Effect of Bufeitang on Lung-gut Axis in Rats with Lung Qi-deficiency Syndrome of Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bufeitang on intestinal flora of rats with lung Qi-deficiency syndrome of chronic obstructive pulmonary disease（COPD）， and to explore the mechanism of traditional Chinese medicine in regulating intestinal flora and thus restoring the balance of lung-gut axis. MethodA total of 84 rats were randomly divided into 7 groups， including blank group， model group， fecal bacterial transplantation（FMT） group， dexamethasone group and low， medium and high dose groups of Bufeitang， 12 rats in each group. Except for the blank group， cigarette and sawdust fumigation combined with intratracheal instillation of lipopolysaccharide（LPS） were used to establish the COPD rat model with lung Qi-deficiency syndrome in all other groups. The low， medium and high dose groups of Bufeitang were intragastric administrated with Bufeitang（3.645， 7.29， 14.58 g·kg-1）， the FMT group was given fecal bacteria liquid enema（10 mL·kg-1）， dexamethasone group was given dexamethasone acetate tablet suspension by gavage（0.135 mg·kg-1）， the blank group and model group were given equal amount of distilled water. Fresh feces were collected after 28 d of continuous intervention for 16S rRNA gene sequencing. Lung and colon tissues were stained with hematoxylin-eosin（HE） for pathomorphological observation， and enzyme-linked immunosorbent assay （ELISA） was performed to detect the contents of tumor necrosis factor-α（TNF-α） and interleukin-8（IL-8） in lung tissues. ResultCompared with the blank group， the model group showed severe abnormal lung tissue structure with alveolar atrophy and collapse accompanied by severe inflammatory cell infiltration. Compared with the model group， the extent of injury was significantly improved， and inflammatory cell infiltration was reduced with basically normal alveolar structure in the high dose group of Bufeitang. Compared with the blank group， the model group had severely abnormal colonic tissue structure， the epithelial cells in the mucosal layer were eroded and shed， the number of inflammatory cells increased， the submucosal layer was edematous and the gap was enlarged. Compared with the model group， the extent of damage was significantly improved in the medium and high dose groups of Bufeitang， the epithelial cells in the mucosal layer were neatly and closely arranged， with only a small amount of inflammatory cell infiltration and no significant degeneration. Compared with the blank group， the TNF-α and IL-8 levels of lung tissue in the model group were significantly increased（P<0.01）. Compared with the model group， the TNF-α and IL-8 levels of lung tissues in the low， medium and high dose groups of Bufeitang were significantly decreased（P<0.01）. Bufeitang significantly modulated the number of bacteria species as well as alpha and beta diversity of model rats， corrected the return of intestinal flora to normal abundance and diversity， and positively regulated 4 differential phyla（such as Firmicutes， Proteobacteria） and 13 differential genera（such as Turicibacter， Lactobacillus， Anaerobiospirillum， Intestinimonas） in COPD model rats with lung Qi-deficiency syndrome， and down-regulated 2 carbohydrate metabolic pathway functions， including the pentose phosphate pathway（non-oxidative branch） Ⅰ and the Calvin-Benson-Bassham cycle. ConclusionBufeitang can modulate the abundance and diversity of intestinal flora species， affect the function of metabolic pathways， repair the structure of lung and colon tissues， regulate the level of inflammatory factors， and thus improve COPD with lung Qi-deficiency syndrome. The mechanism may be related to its regulation of inflammation-related intestinal flora to restore the balance of lung-gut axis in COPD with lung Qi-deficiency syndrome.

