Comparison of growth and quality of wild and cultivated Artemisia stolonifera / 中国中药杂志

This paper aims to compare the difference of growth and quality between wild and cultivated Artemisia stolonifera, thereby providing references for further development and utilization of A. stolonifera. The wild and cultivated A. stolonifera from different altitudes were collected, and the agronomic characters, moxa yield, volatile components, flavonoids, and phenolic acids were determined. The results showed that the cultivated species were taller and stronger, with more leaves and branches, than the wild species. The moxa yield and combustion quality of wild products were higher than those of cultivated products. The content of main volatile components in cultivated products was higher than that in wild products. The content of flavonoids and phenolic acids in wild products was higher than that in cultivated products. At high altitude, the ignition performance, combustion persistence, comprehensive combustion performance, and heat release during combustion of the wild and cultivated A. stolonifera. were optimal. At middle altitude, the content of main characteristic volatile components and flavone phenolic acids in the leaves of the cultivated and wild A. stolonifera were the highest. At low altitude, the combustion quality and the content of the above components of the cultivated A. stolonifera decrease significantly. Considering the combustion quality and the content of the internal components of the leaf lint, the middle and high altitude areas are suitable for the artificial cultivation of A. stolonifera.

Anti-inflammatory material basis and mechanism of Artemisia stolonifera based on UPLC-Q-TOF-MS combined with network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.

Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos / 中华预防医学杂志

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.

Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease / 中华心血管病杂志

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

Expert Consensus on Acute Respiratory Failure in Critically Ill Cancer Patients (2023) / 中国医学科学杂志(英文版)

Objective This consensus aims to provide evidence-based recommendations on common questions in the diagnosis and treatment of acute respiratory failure (ARF) for critically ill cancer patients.Methods We developed six clinical questions using the PICO (Population, Intervention, Comparison, and Outcome) principle in diagnosis and treatment for critical ill cancer patients with ARF. Based on literature searching and meta-analyses, recommendations were devised. The GRADE (Grading of Recommendation Assessment, Development and Evaluation) method was applied to each question to reach consensus in the expert panel. Results The panel makes strong recommendations in favor of (1) metagenomic next-generation sequencing (mNGS) tests may aid clinicians in rapid diagnosis in critically ill cancer patients suspected of pulmonary infections; (2) extracorporeal membrane oxygenation (ECMO) therapy should not be used as a routine rescue therapy for acute respiratory distress syndrome in critically ill cancer patients but may benefit highly selected patients after multi-disciplinary consultations; (3) cancer patients who have received immune checkpoint inhibitor therapy have an increased incidence of pneumonitis compared with standard chemotherapy; (4) critically ill cancer patients who are on invasive mechanical ventilation and estimated to be extubated after 14 days may benefit from early tracheotomy; and (5) high-flow nasal oxygen and noninvasive ventilation therapy can be used as a first-line oxygen strategy for critically ill cancer patients with ARFs. A weak recommendation is: (6) for critically ill cancer patients with ARF caused by tumor compression, urgent chemotherapy may be considered as a rescue therapy only in patients determined to be potentially sensitive to the anticancer therapy after multidisciplinary consultations. Conclusions The recommendations based on the available evidence can guide diagnosis and treatment in critically ill cancer patients with acute respiratory failure and improve outcomes.

Prediction analysis of quality markers and resource evaluation of Artemisiae Argyi Folium based on chemical composition and network pharmacology / 中国中药杂志

This study is based on ultra-high-performance liquid chromatography(UPLC), gas chromatography-mass spectrometry(GC-MS), and network pharmacology methods to analyze and predict potential quality markers(Q-markers) of Artemisiae Argyi Folium. First, UPLC and GC-MS techniques were used to analyze the content of 12 non-volatile components and 8 volatile components in the leaves of 33 Artemisia argyi germplasm resources as candidate Q-markers. Subsequently, network pharmacology was employed to construct a "component-target-pathway-efficacy" network to screen out core Q-markers, and the biological activity of the markers was validated using molecular docking. Finally, cluster analysis and principal component analysis were performed on the content of Q-markers in the 33 A. argyi germplasm resources. The results showed that 18 candidate components, 60 targets, and 185 relationships were identified, which were associated with 72 pathways related to the treatment of 11 diseases and exhibited 5 other effects. Based on the combination of freedom and component specificity, six components, including eupatilin, cineole, β-caryophyllene, dinatin, jaceosidin, and caryophyllene oxide were selected as potential Q-markers for Artemisiae Argyi Folium. According to the content of these six markers, cluster analysis divided the 33 A. argyi germplasm resources into three groups, and principal component analysis identified S14 as having the highest overall quality. This study provides a reference for exploring Q-markers of Artemisiae Argyi Folium, establishing a quality evaluation system, further studying its pharmacological mechanisms, and breeding new varieties.

