Effect of Curcumin on Apoptosis of Acute T-Lymphoblastic Leukemia Cells induced by UMI-77 and Its Related Mechanism / 中国实验血液学杂志

AbstractObjective: To explore the effect and mechanism of curcumin on human T-cell acute lymphoblastic leukemia (T-ALL) cell apoptosis induced by Mcl-1 small molecule inhibitors UMI-77.@*METHODS@#T-ALL cell line Molt-4 was cultured, and the cells were treated with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77 for 24 h. The MTT method was used to detect the cell survival rate after different treatment; According to the results of curcumin and UMI-77, the experimental settings were divided into control group, curcumin group (20 μmol/L curcumin treated cells), UMI-77 group (15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells) and curcumin+ UMI-77 group (20 μmol/L curcumin and 15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells), MTT method was used to detect cell proliferation inhibition rate, Annexin V-FITC/PI double staining method and TUNEL staining were used to detect cell apoptosis, DCFH-DA probe was used to detect cell reactive oxygen species, JC-1 fluorescent probe was used to detect mitochondrial membrane potential, Western blot was used to detect the expression levels of apoptosis-related proteins and Notch1 signaling pathway-related proteins.@*RESULTS@#After the treatment of Molt-4 cells with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77, the cell survival rate was decreased (P<0.05); Compared with the control group, the cell proliferation inhibition rate of the curcumin group and the UMI-77 group were increased, the apoptosis rate of cell was increased, the level of ROS was increased, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, and the protein expression of Bcl-2 was reduced (P<0.05); Compared with the curcumin group or UMI-77 group, the cell proliferation inhibition rate and apoptosis rate of the curcumin+UMI-77 group were further increased, and the level of ROS was increased. At the same time, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, the protein expression of Bcl-2 was reduced (P<0.05); In addition, the mitochondrial membrane potential of the cells after curcumin treatment was decreased, and the proteins expression of Notch1 and HES1 were reduced (P<0.05).@*CONCLUSION@#Curcumin can enhance the apoptosis of T-ALL cells induced by Mcl-1 small molecule inhibitor UMI-77 by reducing the mitochondrial membrane potential, the mechanism may be related to the inhibition of Notch1 signaling pathway.

Interference of P2X4 receptor expression in tumor-associated macrophages suppresses migration and invasion of glioma cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of interference of P2X4 receptor expression in tumor-associated macrophages (TAMs) on invasion and migration of glioma cells.@*METHODS@#C57BL/6 mouse models bearing gliomas in the caudate nucleus were examined for glioma pathology with HE staining and expressions of Iba-1 and P2X4 receptor with immunofluorescence assay. RAW264.7 cells were induced into TAMs using conditioned medium from GL261 cells, and the changes in mRNA expressions of macrophage polarization-related markers and the mRNA and protein expressions of P2X4 receptor were detected with RT-qPCR and Western blotting. The effect of siRNA-mediated P2X4 interference on IL-1β and IL-18 mRNA and protein expressions in the TAMs was detected with RT-qPCR and Western blotting. GL261 cells were cultured in the conditioned medium from the transfected TAMs, and the invasion and migration abilities of the cells were assessed with Transwell invasion and migration experiment.@*RESULTS@#The glioma tissues from the tumor-bearing mice showed a significantly greater number of Iba-1-positive cells, where an obviously increased P2X4 receptor expression was detected (P=0.001), than the brain tissues of the control mice (P < 0.001). The M2 macrophage markers (Arg-1 and IL-10) and M1 macrophage markers (iNOS and TNF-α) were both significantly up-regulated in the TAMs derived from RAW264.7 cells (all P < 0.01), but the up-regulation of the M2 macrophage markers was more prominent; the expression levels of P2X4 receptor protein and mRNA were both increased in the TAMs (P < 0.05). Interference of P2X4 receptor expression significantly lowered the mRNA(P < 0.01)and protein (P < 0.01, P < 0.05)expression levels of IL-1β and IL-18 in the TAMs and obviously inhibited the ability of the TAMs to promote invasion and migration of the glioma cells (P < 0.05).@*CONCLUSION@#Interference of P2X4 receptor in the TAMs suppresses the migration and invasion of glioma cells possibly by lowering the expressions of IL-1β and IL-18.

