells, etc. On the other hand, we could inhibit ferroptosis to protect healthy cells. China has a wealth of traditional Chinese medicine resources. Chinese medicine contains a variety of active ingredients that regulate ferroptosis. Here, this paper reported the research of ferroptosis pathway, targets of its inducers and inhibitors that have been discovered, and the regulatory effects of the discovered Chinese herbs and its active ingredients on ferroptosis to help clinical and scientific research.
Apoptosis ; China ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Iron ; Materia Medica ; pharmacology

The main objective of this research is to observe protective effects of three phenylallyl compounds(cinnamyl alcohol,cinnamaldehyde and cinnamic acid)from Guizhi decoction against ox-LDL-induced oxidative stress injury on human brain microvascular endothelial cells(HBMEC).In this study,the toxicity and optimal protective concentration of three phenylallyl compounds from Guizhi decoction were determined by MTT assay.The HBMEC were divided into control group(DMSO),model group(ox-LDL),tert-butylhydroquinone (t-BHQ) group,cinnamyl alcohol group, cinnamaldehyde group and cinnamic acid group.The model group were treated with ox-LDL (50 mg•L⁻¹)for 24 h,other groups were separately treated with t-BHQ, cinnamyl alcohol, cinnamaldehyde and cinnamic acid of 20 μmol•L⁻¹, and exposed to ox-LDL (50 mg•L⁻¹) for 24 h at the same time.The survival rate of HBMEC was detected by MTT assay,reactive oxygen species(ROS) production of injured cells were detected using laser scanning confocal microscope (LSCM),the content of SOD, MDA, eNOS and NO in HBMEC was determined by ELISA, and the expressions of Nrf2 mRNA were detected by quantitative Real-time PCR(qRT-PCR).The results shows that oxidative stress injury of HBMEC could be induced by ox-LDL, the three phenylallyl compounds from Guizhi decoction did not affect morphology and viability of normal HBMEC.Compared with model group, the three phenylallyl compounds from Guizhi decoction could improve the above oxidative stress status and up-regulate Nrf2 mRNA expressions in injured HBMEC(P<0.05, P<0.01) .These findings suggested that the three phenylallyl compounds from Guizhi decoction have certain protective effects against ox-LDL-induced oxidative stress injury on HBMEC(cinnamaldehyde> t-BHQ> cinnamic acid>cinnamyl alcohol),the protective mechanism maybe related to regulation of antioxidant enzymes gene expression in HBMEC by Nrf2.