Effect of apigenin in combination with oxymatrine on non-small cell lung cancer and mechanism / 中国中药杂志

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 μmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.

Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study / 中华外科杂志

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 μg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

Effect of electroacupuncture at "Neiguan" (PC 6) and "Zusanli" (ST 36) on gastrointestinal hormone in the antral tissue of rats with functional dyspepsia / 中国针灸

OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD.@*METHODS@#A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats.@*RESULTS@#In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group.@*CONCLUSIONS@#Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.

Locking plate fixation with fibular strut allograft versus locking plate fixation alone for the treatment of proximal humeral fractures in adults:a Meta-analysis / 中国骨伤

OBJECTIVE@#To compare the clinical efficacy of locking plate fixation with a fibular strut allograft (FA group) and locking plate fixation alone (LP group) in the treatment of proximal humeral fractures in adults by Meta-analysis.@*METHODS@#Databases including PubMed, The Cochrane Library, Embase, Chinese BioMedical Literature Database(CBM), China National Knowledge Infrastructure(CNKI), WanFang Data, and China Science and Technology Journal Database (cpvip Database) were searched by computer from establishing to March 2020 to collect studies about locking plate fixation with fibular strut allograft versus locking plate fixation alone for proximal humeral fractures in adults. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. The postoperative humeral head height changes, neck-shaft angle changes, Constant-Murley score, American Shoulder and Elbow Surgeons(ASES)score, visual analogue scale(VAS), varus malunion rate, and screw penetration rate were compared by RevMan 5.3 software for Meta-analysis.@*RESULTS@#Ten cohort studies were enrolled in a total of 749 patients, 300 patients in the FA group and 449 patients in the LP group. The results of Meta-analysis showed that locking plate with fibular strut allograft was superior to locking plate fixation alone in the changes in humeral head height [MD=-2.69, 95%CI(-3.24, -2.13), P<0.000 01], the changes in neck-shaft angle [MD=-5.65, 95%CI(-7.18, -4.12), P<0.000 01], Constant-Murley score [MD=9.00, 95%CI(4.26, 13.73), P=0.000 2], the ASES score [MD=5.56, 95%CI(4.29, 6.84), P=0.000 01], VAS score [MD=-0.23, 95%CI(-0.37, -0.09), P=0.001], the varus malunion rate [RR=0.22, 95%CI(0.09, 0.53), P=0.000 7] and the screw penetration rate [RR=0.26, 95%CI(0.13, 0.55), P=0.000 3], respectively.While there was no significant difference in the rate of osteonecrosis of the humeral head [RR=1.18, 95%CI(0.57, 2.45), P=0.65].@*CONCLUSION@#For proximal humeral fractures in adults, current evidence shows that locking plate fixation with fibular strut allograft is superior to single locking plate fixation in improving postoperative radiological outcomes and shoulder function, relieving postoperative pain, reducing varus malunion rate and screw penetration rate. However, the efficacy in decreasing the osteonecrosis rate is not clear. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusion.

A new classification of maxillary defect and simultaneous accurate reconstruction / 中华耳鼻咽喉头颈外科杂志