Megastigmanes from an aqueous extract of Uncaria rhynchophylla / 药学学报

Five new megastigmanes (1-5) were isolated from a decoction of Uncaria rhynchophylla by separation techniques of column chromatography using a combination of multiple stationary phases, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40F, and reversed phase HPLC. Their structures were characterized by spectroscopic data analysis of HR-ESI-MS, NMR, and CD, in combination with Mosher's mothed as well as ECD and NMR calculations. The new compounds were named uncarphyllonone A (1), uncarphyllonols A (2) and B (3), and uncarphabscisic acids A (4) and B (5). Although the structures of 3 and 4 were previously reported, the reported NMR spectroscopic data were incorrect or do not support the assigned structures in literatures. This is also the first report of discovery of new megastigmane natural products from the Uncaria genus.

Ferroptosis of airway epithelial cells in asthma: current and future / 药学学报

Ferroptosis is a novel cell death mode proposed in recent years, which is characterized by intracellular iron-dependent lipid peroxidation. Its mechanisms include lipid peroxidation, iron accumulation and the imbalance of antioxidant system. The crosstalk between ferroptosis and asthma is gradually deepening. Elucidating the specific mechanism of ferroptosis in regulating asthma is helpful to broaden the understanding of the pathology of asthma. This paper expounds the role of ferroptosis in airway epithelial cells in the occurrence and development of asthma from three perspectives: lipid peroxidation, iron accumulation and the imbalance of antioxidant system, hoping to find new targets and strategies for asthma treatment.

Progress of discovery of molecular glues from natural products and their derivatives / 药学学报

Molecular glues are a class of small molecules that induce the formation of protein-protein interactions to confer new biological function or therapeutic effects. As a unique pharmacological modality, molecular glues could target proteins without druggable binding pockets. It exhibits a variety of functions, including regulating signal transduction, stabilization or degradation of targeted proteins, through sticking different proteins together. This review will summarize the development and current status of molecular glues derived from natural products and analogs by illustrating the discovery and interaction mechanism. We hope to present a systematic view, provide valuable clues for researchers and encourage them to explore more efficient and rational molecular glue discovery strategies.

Study on regulation of CYP450 enzyme system to reduce liver toxicity through compatibility of Aconiti Kusnezoffii Radix Cocta with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma / 中国中药杂志

Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.

Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway / 中国中药杂志

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

Diagnostic Cut-Off Value of RDW for Screening Thalassemia and the Combined Determination of MCV, MCH, HBA / 中国实验血液学杂志

OBJECTIVE@#To explore the value of red cell distribution width (RDW), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin (Hb) A2 combined determination scheme for screening thalassemia.@*METHODS@#The RDW levels of thalassemia group and healthy control group were detected and compared. The efficiency of RDW for screening thalassemia was evaluated by receiver operating characteristic (ROC) curve. The diagnostic cut-off value of RDW was also acquired by Youden index. Then, 3 groups for thalassemia screening scheme were set, including MCV+MCH+HBA @*RESULTS@#The RDW level in thalassemia group was significantly higher than that in healthy control group (P15.15, when the Youden index was the biggest among all data. The sensitivity, specificity, positive predictive value, negative predictive value, false negative rate and consistency rate of MCV+MCH+RDW(>15.15)+HBA @*CONCLUSION@#The diagnostic cut-off value of RDW for thalassemia screening has been established. The group of MCV(<82.0 fl)+MCH(<27.0 pg)+HBA