A quantitative study of airway ultrasound in predicting difficult laryngoscopy: A prospective study / 中华创伤杂志(英文版)

PURPOSE@#As common clinical screening tests cannot effectively predict a difficult airway, and unanticipated difficult laryngoscopy remains a challenge for physicians. We herein used ultrasound to develop some point-of-care predictors for difficult laryngoscopy.@*METHODS@#This prospective observational study included 502 patients who underwent laryngoscopy and a detailed sonographic assessment. Patients under 18 years old, or with maxillofacial deformities or fractures, limited mouth opening, limited neck movement or history of neck surgery were excluded from the study. Laryngoscopic views of all patients were scored and grouping using the modified Cormack-Lehane (CL) scoring system. The measurements acquired comprised tongue width, the longitudinal cross-sectional area of the tongue, tongue volume, the mandible-hyoid bone distance, the hyoid bone-glottis distance, the mandible-hyoid bone-glottis angle, the skin-thyrohyoid membrane distance, the glottis-superior edge of the thyroid cartilage distance (DGTC), the skin-hyoid bone distance, and the epiglottis midway-skin distance. ANOVA and Chi-square were used to compare differences between groups. Logistic regression was used to identify risk factors for difficult laryngoscopy and it was visualized by receiver operating characteristic curves and nomogram. R version 3.6.3 and SPSS version 26.0 were used for statistical analyses.@*RESULTS@#Difficult laryngoscopy was indicated in 49 patients (CL grade Ⅲ - Ⅳ) and easy laryngoscopy in 453 patients (CL grade Ⅰ - Ⅱ). The ultrasound-measured mandible-hyoid bone-glottis angle and DGTC significantly differed between the 2 groups (p < 0.001). Difficult laryngoscopy was predicted by an area under the curve (AUC) of 0.930 with a threshold mandible-hyoid bone-glottis angle of 125.5° and by an AUC of 0.722 with a threshold DGTC of 1.22 cm. The longitudinal cross-sectional area of the tongue, tongue width, tongue volume, the mandible-hyoid distance, and the hyoid-glottis distance did not significantly differ between the groups.@*CONCLUSION@#Difficult laryngoscopy may be anticipated in patients in whom the mandible-hyoid bone-glottis angle is smaller than 125.5° or DGTC is larger than 1.22 cm.

A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent / 中国当代儿科杂志

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.

Research Progress in Antibody Responses Against SARS-CoV-2 Variants of Concern / 中国医学科学院学报

So far,the coronavirus disease 2019(COVID-19)has been persisting for nearly three years,infecting about 700 million people and causing more than 6 million deaths,which has seriously affected the human society.According to Global Initiative on Sharing All Influenza Data,there are more than 12 million SARS-CoV-2 variants,of which the five major variants of concern are Alpha,Beta,Gamma,Delta and Omicron.Their infectivity,pathogencity,and neutralization resistance have changed greatly compared with the original strain,which has brought great pressure to the prevention and control of the pandemic.Antibody level testing is critical for confirming infection,epidemiological investigation,vaccine development,and neutralizing drug preparation.Focusing on the humoral immunity against SARS-CoV-2,this paper introduces the mutation sites,neutralization resistance,and vaccination efficacy of the five variants of concern,and briefly summarizes the evolutionary characteristics,future mutation directions,and host immunity.

Current status of atezolizumab combined with bevacizumab in the treatment of hepatocellular carcinoma / 中华肝胆外科杂志

Hepatocellular carcinoma (HCC) has a hidden onset and rapid progress. Most of the patients have lost the opportunity of surgery at the onset, and the systemic treatment effect is not satisfactory. In recent years, immune checkpoint inhibitors combined with targeted therapy have brought hope to HCC patients. In particular, treatment with atezolizumab combined with bevacizumab has been recommended by many domestic and foreign guidelines as the first-line treatment for patients with unresectable HCC who have not previously received systematic treatment. In this review, the application status of atezolizumab plus bevacizumab, coping strategies for treatment failure, cost-benefit analysis and side effects were described in order to provide reference for clinical treatment.

Tanshinone IIa attenuates vascular calcification through inhibition of NF-κB and β-catenin signaling pathways / 生理学报

Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and β-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and β-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and β-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.