Objective: To select the preferred flaps for the reconstruction of different maxillary defects and to propose a new classification of maxillary defects. Methods: A total of 219 patients (136 males and 83 females) underwent the simultaneous reconstruction of maxillary defects in the Beijing Tongren Hospital, Capital Medical University, between January 2005 and December 2018 were reviewed. Age ranged from 16 to 78 years. Based on the proposed new classification of the maxillary defects, 22 patients with class Ⅰ defects (inferior maxillectomy), 44 patients with class Ⅱ defects (supperior maxillectomy), 132 patients with class Ⅲ defects (total maxillectomy) and 21 patients with class Ⅳ defects (extensive maxillectomy) were enrolled. Survival rate, functional and aesthetic outcomes of flaps were evaluated. Survival analysis was performed in 169 patients with malignant tumor, Kaplan-Meier method was used to calculate the survival rate, and Log-rank method was used to compare the difference of survival rate in each group. Results: A total of 234 repairs for maxillary defects were performed in 219 patients. Fibula flaps were used in 4/13 of class Ⅰ defects; temporal muscle flaps (11/24, 45.8%) and anterolateral thigh flaps (6/24, 25.0%) used in class Ⅱ defects; temporal muscle flaps (71/128, 55.5%), anterolateral thigh flaps (6/24, 25.0%) and fibula flaps (12/128, 9.4%) used in class Ⅲ defects; and anterolateral thigh flaps (8/20, 40.0%) and rectus abdominis flaps (8/20, 40.0%) used in class Ⅳ defects. The success rate of local pedicled flaps was 95.6% (109/114) and that of free flaps was 95.8% (115/120). Thrombosis(10/234,4.3%) was a main reason for repair failure. Among the followed-up 88 patients, swallowing and speech functions recovered, 82 (93.2%) of them were satisfied with appearance, and 75 (85.2%) were satisfied with visual field. The 3-year and 5-year overall survival rates were 66.5% and 63.6%, and the 3-year and 5-year disease-free survival rates were 57.1% and 46.2%, respectively, in the 169 patients with malignant tumors. Conclusion: A new classification of maxillary defects is proposed, on which suitable flaps are selected to offer patients good functional and aesthetic outcomes and high quality of life.

Sacubitril/valsartan attenuates left ventricular remodeling and improve cardiac function by upregulating apelin/APJ pathway in rats with heart failure / 中华心血管病杂志

Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg-1·d-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 μg·kg-1·d-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.

Effect of Main Component of Realgar Arsenic Disulfide （As2S2） on DNA Methylation of SKM-1 Cells with Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the effects of the main component of Realgar arsenic disulfide （As2S2） on DNA methylation of SKM-1 cells with myelodysplastic syndrome. MethodCell Counting Kit-8 （CCK-8） was used to detect the inhibitory effect of As2S2（0， 1， 2， 4， 8， 16 μmol·L-1）on SKM-1 cells. Propidium iodide （PI） staining was applied to detect the effect of As2S2（0， 1， 2， 4 μmol·L-1）on the SKM-1 cell cycle. The effect of As2S2 （0， 4 μmol·L-1） on the methylation of SKM-1 cells on a genome-wide scale was observed by using Human Methylation 850K BeadChip， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） and gene ontology （GO） analyses. According to the microarray data， the antioncogene TUSC3 was selected， and real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were adopted to investigate the effect of As2S2 （0， 1， 2， 4 μmol·L-1） on the mRNA and protein expression of TUSC3， respectively. ResultCompared with the conditions in the blank group， As2S2 inhibited SKM-1 cells， increased the proportion of cells in the G0/G1 phase， and decreased the proportion of cells in the S phase（P<0.05）. The 850K microarray showed that 4 μmol·L-1 As2S2 could significantly induce DNA methylation in SKM-1 cells， with 12 710 differentially methylated genes involved （50% hypermethylated and 50% hypomethylated genes）. KEGG and GO analyses showed that differentially methylated genes were involved in many important biological functions and signaling pathways， including purine metabolism， natural killer cell-mediated cytotoxicity， endocytosis， chemokine signaling pathway， and nuclear ubiquitin ligase complex. In terms of downstream gene expression， Real-time PCR and Western blot showed that As2S2 increased the expression of TUSC3， as compared with the conditions in the blank group （P<0.05）. ConclusionAs2S2， the main component of Realgar， has a significant regulatory effect on the methylation of SKM-1 cells， which is presumedly achieved by increasing the expression of TUSC3.

Spatial heterogeneity and physical structure basis of antibacterial activity of Ma-Xing-Shi-Gan Decoction / 药学学报