Relationship between IKZF3 Gene Single Nucleotide Polymorphisms and Childhood Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between single nucleotide polymorphisms (SNPs) of IKAROS family Zinc finger 3 (IKZF3) gene and the risk of acute lymphoblastic leukemia (ALL) in children.@*METHODS@#The peripheral blood samples from 286 children with ALL and 382 healthy children were collected and divided into ALL group and control group, respectively. The genotypes of IKZF3 gene at rs62066988 C > T and rs12946510 C > T were detected by quantitative PCR with TaqMan detection system, and their correlation with ALL was analyzed.@*RESULTS@#The distribution frequencies of CC, CT and TT genotypes at rs62066988 in ALL group were 58.39%, 37.06% and 4.55%, respectively, while those in control group were 69.19%, 27.68% and 3.13%, respectively. The distribution frequencies of CC, CT and TT genotypes at rs12946510 in ALL group were 58.16%, 34.75% and 7.09%, respectively, while those in control group were 55.76%, 37.43% and 6.81%, respectively. Compared with the control group, the distribution frequency of CT/TT genotype at rs62066988 was significantly increased in the ALL group (OR=1.59, 95%CI: 1.16-2.19, P=0.004). However, there was no significant difference in the distribution of rs12946510 C > T polymorphism between ALL group and control group.@*CONCLUSION@#The CT/TT genotype of IKZF3 at the site of rs62066988 is associated with the increased risk of ALL in children.

Pharmacokinetic/pharmacodynamic modeling of the antitumor action of bispecific CD3/EpCAM antibody M701 in human colorectal cancer xenograft mice / 药学学报

M701 is a bispecific CD3/EpCAM T-cell engager antibody for the treatment of malignant ascites. We developed a population pharmacokinetic/pharmacodynamic (PK/PD) model to quantitatively describe and predict the antitumor effect of M701 in human colorectal cancer xenograft mice. We developed the M701 PK model based on plasma concentration data after i.v. administration. A tumor growth model for human colorectal cancer xenograft was developed to evaluate the antitumor effect of M701. We additionally simulated the inhibitory effect of M701 on tumor volume under different dose regimens based on a PK/PD model. A two-compartment model was developed to predict the PK in human colorectal cancer xenograft mice. The relationship between the M701 concentration and tumor growth inhibition was characterized by a combined Simeoni tumor growth/transit compartment model. The estimated pharmacodynamic parameters were related to the tumor growth characteristics λ0 (0.212 d-1) and λ1 (0.044 7 cm3·d-1), to the drug potency k2 (0.071 5 mL·ng-1·d-1), and to the kinetics of tumor cell death k1 (2×10-5 d-1). A model visual predictive check showed that both the PK model and the tumor growth model closely fit the observed data. Simulated tumor growth after administration of M701 (0.5 mg·kg-1 every 6 days and 0.25 mg·kg-1 every 3 days) could be effectively inhibited. This population PK/PD model of M701 provides insight into the antitumor effect of M701 and supports the further therapeutic development of M701.

Investigation of acupuncture in improving sleep, cognitive and emotion based on attenuation of oxidative stress in prefrontal cortex in sleep-deprived rats / 针灸推拿医学（英文版）

Objective: To explore whether acupuncture can improve sleep disturbance, cognitive impairment and emotional disorders caused by sleep deprivation, and its association with the attenuation of oxidative stress injury in prefrontal cortex. Methods: Fifty-two male Sprague-Dawley rats were randomly divided into a control group (n=10), a model group (n=14), a manual acupuncture (MA) group (n=14), and a sham-MA group (n=14). All the groups were established as sleep deprivation models via the modified multiple platform method, except for the control group. Rats in both the MA group and the sham-MA group received corresponding intervention, respectively. After modeling and intervention, the four groups received three behavioral tests, namely sleep monitoring, by comprehensive lab animal monitoring system (CLAMS), Morris water maze (MWM) test and open-field test (OFT), followed by oxygen free radical level test and Western blot (WB) detection for the expression levels of Bax and Bcl-2. Results: The MA group derived more sleep time within 24 h than either the model group or the sham-MA group (both P<0.05). On MWM orientation navigation test day 1, there were no significant differences in escape latency among the control, MA and sham-MA groups (P>0.05), and the escape latency was significantly shorter in these three groups than that in the model group (all P<0.05). On test day 4, the escape latency was markedly shorter in the MA group than that in either the model group or the sham-MA group (both P<0.05); meanwhile, the MA group showed significantly better performance compared with these two groups in space probe test (both P<0.05). In OFT, compared with the control group, there was a significant decline in the horizontal movement score in the other three groups (all P<0.05), and the decrease was more significant in the model group and the sham-MA group than that in the MA group (both P<0.05). The superoxide dismutase (SOD) content was markedly higher and the malondialdehyde (MDA) content was markedly lower in the MA group than those in the model group and the sham-MA group (all P<0.05). Compared with the model group and the sham-MA group, the expression of Bax was significantly lower and the expression of Bcl-2 was significantly higher in the MA group (all P<0.05). Conclusion: MA therapy can lengthen the sleep time in sleep-deprived rats and improve learning and memory impairments induced by sleep deprivation, and the underlying mechanism may be associated with the enhancement of antioxidant capacity in the prefrontal cortex and the inhibition of hippocampal neuronal apoptosis.

