The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-κB signaling pathway / 药学学报

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease / 中华儿科杂志

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.@*METHODS@#Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.@*RESULTS@#The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01).@*CONCLUSION@#The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma / 中华肿瘤杂志

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

Preparation, in vitro characterization and pharmacokinetics of paclitaxel thermosensitive gel / 药学学报

Local drug delivery is a new strategy to prevent postoperative recurrence of cancer, thermosensitive gel is a typical topical drug delivery system. In this study, a novel paclitaxel thermosensitive gel (PTG) was prepared to prevent recurrence after chemotherapy for cancer, the effects of drug particle size on release and absorption rate in vivo were investigated. Paclitaxel suspensions with different particle sizes were prepared by medium grinding, high pressure homogenization, air crushing and screening. Using poloxamer as the gel matrix and carbomer as the biological adhesive, Box-Behnen was used to optimize the formulation of PTG. The morphology, viscosity, rheological properties and biological adhesion of thermosensitive gel were characterized. The relationship between dissolution and release of thermosensitive gel was investigated by weight loss method, pharmacokinetics was studied in rats. The paclitaxel suspensions with the particle sizes of 350 nm, 800 nm, 3 μm and 9 μm were prepared, 19% poloxamer 407, 4% poloxamer 188 and 0.1% carbomer were used to prepare PTG. The phase transition temperature of thermosensitive gel was 30 to 35 ℃, there was a good linear relationship between in vitro release and gel dissolution. In the pharmacokinetic study, area under the curve (AUC0-t) increased with the decrease of particle size. In general, the PTG prepared in this study can rapidly change into gel under human body temperature, provided with good adhesion. The release rate in vitro is closely related to the particle size, the release rate increased with the decrease of particle size. This study provides data support for preventing postoperative recurrence of cancer. The animal welfare and experimental process in this paper follow the regulations of the Animal Ethics Committee of the Academy of Military Medical Sciences.

Based on clinical application research progress of thermosensitive gel in different drug delivery sites / 药学学报

The advantages of local administration are as follow: release drugs directly at the lesion, increase the drug concentration in lesion location and reduce the side effects of systemic administration. Thermosensitive gel is one of typical local administration agents. It exhibits the different physical characteristics with the change of temperature. It is sol-gel at low temperature or storage temperature, while when the temperature rises to the transition temperature or near the body temperature, it is semisolid gel with a certain viscoelasticity, and can recover rapidly. It can enhance the local adhesion, which prolongs the local retention time of drugs. As a result, thermosensitive gel can control and display the release of drugs, which can significantly improve the bioavailability of drugs. This review summarizes the characteristics of thermosensitive gel, thermosensitive materials, and its application in different parts: nasal cavity, eye, vagina, periodontal, skin, tumor and joint cavity, based on clinical needs.

Advance in Point-of-care Ultrasound for Pulmonary Rehabilitation in Critically Ill Patients (review) / 中国康复理论与实践

In addition to primary diseases, critically ill patients often suffered from multiple functional disorders, including pulmonary dysfunction. Pulmonary rehabilitation can effectively improve the lung and overall function of patients, which need assistance of relevant examinations. Point-of-care ultrasound (POCUS) can not only help to diagnose, evaluate, monitor and treat the disease faster, more accurate and safer, but also reduce the adverse events resulting from handling, activities and radiation, which is applied more extensively in critical patients accepting pulmonary rehabilitation.