Ma-Xing-Shi-Gan Decoction is a classic prescription. However, the interaction among multiple components of the decoction and the change of phase state are not clear. Moreover, the relationship between the physical phase state aggregated by multiple components and the efficacy still needs to be studied. In this study, we monitored the particle size changes of Ma-Xing-Shi-Gan Decoction in real time. Then we isolated different phase states by centrifugation, analyzed their composition distribution and tested their antibacterial activity. We added chemical interference agents to investigate the interaction of multi-component physical phase states accompanied by the observation of particle size change and morphology. We also studied the correlation between antibacterial activity and physical structure of phase states. The results showed during boiling process the degree of hybridization of particles was decreased and the particle size distribution was narrowed and stabilized at 170 nm. The distribution of organic and inorganic components was heterogeneous among different phase states. S-13500, supernatant isolated by 13 500 ×g centrifugation, constituted by ephedrine, amygdalin, glycyrrhizic acid and inorganic components Ca, K, Mg, etc., had the strongest antibacterial activity. The molecular interaction force in the active physical phase state was mainly hydrophobic and hydrogen bond. The destruction of the interaction force will lead to the change of phase structure and the decrease of antibacterial activity in vitro and in vivo. This study confirms that, in the boiling process of the Ma-Xing-Shi-Gan Decoction, the chemical components interweave and interact to form new physical phase states, leading to heterogeneous distribution of components. The antimicrobial activity of the active phase depends on both chemical composition and physical structure, which provides a direct evidence for the physical basis of the efficacy of traditional Chinese medicine.

Preparation and properties of extracellular vesicle-like nanoparticles from medicinal and edible plants / 药学学报

Extracellular vesicle-like nanoparticles (EVNs) isolated from edible plants have been shown to have multiple activities, while EVNs from medicinal plants have rarely been reported. In this paper, medicinal parts of medicinal and edible homologous fresh Curcumae Longae Rhizoma (CLR), Lilii Bulbus (LB), Polygonati Rhizoma (PR), and Gastrodiae Rhizoma (GR) are used to squeeze juice to collect EVNs. The physical and chemical properties, antioxidant capacity, and cellular uptake behavior of EVNs are determined. The results show that the particle size of EVNs from different sources ranges from 150 nm to 200 nm, and the polydispersity index (PDI) values of four EVNs are less than 0.2. Different EVNs all contain lipids, proteins, and carbohydrates, but their contents are different. The stability of EVNs is different at 4 ℃ and -80 ℃, among which the CLR-derived EVNs are most stable. Antioxidant experiments confirm that the four EVNs have different antioxidant activities while structural damage of EVNs leads to the reduced antioxidant capacity. Cellular uptake studies prove that four EVNs differ in the uptake capacity by RAW264.7 cells, which is associated with the structural interference of EVNs. The available evidence implies that the specific structure of EVNs may be necessary to their pharmacological activity and transport property.

Research progress of plant-derived vesicles and their biomedical applications / 药学学报

Plant-derived extracellular vesicles (EVs) are membranous vesicles secreted by plants, which include lipid bilayer as the basic framework and encapsulate various proteins, nucleic acid and other active substances. They play an important role in plant growth and development, tissue repair and self-defense. In recent years, extracellular vesicle-like nanoparticles (EVNs) are prepared from plant samples referring to the separation method of EVs and show unique functions. In this review, the above structures are collectively called plant-derived vesicles (PDVs). The biogenesis, separation and characterization methods, in vivo and in vitro properties of PDVs have been reviewed. The biomedical applications of PDVs as natural therapeutic agents and functional drug carriers are described, and finally some opinions on the existing problems and future prospect in this field are put forward.

Active fractions of Camellia nitidissima inhibit non-small cell lung cancer via suppressing epidermal growth factor receptor / 中国中药杂志

The present study explored the effects and its underlying mechanisms of four active fractions of Camellia nitidissima(leaf polyphenols, leaf saponins, flower polyphenols, and flower saponins in C. nitidissima) in inhibiting the proliferation and migration of non-small cell lung cancer(NSCLC) by suppressing the epidermal growth factor receptor(EGFR). MTT assay was used to detect the effect of four active fractions on the proliferation of NCI-H1975 and HCC827 cells. Wound healing assay and Transwell assay were adopted to evaluate the effect of four active fractions on the migration of NSCLC. The effect of four active fractions on the enzyme activity of EGFR was detected. Molecular docking was carried out to explore the direct action capacity and action sites between representative components of the four active fractions and EGPR. Western blot assay was employed to investigate the effect of four active fractions on the protein expression in EGFR downstream signaling pathways. The results of the MTT assay indicated that the cell viability of NCI-H1975 and HCC827 cells was significantly inhibited by four active fractions at 50, 100, 150, and 200 μg·mL~(-1) in a dose-dependent manner. Wound healing assay and Transwell assay revealed that the migration of NCI-H1975 and HCC827 cells was significantly suppressed by four active fractions. In addition, the results of the protein activity assay showed that the enzyme activity of EGFR was significantly inhibited by four active fractions. The molecular docking results confirmed that various components in four active fractions possessed strong binding activity to EGFR enzymes. Western blot assay revealed that four active fractions down-regulated the protein expression of EGFR and its downstream signaling pathways. It is concluded that the four active fractions of C. nitidissima can inhibit NSCLC. The mechanism may be related to EGFR and its downstream signaling pathways. This study provides a new scientific basis for the clinical treatment of NSCLC with active fractions of C. nitidissima, which is of reference significance for further research on the anti-tumor mechanism of C. nitidissima.