Comparison of Detoxification Effect of Different Solvent Extracts of Lysimachiae Herba on Toxicity Induced by Tripterygii Radix et Rhizoma / 中国实验方剂学杂志

Objective:To investigate the effect of different extracts of Lysimachiae Herba on the main toxicity induced by Tripterygii Radix et Rhizoma. Method:Ninety male SPF Kunming mice were randomly divided into 9 groups according to their body weight，control group， Lysimachiae Herba water extract group， Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba water extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 60% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 95% ethanol extract group and Tripterygii Radix et Rhizoma combined with Lysimachiae Herba ethyl acetate extract group. The dosage of Tripterygii Radix et Rhizoma and Lysimachiae Herba were 2，1 g·kg^-1 based on crude drugs， respectively. The control group was given an equal volume of solvent， and each group was given by gavage for 14 consecutive days. The blood and liver tissues were taken 24 hours after the last administration. The enzyme linked immunosorbent assay （ELISA） was used to detect serum biochemical indexes and liver lipid peroxidation/antioxidant indexes in mice. Meanwhile， principal component analysis was used to evaluate the attenuating effect and the mechanism of Lysimachiae Herba extract on toxicity of Tripterygii Radix et Rhizoma. Result:Compared with control group， Tripterygii Radix et Rhizoma caused the levels of alanine aminotransferase（ALT），aspartic acid amino transferase（AST），alkaline phosphatase（ALP） in serum of mice， and the levels of malondialdehyde （MDA） in liver， and comprehensive score of toxicity （Z value） produced by the above four indexes increased significantly （<italic>P</italic><0.01）. The levels of total superoxide dismutase （T-SOD），glutathione-peroxidase （GPX），glutathione-S transferase （GST） decreased significantly （<italic>P</italic><0.01） in liver. Compared with Tripterygii Radix et Rhizoma group， after intervention with extracts of two solvents （water， 30% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP and liver MDA were significantly decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， while the levels of liver T-SOD， GPX and GST were significantly increased （<italic>P</italic><0.01）. After intervention with extracts of two solvents （60% ethanol， 95% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP were significantly decreased （<italic>P</italic><0.01）， and liver GPX levels were significantly increased （<italic>P</italic><0.01）. After the intervention with ethyl acetate extract of Lysimachiae Herba， only the level of serum AST was significantly decreased （<italic>P</italic><0.05） and the level of GPX was significantly increased （<italic>P</italic><0.05）. After the intervention with extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol， ethyl acetate） of Lysimachiae Herba， it can significantly reduce the comprehensive score of toxicity （<italic>P</italic><0.01）. The overall decline rates of toxicity were 127.5%， 113.4%， 98.1%， 56.3% and 31.0% respectively. Among them， the toxicity reduction rate of the extracts with water as a solvent was 14.1%， 29.4%， 71.2%， 96.5% higher than those of other solvent extracts with ethanol. Conclusion:The extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol and ethyl acetate） of Lysimachiae Herba can reverse the toxicity induced by Tripterygii Radix et Rhizoma in varying degrees. Among them， water and 30% ethanol are the best solvents for detoxification， especially water as the extraction solvent， and with the increase of ethanol content or fat solubility of extraction solvent， the detoxification shows a downward trend.