Study on mechanisms of Th17/Treg imbalance in patients with cystic echinococcosis based on miRNA expression profiles / 中国血吸虫病防治杂志

OBJECTIVE@#To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis.@*METHODS@#Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched.@*RESULTS@#A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways.@*CONCLUSIONS@#Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.

The role of TNF-α/TNFR1 inhibiting autophagy of M1-type Kupffer cells in liver injury in trichloroethylene-sensitized mice / 中华劳动卫生职业病杂志

Objective: To detect the expression levels of M1-type polarization and autophagy-related indicators in the liver of trichloroethylene (TCE) -sensitized mice, and to explore the role of liver tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1) in regulating M1-type Kupffer cells autophagy in liver injury in TCE-sensitized mice. Methods: In November 2019, according to simple random grouping, 45 SPF grade BALB/c female mice (6-8 weeks old) were divided into 4 groups: blank control group (n=5) , solvent control group (n=5) , TCE treatment group (n=18) , TCE+R7050 (inhibitor) treatment group (n=17) . Transdermally sensitized mice, 24 h after the last challenge, the mice were divided into TCE sensitized group and TCE non-sensitized group according to the skin reaction score. The livers of mice were harvested, and the pathological changes of the livers were observed under light and electron microscopes. Western blotting was used to detect the expressions of TNF-α, TNFR1 and autophagy-related indexes. The expression of inducible nitric oxide synthase (iNOS) , a marker of M1-type Kupffer cells, was detected by immunohistochemistry, and the occurrence of autophagy in M1-type Kupffer cells was detected by immunofluorescence double-labeling method. Results: The sensitization rate of TCE treatment group was 38.9% (7/18) , and TCE+R7050 treatment group was 35.3% (6/17) , with no significant difference between the two groups (P=1.000) . Compared with the blank control group, mice in the TCE sensitized group had abnormal liver ocytes, obvious liver injury, reduced mitochondria and broken endoplasmic reticulum. Western blotting results showed that the expressions of TNF-α and TNFR1 protein in the liver of the mice in the TCE sensitized group increased, the expression of iNOS protein in M1-type Kupffer cells increased, and the expressions of autophagic microtubule-associated protein 1 light-chain 3 (LC3B) and Beclin1 protein were decreased (P<0.05) . The results of immunohistochemistry showed that iNOS was not significantly expressed in the blank control group and solvent control group, and a small amount of expression was found in the TCE non-sensitized group, the positive staining area was obvious in TCE sensitized group, and the expression of iNOS was significantly increased (P<0.05) . Immunofluorescence results showed that the iNOS protein levels in the blank control group, solvent control group and TCE non-sensitized group were lower, and only partially colocalized with P62; the colocalization of iNOS with P62 in the TCE sensitized group was significantly increased. Conclusion: TNF-α/TNFR1 signaling pathway may promote liver injury in TCE-sensitized mice by inhibiting autophagy of M1-type Kupffer cells.

The role of ROS/TXNIP/NLRP3 pathway in the skin injury of trichloroethylene sensitized mice / 中华劳动卫生职业病杂志