The Expression of WTAP Gene in Acute Myeloid Leukemia and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of WTAP gene in acute myeloid leukemia (AML) and its clinical significance.@*METHODS@#74 acute myeloid leukemia patients with non-M3 type and 19 normal donors were selected, and real-time quantitative polymerase chain reaction was used to detect the mRNA expression level of WTAP gene in their bone marrow cells. The relationship between the mRNA expression level of WTAP gene and the clinical characteristics was analyzed.@*RESULTS@#The relative mRNA expression of WTAP gene in the non-M3 AML group was significantly higher than that in the healthy control group, and the difference showed statistically significant (P0.05) according to the classification of FAB. The mRNA expression level of WTAP gene in FLT3-ITD mutated AML patients was higher than that in FLT3-ITD unmutated group (P=0.016), and the mRNA expression level of WTAP gene in AML patients with CEBPα mutation was lower than that in CEBPα unmutated group (P=0.016). The expression level of WTAP mRNA was positively correlated with WT1 expression (r=0.6866, P0.05). The expression level of WTAP mRNA showed no obvious effect on the complete remission of patients after first treatment. The different expression level of WTAP gene at initial diagnosis showed also no effect on the overall survival time of patients.@*CONCLUSION@#The expression level of WTAP gene is increasing in new diagnosed non-M3 acute myeloid leukemia. There is a positive correlation between the expression level of WTAP gene and the expression level of WT1 fusion gene. WTAP mRNA always shows higher expression in patients with FLT3-ITD mutation than that in patients without FLT3-ITD mutation, and shows lower expression in patients with CEBPα mutation than that in unmutated group.

Comparison of Plasma Components between Frozen Plasma and Fresh Frozen Plasma / 中国实验血液学杂志

OBJECTIVE@#To compare the plasma components of frozen plasma (FP) and fresh frozen plasma (FFP).@*METHODS@#Twenty samples of FP and 20 samples of FFP from Beijing Red Cross Blood Center were randomly selected. Immediately after plasma melting, 12 plasma components including coagulation factor, fibrinolytic system and anticoagulation protein were detected, including activated partial thromboplastin time (APTT), prothrombin time (PT), coagulation factor Ⅷ (FⅧ) activity, coagulation factor Ⅴ (FⅤ) activity, fibrinogen(FIB) level, ADAMTS-13 activity, von Willebrand factor(vWF) activity, D-dimer (D-dimer, DD), fibrin degradation products (FDP), antithrombin (AT), protein C (PC), and protein S (PS). All these coagulation components between the two types of plasma were compared and analyzed.@*RESULTS@#Compared with FFP, APTT in FP was significantly prolonged(t=3.428, P0.05).@*CONCLUSION@#FP can substitute FFP in the treatment of some diseases, although it is lack of some coagulation factors and anticoagulation protein.

Clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).@*METHODS@#A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis.@*RESULTS@#Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×10@*CONCLUSIONS@#Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.

Chinese herbal medicine resources: Where we stand / 中草药·英文版

In recent years, the development of Chinese herbal medicine (CHM) has been challenged by shortages of CHM resources and drug safety concerns related to end products. There have been significant efforts by Chinese scholars to tackle these challenges, which are revealed by analyzing the research trend of CHM resources via surveying Chinese Traditional and Herbal Drugs (Zhong Cao Yao), a representative journal in CHM. Our study focused on 781 articles in CHM resources from 2013 to 2018 and included four subject areas: germplasm resources, quality analysis and evaluation, cultivation, and bioengineering of CHM. Discussion and prospective for future investigations were also presented, including: construct the core germplasm of medicinal plants and expand germplasms; combine molecular research with field experiments and promote the deeper study of cultivation of CHM plants; improve the quality evaluation method of CHM and strengthen the identification of Chinese patented medicines; promote the sustainable development of CHM resources by utilizing bioengineering and synthetic biology. This study helps international scholars understand the status quo of CHM research and provides theoretical support for the healthy, modern, and international development of CHM, and it will facilitate the sustainable development of the traditional Chinese medicine industry.

Pharyngeal Electrical Stimulation for Post-stroke Dysphagia: A Meta-analysis / 中国康复理论与实践