Identification and expression profiling of R2R3-MYB transcription factors in Erigeron breviscapus / 中国中药杂志

R2 R3-MYB transcription factors are ubiquitous in plants, playing a role in the regulation of plant growth, development, and secondary metabolism. In this paper, the R2 R3-MYB transcription factors were identified by bioinformatics analysis of the genomic data of Erigeron breviscapus, and their gene sequences, structures, physical and chemical properties were analyzed. The functions of R2 R3-MYB transcription factors were predicted by cluster analysis. Meanwhile, the expression patterns of R2 R3-MYB transcription factors in response to hormone treatments were analyzed. A total of 108 R2 R3-MYB transcription factors, named EbMYB1-EbMYB108, were identified from the genome of E. breviscapus. Most of the R2 R3-MYB genes carried 2-4 exons. The phylogenetic tree of MYBs in E. breviscapus and Arabidopsis thaliala was constructed, which classified 234 MYBs into 30 subfamilies. The MYBs in the five MYB subfamilies of A.thaliala were clustered into independent clades, and those in E. breviscapus were clustered into four clades. The transcriptome data showed that MYB genes were differentially expressed in different tissues of E. breviscapus and in response to the treatments with exogenous hormones such as ABA, SA, and GA for different time. The transcription of 13 R2 R3-MYB genes did not change significantly, and the expression patterns of some genes were up-regulated or down-regulated with the extension of hormone treatment time. This study provides a theoretical basis for revealing the mechanisms of R2 R3-MYB transcription factors in regulating the growth and development, stress(hormone) response, and active ingredient accumulation in E. breviscapus.

Clinical effect of an additional maintenance dose of caffeine before ventilator weaning in preterm infants with respiratory distress syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVE@#To study the clinical effect of an additional maintenance dose (5 mg/kg) of caffeine citrate injection at 1 hour before ventilator weaning in improving the success rate of ventilator weaning in preterm infants (gestational age ≤32 weeks) with respiratory distress syndrome (RDS) on mechanical ventilation.@*METHODS@#A total of 338 preterm infants with RDS (gestational age of ≤32 weeks) who were admitted to the Neonatal Intensive Care Unit of Xiamen Maternal and Child Health Hospital from January 2017 to December 2019 and treated with mechanical ventilation were enrolled. They were randomly divided into an observation group and a routine group, with 169 infants in each group. Both groups received early routine treatment with caffeine. The infants in the observation group received an additional maintenance dose of caffeine citrate injection at 1 hour before ventilator weaning. The two groups were compared in terms of reintubation rate and number of apnea episodes within 48 hours after ventilator weaning, changes in blood gas parameters, blood glucose, heart rate, and mean blood pressure at 2 hours after ventilator weaning, and incidence rates of major complications during hospitalization.@*RESULTS@#Compared with the routine group, the observation group had significantly lower reintubation rate (@*CONCLUSIONS@#An additional maintenance dose of caffeine citrate injection at 1 hour before ventilator weaning is safe and effective in improving the success rate of ventilator weaning in preterm infants with RDS and thus holds promise for clinical application.

Analysis and considerations on revision of instructions for traditional Chinese medicine injections / 中国中药杂志

According to the notice on revision of the instructions for traditional Chinese medicine injections(TCMIs) issued by the National Medical Products Administration(NMPA) from January 2006 to May 2020, the revised contents in the instructions for 29 varieties involved in the notice were sorted out, and the existing problems in the instructions for TCMIs were analyzed, so as to provide the basis for dynamic revision of the instructions. It was found that the revised items of instructions for 29 varieties all involved adverse reactions, contraindications and precautions, and warnings were added for 82.76% of 29 TCMIs preparations, indicating that all the revised contents were related to safety issues. In addition, 33.33% of the drugs risks mentioned in the precautions were not indicated in the adverse reactions; 82.76% instructions did not indicate drug interactions; 17.24% instructions lacked medication notes for special populations; 48.28% instructions did not indicate traditional Chinese medicine(TCM) syndromes of the main disease; 44.83% instructions did not indicate the type and stage of indication; and 86.21% instructions did not indicate the course of treatment. It could be concluded that the instructions for TCMIs have known risks of drugs that are not fully reflected in adverse reactions and the effective information is not comprehensive. The risk control measures proposed in the precautions need to have aftereffect evaluation and there is a lack of drug interactions and medications for special populations. As an important part of the full life-cycle management of drugs, the revision of instructions for TCMIs should be continuously improved to provide the basis for safe and reasonable application of TCMIs. Based on the above problems, it is proposed that the marketing license holder as the main body of the revision of instructions should actively carry out post-marketing basic and clinical research in accordance with the characteristics of TCM, combine the updated research with the guidance of TCM theory and improve the revision level of instructions for TCMIs to provide the basis for post-marketing evaluation.

Processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae decoction / 中国中药杂志

On the basis of the previous work of the research group, the orthogonal design method was further used to optimize the processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae Decoction. A total of 9 processed products of T.wilfordii in L.christinae decoction were prepared by four factors and three levels orthogonal design table. The contents of triptolide in T.wilfordii were determined by high performance liquid chromatography(HPLC) before and after processing: 4.27, 3.92, 3.57, 2.75, 2.42, 2.66, 3.51, 1.87, 1.75, 2.03 μg·g~(-1). On this basis, the above processed products were orally given to mice for 28 days. 12 hours after the last administration, food fasting except water was provided, and 24 hours later, the eyeballs were taken for blood and liver tissue. Serum biochemical indexes, liver lipid peroxidation and antioxidant related indexes were detected by kit method. Twenty-eight days after oral administration of raw T.wilfordii, the levels of serum alanine aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and liver malondialdehyde(MDA) in mice increased by 91%(P<0.01), 46%(P<0.05), 73%(P<0.01) and 99%(P<0.01), while the liver antioxidant indexes such as superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GPX) and glutathione-S transferase(GST) significantly decreased(P<0.01). After administration of the processed products, the above indexes were significantly reversed(P<0.01 or P<0.05). Especially, the processing conditions of A_3B_2C_1D_3 had the best detoxification effect on T.wilfordii, which decreased the high levels of AST, ALT, ALP and MDA by 49%(P<0.01), 32%(P<0.01), 42%(P<0.01), and 17%(P<0.05). Therefore, the best processing conditions for T.wilfordii in L.christinae decoction were A_3B_2C_1D_3, namely "15% mass fraction of L.christinae, 1 h moistening time, 160 ℃ frying temperature, and 9 min frying time".

Analysis of Water Adsorption and Thermodynamic Properties of Three Rhei Radix et Rhizoma Decoction Pieces / 中国实验方剂学杂志

Objective:To investigate the moisture adsorption and thermodynamic characteristics of raw products， wine-processed products and fried charcoal products of Rhei Radix et Rhizoma， in order to guide their drying and storage. Method:Static isotherm weighing method was used to determine the adsorption isotherm curves of three Rhei Radix et Rhizoma decoction pieces at 25， 35， 45 ℃， and the test data were fitted with 7 commonly used water adsorption models to determine the best model for studying the adsorption thermodynamic parameters of these decoction pieces. Result:The best adsorption models of these three decoction pieces were all GAB model. At 25， 35， 45 ℃， the absolute safe moisture content of fried charcoal products was 7.43%， 6.79% and 6.20%， of wine-processed products was 8.68%， 8.17% and 7.03%， of raw products was 9.88%， 9.36% and 7.77%， respectively. At 25， 35， 45 ℃， the relative safe moisture content of fried charcoal products was 9.46%， 8.63% and 8.21%， of wine-processed products was 11.49%， 11.03% and 9.74%， of raw products was 13.49%， 12.66% and 11.14%， respectively. The net equivalent heat of adsorption （Qst） and differential entropy （Sd） of these three kinds of decoction pieces all decreased with the increase of equilibrium moisture content， Qst and Sd were in accordance with the entropy-enthalpy complementary theory. The constant velocity temperatures of raw products， wine-processed products and fried charcoal products of Rhei Radix et Rhizoma were 386.66， 391.15， 394.34 K （unit conversion of 1 K=-272.15 ℃）， their Gibbs free energies were 0.372 2， 0.406 0， 0.372 2 kJ·mol-1， respectively. Their adsorption processes were an unspontaneous process driven by enthalpy. Conclusion:The orders of equilibrium moisture content， monomolecular layer moisture content， Qst and Sd of three Rhei Radix et Rhizoma decoction pieces are all raw products>wine-processed products>fried charcoal products. The moisture absorption capacity of the decoction pieces is ranked as raw products>wine-processed products>fried charcoal products. The frying and roasting process significantly affects the hygroscopicity and thermodynamic properties of the three decoction pieces， the reason for this difference may be that the high temperature of the stir-frying results in the decrease of the hygroscopic groups and the increase of the hydrophobic materials in raw products， and the change in the texture of the decoction pieces. The research on the water adsorption characteristics of three Rhei Radix et Rhizoma decoction pieces can provide reference for selecting their storage conditions and drying process.