Objective: To explore the mechanism of reactive oxygen species/thioredoxin-interacting protein/nucleotide-binding oligomerization domain-like receptor 3 (ROS/TXNIP/NLRP3) pathway in the skin injury of trichloroethylene (TCE) sensitized mice. Methods: In August 2020, 40 female BALB/c mice were randomly divided into control group (n=5) , solvent control group (n=5) , TCE treatment group (n=15) and TCE+(2-(2, 2, 6, 6-Tetrameyhylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito TEMPO) treatment group (n=15) . The TCE sensitization model was established. Mice in the TCE treatment group and TCE+Mito TEMPO treatment group were divided into the sensitized positive group and the sensitized negative group according to the skin erythema and edema reactions on the back of the mice 24 h after the last stimulation. The mice were sacrificed 72 h after the last stimulation, the back skin of the mice was taken, and the skin lesions were observed. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3, and the Western Blot was performed to detect the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) , cysteinyl aspartate specific proteinase 1 (Caspase 1) , Interleukin-1β (IL-1β) and TXNIP proteins in the skin of the mice, the reactive oxygen species (ROS) kit was used to detect the level of intracellular ROS in the back skin tissue. Results: The sensitization rates of TCE treatment group and TCE+Mito TEMPO treatment group were 40.0% (6/15) and 33.3% (5/15) , respectively, and there was no significant difference between the two groups (P>0.05) . The back skin of the mice in the TCE sensitized positive group was thickened and infiltrated by a large number of inflammatory cells. The number of mitochondria in the epidermis cells was significantly reduced, the mitochondrial crest disappeared and vacuolar degeneration occurred. TCE+Mito TEMPO sensitized positive group had less damage, more mitochondria and relatively normal cell structure. Compared with the solvent control group and corresponding sensitized negative groups, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE sensitized positive group and TCE+Mito TEMPO sensitized positive group were significantly increased (P<0.05) . Compared with TCE sensitized positive group, the expression levels of NLRP3, ASC, Caspase 1, IL-1β, TXNIP proteins and the content of ROS in the TCE+Mito TEMPO sensitized positive group were significantly decreased (P<0.05) . Conclusion: ROS/TXNIP/NLRP3 pathway was activated and then encouraged the release of IL-1β, finally aggravated the TCE-induced skin injury.

Traditional Chinese Medicine Intervention on Th17/Treg Balance in Chronic Obstructive Pulmonary Disease： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD）， a common clinical chronic respiratory disease， has a long course and is intractable. It is closely related to many factors， such as immune imbalance. Helper T cell 17 （Th17）， an immune-promoting cell， and regulatory T cell （Treg）， an immunosuppressive cell， maintain the balance of the immune microenvironment together. In the course of COPD， the proportion of Th17 cells usually increases， while the proportion of Tregs that inhibit Th17 activity decreases. Their coordination and balance are critical in the inflammatory and immune processes of COPD. At present， COPD is mainly treated with nasal inhalation preparations and oral drugs by western medicine. In spite of a certain therapeutic effect， side effects of drugs and heavy economic burden are becoming increasingly prominent. Modern research shows that traditional Chinese medicine （TCM） has the characteristics of few side effects， stable curative effect， and multi-target regulation， and it is advantageous and promising in the prevention and treatment of COPD. In recent years， a large number of TCM clinical and experimental trials on the intervention of Th17/Treg balance in COPD have been launched. Substantial pieces of evidence confirm that the intervention of Th17/Treg balance is an important potential target of TCM in the treatment of COPD. This study reviewed the previous research on the intervention effect of single Chinese medicine， effective components of Chinese medicine， and Chinese medicinal compound on Th17/Treg balance in COPD to comprehensively reveal the potential target of Th17/Treg balance in COPD for clinicians and scientific researchers， promote relevant research， and provide references for the rational application of TCM in the prevention and treatment of COPD.

Study of clinical manifestations and outcomes of 14 newborns with primary immunodeficiency disease / 中国小儿急救医学