Objective:To evaluate the effect of pharyngeal electrical stimulation (PES) on post-stroke dysphagia. Methods:Randomized controlled trial (RCT) about pharyngeal electrical stimulation for dysphagia after stroke were searched in Coehrane Library, Embase, EBSCO, PubMed, Web of Science, CBM, VIP, CNKI and Wanfang Data until June, 2020. The literature quality was evaluated, and the data were analyzed with RevMan 5.3. Results:Five RCTs were returned, including 325 patients. PES was more effective in improvement of Dysphagia Severity Rating Scale scores (SMD = -0.27, 95%CI -0.53 to -0.01, P = 0.04) and decannulation rate (RR = 4.69, 95%CI 2.02 to 10.87, P < 0.001); however, there was no significant difference in Functional Oral Intake Scale scores (SMD = 0.24, 95%CI -0.32 to 0.79, P = 0.40), Penetration-Aspiration Scale scores (MD = -0.18, 95%CI -0.74 to 0.39, P = 0.54) and length of stay (SMD = -0.16, 95%CI -0.42 to 0.11, P = 0.25) between PES and control. Conclusion:Pharyngeal electrical stimulation can improve the swallowing function and enhance decannulation rate for post-stroke dysphagia, while it is uncertain for functional oral intake, risk of aspiration and length of stay.

Genome-wide identification and analysis of AP2/ERF transcription factors related to camptothecin biosynthesis in Camptotheca acuminata / 中国天然药物

Camptotheca acuminata produces camptothecin (CPT), a monoterpene indole alkaloid (MIA) that is widely used in the treatment of lung, colorectal, cervical, and ovarian cancers. Its biosynthesis pathway has attracted significant attention, but the regulation of CPT biosynthesis by the APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors (TFs) remains unclear. In this study, a systematic analysis of the AP2/ERF TFs family in C. acuminata was performed, including phylogeny, gene structure, conserved motifs, and gene expression profiles in different tissues and organs (immature bark, cotyledons, young flower, immature fruit, mature fruit, mature leaf, roots, upper stem, and lower stem) of C. acuminata. A total of 198 AP2/ERF genes were identified and divided into five relatively conserved subfamilies, including AP2 (26 genes), DREB (61 genes), ERF (92 genes), RAV (18 genes), and Soloist (one gene). The combination of gene expression patterns in different C. acuminata tissues and organs, the phylogenetic tree, the co-expression analysis with biosynthetic genes, and the analysis of promoter sequences of key enzymes genes involved in CPT biosynthesis pathways revealed that eight AP2/ERF TFs in C. acuminata might be involved in CPT synthesis regulation, which exhibit relatively high expression levels in the upper stem or immature bark. Among these, four genes (CacAP2/ERF123, CacAP2/ERF125, CacAP2/ERF126, and CacAP2/ERF127) belong to the ERF-B2 subgroup; two genes (CacAP2/ERF149 and CacAP2/ERF152) belong to the ERF-B3 subgroup; and two more genes (CacAP2/ERF095 and CacAP2/ERF096) belong to the DREB-A6 subgroup. These results provide a foundation for future functional characterization of the AP2/ERF genes to enhance the biosynthesis of CPT compounds of C. acuminata.

LC-MS/MS analysis of pazufloxacin in human plasma and otorrhea: application to a pharmacokinetic study of ear drops / 药学学报

Pazufloxacin eardrops are a topical quinolone agent for the treatment of outer ear infection. The present study evaluated the pharmacokinetics and topical distribution of pazufloxacin eardrops by a sensitive LC-MS/MS method for determining pazufloxacin in plasma and otorrhea. Plasma and otorrhea samples were extracted by acetonitrile-induced protein precipitation and were subjected to liquid chromatography-tandem mass spectrometric analysis with an electrospray ionization interface. The samples were separated on an HSS T3 column (50 mm×2.1 mm, 1.8 μm). To avoid the matrix effect, gradient elution was performed with the mobile phase consisting of methanol and 1 mmol·L-1 ammonium acetate aqueous solution (0.1% formic acid). The ion transitions for pazufloxacin and pazufloxacin-d4 were m/z 319.1→281.2 and m/z 323.1→285.2, respectively, under the multiple reaction monitoring (MRM) mode. The method was linear in the range of 0.010 0 - 8.00 ng·mL-1 for pazufloxacin in plasma and 0.500 - 1 000 ng·mg-1 in otorrhea. The intra- and inter-day accuracy and precision for pazufloxacin in plasma and in otorrhea met acceptable criteria. The clinical trial was approved by the Society of Ethics and conducted in Nanjing First Hospital and Jiangsu Province Hospital. The validated methods were used in a systemic and topical pharmacokinetic study of 0.1% pazufloxacin eardrops in 3 patients with chronic suppurative otitis media.