Development of the Health Promotion Program for the Auxiliary Police based on the PRECEDE Model / 한국직업건강간호학회지

Purpose@#The purpose of this study was to develop of the Health Promotion Program for the Auxiliary Police based on PRECEDE model. @*Methods@#The data were collected from the Auxiliary Police officer in the D provincial Police Agency. The program was developed through analysis of literature review, analysis on the Auxiliary Police’s demand through in-depth interview, and the content validation by an expert group. @*Results@#The program consists group education sessions (7 times, 90 minutes each) for 5 weeks. The program also reflects the concept of quality of life, health promotion behavior, self-efficacy and health knowledge, social support, and availability of resources which are important factors for assessment through PRECEDE. @*Conclusion@#The results may be crucial to develop strategy in order to decrease the disease prevalence as well as increase the participants’ overall quality of life of Auxiliary Police. This is proposed to standardize the Health Promotion Program for the Auxiliary Police.

The Mental Health and Sleep Quality of the Medical Staff at a Hub-Hospital against COVID-19 in South Korea

Objectives@#Now, coronavirus disease (COVID-19) is worldwide threatening. Medical staff’s efforts and sacrifices against COVID-19 are still ongoing. The purpose of this study was to investigate the mental health of the medical staff who have fought against the COVID-19 in hub hospitals. @*Methods@#The medical staff underwent an evaluation of psychiatric and sleep status between March 23rd and April 3rd, 2020. Based on the evaluation, we retrospectively analyzed depression, anxiety, and sleep quality of the medical staff, who worked more than 7 days for fighting against the COVID-19. @*Results@#This study included a total of 101 medical staff. Approximately 1/4 of the medical staff showed depressive mood and low quality of sleep, and more than 1/3 reported anxiety. The nurses reported more severe psychiatric symptoms and poorer sleep quality. @*Conclusions@#This study demonstrated the mental and sleep status of the medical staff against COVID-19. Medical and social support should be considered for them.

Effects of Microbiota on the Treatment of Obesity with the Natural Product Celastrol in Rats

Background@#Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity. @*Methods@#We fed male Sprague-Dawley rats a high-fat diet and administered celastrol to obese rats for 3 weeks. By recording body weight (BW) and other measures, we identified the effective dose of celastrol for obesity treatment. Feces were collected to perform 16S rRNA sequencing, and hypothalami were extracted for transcriptome sequencing. We then treated leptin knockout rats with celastrol and explored the changes in energy metabolism. Male Institute of Cancer Research (ICR) mice were used to test the acute toxicity of celastrol. @*Results@#We observed that celastrol reduced BW and promoted energy expenditure at a dose of 500 μg/kg BW but that food intake was not changed after administration. The diversity of the gut microbiota was improved, with an increased ratio of Bacteroidetes to Firmicutes, and the gut microbiota played an important role in the anti-obesity effects of celastrol. Hypothalamic transcriptome analysis showed a significant enrichment of the leptin signaling pathway, and we found that celastrol significantly enhanced energy expenditure, which was mediated by the leptin signaling pathway. Acute lethal toxicity of celastrol was not observed at doses ranging from 0 to 62.5 mg/kg BW. @*Conclusion@#Our study revealed that celastrol decreased the BW of obese rats by enhancing energy expenditure but not by suppressing food intake and that this effect was mediated by the improvement of the gut microbiota and the activation of the hypothalamic leptin signaling pathway.