Objective:To explore the clinical manifestations, genetic disorder, prognosis of 14 neonates with primary immunodeficiency disease(PID).Methods:A total of 14 newborns with PID admitted to Department of Neonatology at Beijing Children′s Hospital from January 2017 to December 2019 were enrolled for retrospective analysis, focusing on their clinical manifestation, peripheral blood cell examnations, gene mutation, and outcomes after hemotopoietic stem cell transplantation(HSCT).Results:The average gestational age of the newborn was (38.6±1.2) weeks, the birth weight was (3 265±325)g, and the median diagnosis time was 57.5 days.Fourteen newborns with PID were diagnosed by whole exome sequencing as chronic granuloma (6/14), DiGeogre syndrome (3/14), Wiskott-Aldrich syndrome (2/14), severe combined immunodeficiency (2/14) and selective IgA deficiency (1/14). Regarding the clinical manifestations, fever, pneumounia and colitis accounted for 7/14, the decrease of T lymphocytes in peripheral blood accounted for 6/14, and the decrease of B lymphocytes accounted for 5/14.The absolute value of eosinophils increased (>500 cells/mm 3) accounted for 12/14, of which moderately increased (1 500 to 5 000 cells/mm 3) accounted for 5/12, and the absolute value of monocytes increased (median>1.5×10 9/L) accounted for 7/14.Follow-up children received HSCT accounted for 7/14, and the median time of receiving transplantation was 330 days after birth.By the time of follow-up, the primary disease resolved after HSCT accounted for 5/7, and the survival rate was 85.7%.Among them, two children with chronic granulomatosis were diagnosed with inflammatory bowel disease before transplantation, and the primary disease improved after HSCT.Three-quarters of the deaths had inflammatory bowel disease-like manifestations and died of infectious shock. Conclusion:The clinical manifestations of children with PID during the neonatal period are not specific.The manifestations of colitis need more attention.Some of the newborns with PID will evolve into inflammatory bowel disease or have inflammatory bowel disease-like manifestations or even die of it.HSCT is a fundamental treatment for the primary disease.

Effect of compound nutrients on behavior and fatigue in mice with high temperature exercise / 中国职业医学

OBJECTIVE: To explore the effects of high temperature on learning and memory ability, behavioral activity, and fatigue as well as the intervention effect of compound nutrients on the exercising mice. METHODS: Thirty specific pathogen-free healthy male Kunming mice were randomly divided into the normal-temperature exercise, high-temperature exercise, and high-temperature exercise supplement groups, with 10 mice in each group. The mice in these three groups performed treadmill exercise for one hour every day, six days per week, and continued for four weeks. The mice in the high-temperature exercise supplement group were fed with 0.3 mL of compound nutrients 30 minutes before each treadmill exercise, whereas the mice in the normal-temperature exercise and the high-temperature exercise groups were fed with an equal volume of distilled water. At the end of the treadmill exercise, the mice were subjected to experiments on their neurological behaviors. The serum of mice in each group were collected to detect the lactic acid level, urea nitrogen level, and creatine kinase activity. The liver and gastrocnemius muscle tissues were then taken for detecting the levels of liver glycogen and muscle glycogen.RESULTS: Compared with the mice in the normal-temperature exercise group, the escape latency of the mice in the high-temperature exercise group was prolonged(P<0.05), whereas the number of platform crossings, percentage of target quadrant time, and distance were reduced(all P<0.05). Compared with the mice in the high-temperature exercise group, the escape latency of the mice in the high-temperature exercise supplement group was shortened(P<0.05), whereas the number of platform crossings, percentage of target quadrant time, and distance were increased(all P<0.05). Compared with the mice in the normal-temperature exercise group, the first fall time and grip strength of the mice in the high-temperature exercise group were reduced(all P<0.05), whereas the number of falls was increased(P<0.05). Compared with the mice in the high-temperature exercise group, the first fall time and grip strength of the mice in the high-temperature exercise supplement group were increased(all P<0.05), whereas the number of falls was reduced(P<0.05). Compared with the mice in the normal-temperature exercise group, the serum lactic acid level, urea nitrogen level, and creatine kinase activity of the mice in the high-temperature exercise group were increased(all P<0.05), whereas the levels of liver glycogen and muscle glycogen were decreased(all P<0.05). Compared with the mice in the high-temperature exercise group, the serum lactic acid level, urea nitrogen level, and creatine kinase activity of the mice in the high-temperature exercise supplement group were decreased(all P<0.05), whereas the levels of liver glycogen and muscle glycogen were increased(all P<0.05). CONCLUSION: High temperature exercise can lead to decreased learning and memory ability and behavioral activity in mice, resulting in exercise-induced fatigue. Supplemental compound nutrients can prevent these changes.