Effect of moxibustion at Feishu (BL 13) on airway inflammation in asthma model rats / 针灸推拿医学（英文版）

Objective: To observe the effect of moxibustion at Feishu (BL 13) on related inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid of asthma model rats, and to explore the mechanism of moxibustion in treating asthma. Methods: A total of 48 Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a moxibustion group and a medication group, with 12 rats in each group. Except for the normal group, the rats in the other three groups were subjected to ovalbumin sensitization to stimulate the asthma. At the same time, rats in the moxibustion group received moxibustion at bilateral Feishu (BL 13), and rats in the medication group received dexamethasone by intragastric administration. Rats in the normal and the model groups only received the same fixation and normal saline by intragastric administration. After the interventions, the inspiratory resistance, the expiratory resistance, and the pulmonary compliance were measured for rats in each group; the numbers of the inflammatory cells in the bronchoalveolar lavage fluid were counted; the levels of the involved inflammatory factors in bronchoalveolar lavage fluid were detected; the pathological morphologies of the lung tissues were observed under light microscope. Results: After modeling, compared with the normal group, the rats in the model group showed obvious asthma attack-like response, significantly increased inspiratory resistance and expiratory resistance (both P<0.01), and significantly reduced pulmonary compliance (P<0.01); thickened tracheal wall and the narrowed tracheal lumen observed under the light microscope; infiltration of inflammatory cells and increased eosinophils in and around the tracheal wall; significantly increased total number of inflammatory cells and proportion of eosinophils in the bronchoalveolar lavage fluid (all P<0.01); significantly reduced levels of interleukin (IL)-10, IL-12 and interferon (IFN)-γ (all P<0.01), and significantly increased levels of IL-4, IL-5 and tumor necrosis factor (TNF)-α (all P<0.01) in the bronchoalveolar lavage fluid. After intervention, compared with the model group, rats in the moxibustion and the medication groups showed significantly reduced asthma-like reaction, pathological morphological damage of lung tissue, inspiratory resistance and expiratory resistance (all P<0.01); significantly increased pulmonary compliance (P<0.01); significantly reduced total number of inflammatory cells, proportion of eosinophils, levels of IL-4, IL-5 and TNF-α in the bronchoalveolar lavage fluid (P<0.05 or P<0.01), while significantly increased IL-12 and IFN-γ levels (all P<0.01) in the bronchoalveolar lavage fluid; rats in the medication group also showed a significantly reduced IL-10 level in the bronchoalveolar lavage fluid (P<0.01); there was no statistically significant difference between the moxibustion and the medication groups (all P>0.05). Conclusion: Both moxibustion at Feishu (BL 13) and intragastric administration of dexamethasone can improve the asthma attack-like symptoms of ovalbumin-sensitized rats; regulating the inflammatory cell numbers and the inflammatory factor contents in the lung may be one mechanism of moxibustion in treating asthma.

Simultaneous Determination of Pyrrolidine Alkaloids and Their Nitrogen Oxides in Farfarae Flos by UPLC-MS/MS / 中国实验方剂学杂志

<b>Objective::To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the simultaneous determination of 15 pyrrolidine alkaloids (PAs) and their nitrogen oxides, and determine the content of the 15 PAs in the 15 batches of Farfarae Flos samples obtained from different sources, in order to understand the distribution status of these 15 PAs in Farfarae Flos from different sources, and provide relevant references for the safe and rational use of this medicinal materials. <b>Method::The method was achieved by Agilent Eclipse Plus C₁₈ column (3.0 mm×150 mm, 1.8 μm) using a mobile phase made up of 0.05%formic acid and 2.5 mmol·L^-1 ammonium formate in water (A)-0.05%formic acid and 2.5 mmol·L^-1 ammonium formate in methanol(B). The flow rate and the injection volume were 0.4 mL·min^-1 and 2 μL, respectively. The column temperature was 40 ℃. The instrument was Agilent 1290-6470 QQQ ultra high performance liquid chromatography-triple quaternary bar mass spectrometer. The components were detected in multiple reaction monitoring mode by mass spectrometry with ionizationmode of ESI⁺. The content of the components measured in the samples was calculated by using the external standard method, and the difference between samples was analyzed based on RSD of different components. <b>Result::The established method had a high sensitivity and good separation degree. The results of methodological investigation met the requirements. The results showed that all of the 15 batches of Farfarae Flos contained PAs and their nitrogen oxides. These PAs had almost the same types of structure. There were significant differences in the content and distribution of PAs in Farfarae Flos obtained from different sources. <b>Conclusion::In general, Farfarae Flos contains pyrrolidine alkaloids and their nitrogen oxides. Senkirkine with a significant hepatotoxicity is the main compound. The content determination of PAs will provide scientific fundaments for the safe and effective use of Farfarae Flos.