Protective effects of proanthocyanidins from Rubus amabilis Focke on pancreatic tissues of diabetic mice / 中国药理学通报

Aim To study the protective effect of proanthocyanidins extracted from Rubus amabilis Focke (RPC) on the pancreatic tissues of diabetic mice and the underlying mechanism. Methods C57BL/6 male mice were given a high-sugar and high-fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. The mice whose FBG were higher than 16. 7 mmol · L

Study on treatment of "cytokine storm" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway / 中国中药杂志

Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to "cytokine storm". "Cytokine storm" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the "cytokine storm". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on "cytokine storm" according to the potential herbs in the "National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)". The results showed that the hit components with the inhibitory effect on AA were magnolignan Ⅰ, lonicerin and physcion-8-O-β-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.

Study on screening potential traditional Chinese medicines against 2019-nCoV based on Mpro and PLP / 中国中药杂志

With the rapid outbreak of COVID-19, traditional Chinese medicine(TCM) has been playing an active role against the epidemic. However, the screening of TCM is limited by the development cycle and laboratory conditions, which greatly limits the screening speed. This study established optimization docking models and virtual screening to discovery potential active herbs for the prevention and treatment of the novel coronavirus based on molecular docking technology. The crystal structures of 3 CL protease(Mpro) and papain-like protease(PLP) were obtained from PDB database and homologous modeling respectively, and were used to conduct virtual screening of TCMD 2009 database by CDOCKER program. The ingredients scored in the top 100 were selected respectively, and the candidate herbs were ranked by the numbers of hit molecules. Based on Mpro inhibitors screening, 12 322 potential active components were obtained, and the representative active components included aster pentapeptide A, ligustrazine, salvianolic acid B, etc., and Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Notoginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Dianthi Herba, Rhei Radix et Rhizoma, Cistanches Herba were obtained. While 11 294 potential active ingredients were obtained by PLP inhibitor screening, representative active ingredients included gingerketophenol, ginkgol alcohol, ferulic acid, etc., and Codonopsis Radix, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, Ginkgo Semen, Chuanxiong Rhizoma, Trichosanthis Fructus, Paeoniae Radix Alba, Psoraleae Fructus, Sophorae Flavescentis Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix were chosen. By combining the diagnosis and treatment scheme of Hunan province's and angiotensin converting enzyme 2(ACE2) inhibitors screening from literature, present study also discussed the rational application of candidate herbs to this epidemic situation. Trichosanthis Fructus obtained by PLP inhibitors screening and Fritillaria verticillata obtained by ACE2 inhibitors screening were parts of the Sangbei Zhisou Powder and Xiaoxianxiong Decoction, which might be applicable to the syndromes of cough and dyspnea. Rhei Radix et Rhizoma screened by Mpro and Trichosanthis Fructus screened by PLP were contained in Maxing Shigan Decoction and Xuanbai Chengqi Decoction, and could be applied to the syndromes of epidemic virus blocking lung. Mori Folium, Lonicerae Japonicae Flos and Forsythiae Fructus obtained by ACE2 inhibitors screening were included in the Sangju Decoction and Yinqiaosan, which might be applicable to the syndromes of warm pathogen attacking lung and cough and dyspnea. The results of this study are intended to provide a reference for the further development of traditional Chinese medicine to deal with the new epidemic.

Cryo-EM structure of an early precursor of large ribosomal subunit reveals a half-assembled intermediate

Assembly of eukaryotic ribosome is a complicated and dynamic process that involves a series of intermediates. It is unknown how the highly intertwined structure of 60S large ribosomal subunits is established. Here, we report the structure of an early nucleolar pre-60S ribosome determined by cryo-electron microscopy at 3.7 Å resolution, revealing a half-assembled subunit. Domains I, II and VI of 25S/5.8S rRNA pack tightly into a native-like substructure, but domains III, IV and V are not assembled. The structure contains 12 assembly factors and 19 ribosomal proteins, many of which are required for early processing of large subunit rRNA. The Brx1-Ebp2 complex would interfere with the assembly of domains IV and V. Rpf1, Mak16, Nsa1 and Rrp1 form a cluster that consolidates the joining of domains I and II. Our structure reveals a key intermediate on the path to establishing the global architecture of 60S subunits.

The effects of hypoxia on the expression of inflammatory factor high mobility group box-1 in the pulmonary arteriolae of neonatal SD rats / 中国新生儿科杂志

Objective To study the effects of hypoxia on the expression of inflammatory factor high mobility group box-l(HMGB1) in the pulmonary arteriolae of neonatal SD rats.Method A total of 80 neonatal SD rats were randomly assigned into control group and hypoxia-induced persistent pulmonary hypertension of the newborn model (PPHN) group.The PPHN group was subdivided into 2 h,8 h,24 h,and 3 d post-PPHN subgroups according to the time of sacrifice.PPHN model was established on postnatal day 4 when rat pups in PPHN group were kept in low-oxygen box (10％ O2 and 90％ N2) for consecutively 7 days.Multi-channel physiological transducer RM-6280 was used recording the mean pulmonary artery pressure (mPAP) at the root to pulmonary artery of rat pups.ELISA method was used examining the serum level of HMGB1 of rat pups in each group.The pathology of the lung tissue was studied using optical microscope after HE staining,and MIAS-2000 medical image analysis software was used to calculate the ratio of the middle membrane thickness to the outer diameter of the pulmonary arteriolae wall (MT％).Protein level of HMGB1 in the lung was examined using Western Blot.Result The lung pathology in PPHN rats showed thickening of the middle membrane of the pulmonary arteriolae wall and stenosis of the pulmonary arteriolae.MT％ of control group and PPHN group were 5.3％ (3.7％,7.6％) and 7.1％ (4.6％,9.2％),respectively,without significant differences (P＞0.05).At 2 h,8 h,24 h,3 d post-PPHN timepoints,the serum levels of HMGB1 in PPHN group were (13.2±3.1),(15.4±3.6),(17.1±3.5),and (15.8±3.6) ng/ml,respectively,without intra-subgroup differences (F=2.134,P＞0.05),but significant differences existed when compared with control group at each timepoint (P＜0.01).Western Blot showed that HMGB1 protein expression in the lungs were significantly elevated soon after PPHN,peaked at 8～24 h,and reduced but still significantly elevated at 3 d after PPHN comparing with normal control.Significant differences existed at 2 h,8 h,and 24 h timepoints (P＜0.01,respectively).The HMGB1 protein of PPHN group declined significantly at 3 d timepoint without significant differences comparing with the control group (P＞0.05).Conclusion HMGB1 is closely related with the pathogenesis of PPHN,indicating the inflammatory response plays an important role in the mechanisms of PPHN.HMGB1 may be an indicator for the assessment of hypoxia-induced PPHN.

Preparetion and analysis on the immunogenicity of Echinococcus granulosus-specific diagnostic antigen Eg-07279 / 中国人兽共患病学报

We screened echinococcosis-specific diagnostic antigen and verified its immunogenicity.The sequencing data of Echinococcus granulosus released by the National Human Genome Research Center was analyzed.The bioinformaties method was used to screen out Eg-07279 antigen gene Eg-07279,which was not expressed in Echinococcus granulosus and highly expressed in the original metacercariae.After expression,the recombinant protein rEg-07279 was purified by affinity chromatography.The specific IgG level was detected in the recombinant protein immunized mice and the immunogenicity was verified by Western blot.The selected antigen molecule Eg-07279 was cloned,expressed and purified to obtain the recombinant protein.The results of ELISA showed that the specific IgG level of Eg-07279 (2.559±0.125) was significantly higher than that of the blank group (0.319 0±0.01),the difference was statistically significant (P＜0.01);the Western blot results showed that the recombinant plasmids could be recognized by the secondary infection of the protoscolex and the serum of the recombinant protein immunized group,while the serum of the blank control group was not recognized by the serum.In summary,the Eg07279 antigen of E.granulosus was obtained and it was proved that the recombinant protein has good immunogenicity and is a good diagnostic antigen candidate molecule.