Prohibitin (PHB) interacts with AKT in mitochondria to coordinately modulate sperm motility / 亚洲男科学杂志(英文版)

Prohibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.

Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice / 北京大学学报(医学版)

OBJECTIVE@#Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world.@*METHODS@#We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated.@*RESULTS@#Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3.@*CONCLUSION@#Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

Effect of Traditional Chinese Medicine in Regulating Apoptosis and Autophagy Through mTOR Pathway / 中国实验方剂学杂志

Mammalian target of rapamycin (mTOR) is an evolutionary conservative serine/threonine protein kinase. Its biological function is mainly to participate in cell proliferation, growth and differentiation, so as to regulate the body's metabolic process. Many domestic and foreign studies have shown that mTOR is the junction of apoptosis and autophagy signal transduction pathways. Various stimuli, such as nutrition, drugs and oxidative stress, may play a key regulatory role in cell apoptosis and autophagy through mTOR-mediated signaling pathways. At present, many studies have shown that the change in mTOR signaling pathways is closely related to the pathogenesis of many human diseases, such as cancer, metabolic disorders(obesity and type 2 diabetes), cardiovascular and neurodegenerative disease, age-related diseases and disorders of follicular. In recent years, more and more doctors have studied the regulatory effect of traditional Chinese medicine on apoptosis and autophagy, with the pathways as the starting point and cell apoptosis and autophagy as the research carriers. These studies include experimental studies on the regulation of apoptosis and autophagy by monomers of traditional Chinese medicine (TCM), Chinese patent medicine, compound prescription of TCM, acupuncture and other drugs and physiotherapy. Starting from the mTOR signaling pathways, this paper discusses the relationship between mTOR, apoptosis and autophagy, and reviews the recent progress of TCM in regulating apoptosis and autophagy through mTOR pathways, so as to provide ideas and references for further studies in this field. In the future, TCM doctors can still explore the time-effect relationship between apoptosis and autophagy based on mTOR signaling pathways under the guidance of the basic theory of Chinese medicine, in order to provide theoretical support and targets for the action mechanism of TCM on bodies.

Commonality and pattern analysis of acupoint selection in moxibustion treatment of asthma / 针灸推拿医学（英文版）

Objective:To analyze and summarize the commonalities and patterns in acupoint selection for moxibustion treatment of asthma. Methods: Data retrieval was conducted using ‘moxibustion’ and ‘asthma’ as the keywords through China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang) and Chongqing VIP Database (CQVIP). Excel 2010 was used to establish the major acupoint database for moxibustion prescriptions in treatment of asthma; data mining methods including association patterns and clustering were adopted to analyze the characteristics and patterns in acupoint selection for moxibustion treatment of asthma. Results: A total of 161 moxibustion prescriptions were recruited. The most commonly used acupoint was Feishu (BL 13), the most commonly used meridian was the Bladder Meridian of Foot Taiyang, and the most commonly treated region was the back. The association rule analysis showed that Feishu (BL 13)-Dazhui (GV 14)-Fengmen (BL 12) had the most significant correlation, and the clustering analysis discovered 5 effective acupoint clusters. Conclusion: In moxibustion treatment of asthma, topical acupoints Feishu (BL 13), Dazhui (GV 14) and Fengmen (BL 12) can be selected, along with the acupoints from the Bladder Meridian of Foot Taiyang and the back.