The amplitude integrated electroencephalogram feature of term newborns with different blood glucose level / 中国新生儿科杂志

Objective To study the characteristics of amplitude integrated electroencephalogram (aEEG) in full-term newborns with different blood glucose levels,so as to provide clinical evidence for assessing brain function after hypoglycemia.Method Full-term neonates admitted to the neonatal ward of the Third Xiangya Hospital of Central South University from June 2014 to May 2016 with the initial diagnosis of hypoglycemia were enrolled to hypoglycemia group.According to the lowest level of blood glucose,infants were assigned to three subgroups,severe hypoglycemia group (＜ 1.1 mmol/L),moderate hypoglycemia group (1.1 ～ ＜2.2 mmol/L),and mild hypoglycemia group (2.2 ～ ＜2.8 mmol/L).Time matched asymptomatic term infants,who were admitted to the neonatal ward due to maternal high risks and with normal blood glucose after birth,were enrolled to control group.A 4 h continuous aEEG monitoring was completed for each infant in hypoglycemia group within 12 h after the blood glucose level stabilized.The newborns in control group were given aEEG examination 72 ～ 120 h after birth,the duration of monitoring was also 4 h.The aEEG scoring was completed and compared by rank sum test.Result A total of 83 neonates were enrolled in hypoglycemia group,including 11 with severe hypoglycemia,32 with moderate hypoglycemia,and 40 with mild hypoglycemia.Another 26 neonates with normal blood glucose level were enrolled in control group.The incidence of pregnancy-induced maternal blood glucose elevation was statistically significant among each group (P ＜ 0.05).The duration of neonatal hypoglycemia in severe hypoglycemia group was longer than that in moderate hypoglycemia group and mild hypoglycemia group [38.3 (20.7,50.4) h vs.20.4(15.3,22.6) h,13.7 (7.8,19.4) h] (P＜ 0.05).The range of glucose level in severe hypoglycemia group was larger than that in mild and moderate hypoglycemia group [5.0 (4.0,5.5) mmol/Lvs.3.5 (3.0,3.9) mmol/L,3.3 (2.8,3.8) mmol/L] (P ＜ 0.05),but there was no significant difference in the onset of first hypoglycemia between groups (P ＞ 0.05).The aEEG score showed that there was significant difference in total score and sleep-wake cycle score between groups (P ＜ 0.05).The score of sleep-wake cycle in severe hypoglycemia group was significantly lower than that in moderate hypoglycemia group or in mild hypoglycemia group or in the control group (P ＜ 0.05),while there was no significant difference between moderate and mild hypoglycemia groups,and between moderate hypoglycemia and control group (P ＞ 0.05).Conclusion Severe hypoglycemia can lead to neonatal aEEG changes,mainly in the sleep-wake cycle changes.

Development of methods for separation and analysis of triacylglycerols / 中国药学杂志

As one kind of lipid excipients, triacylglycerols (TAGs) are being more and more widely used in pharmaceutics with the development of advanced drug delivery systems. As their characteristics are mainly determined by their structures and compositions, strict quality control ought to be performed on TAGs, in order to guide their use in pharmaceutics. However, because of their complex compositions, no qualtity standard is set for TAGs in Ch.P currently. In this paper, we reviewed the methods for the separation and analysis of TAGs, includingthin-layer chromatog raphy, solid-phase extraction, gas chromotography, liquid chromatography, two-dimensional liquid chromatography, and ultraperformance convergence chromatography, and summarized their advantages and disadvantages. The application scope of each method was also overviewed in this review. Besides that we also pointed outthat according to our own study the newly emerged ultraperformance convergence chromatography would be one of the best methods to analyze TAGs.