Retrospective study of thyroid invasion and central lymph node metastasis in 124 patients with hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of thyroid invasion and central lymph node metastasis of hypopharyngeal carcinoma, and the impact on survival rate and quality of life. Methods: A retrospective analysis of 124 cases (122 males and 2 females with age range from 36 to 78 years old) with laryngopharyngeal squamous cell carcinoma who were initially treated in the Department of Head and Neck Surgery, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2014 to December 2017 was performed. The clinical data included tumor location, pathological T stage, pathological N stage, invasion of thyroid gland, central lymph node metastasis, surgical procedures and so on. Patients were grouped according to if presence of thyroid invasion and central lymph node metastasis. With follow-up, the survival was analyzed by Kaplan-Meier method, and tumor recurrence and metastasis were evaluated. Results: Of the patients, 12 patients had thyroid involvement and 5 patients had central lymph node metastasis. The incidence of thyroid involvement was 8.16% (8/98) in pyriform sinus, 1/18 in posterior pharyngeal wall and 3/8 in posterior cricoid wall, with statistically significant difference (χ2=15.076,P=0.008). The incidence of central lymph node metastasis was 1.02% (1/98) in pyriform sinus, 3/18 in posterior pharyngeal wall and 1/8 in posterior cricoid wall, also with statistically significant difference (χ2=11.205, P=0.008). There was no statistical correlation between thyroid invasion or central lymph node metastasis and gender, smoking or alcohol exposure history and tumor pathological differentiation (all P>0.05). The 3-year overall survival rate was 80.65% and the 3-year recurrence free rate was 85.48%. Totally 24 patients died in 3 years, including 4 cases in thyroid invasion group and 1 case in central lymph node metastasis group. Local recurrence occurred in 18 patients, including 4 cases in thyroid invasion group and 1 case in central lymph node metastasis group. There was no significant difference in survival between patients with and without thyroid invasion and central lymph node metastasis (all P>0.05). There were significantly difference in 3-year overall survival and relapse-free survival among the groups with different T stages, N stages, pathological stages and tumor pathological differentiation levels (all P<0.05). There were significantly differences in the levels of serum calcium and FT3 between the groups with or without thyroid invasion and central lymph node metastasis (all P<0.05). Conclusion: The incidences of thyroid invasion and central lymph node metastasis of hypopharyngeal carcinoma are rare, and the risk of occurrence is related to the primary site of tumor. Comprehensive evaluation, correct decision-making and accurate treatment could be helpful to cure radically the tumor, to prevent recurrence and to improve the quality of life of patients.

Structural Chinese medicine: new research field on pharmacodynamic substance basis of traditional Chinese medicine / 中国中药杂志

The research on the pharmacodynamic substance basis of traditional Chinese medicine(TCM) is a key scientific issue for the inheritance and development of TCM. At present, a large number of remarkable achievements have been made in the field of chemical components in Chinese medicine, however, another important aspect, namely the physical structure and mode of action of the multi-component assembly of TCM, has not been clearly understood and deeply studied. From the bottleneck of restricting material ba-sic research, we objectively analyzed the common cause of the existing problems. Based on the new discoveries and advances of active substances from TCM emerging in recent years, we extracted and summarized the concept of structural Chinese medicine, elaborated the basic ideas, main features and research modes, hoping to provide theoretical and practical references for the study on the pharmacodynamic substance basis and other research fields of TCM.

Effect of different drying methods on drying characteristics, appearance and active components of Belamcandae Rhizoma / 中国中药杂志

In order to explore the effect of different drying methods(drying-in-the-shade, sun-drying, and hot air drying) on appearance characteristics, internal structure and composition of Belamcandae Rhizoma, so as to provide a theoretical basis for screening out suitable drying methods for primary processing. In this study, the Belamcandae Rhizoma's dynamic changes of the moisture content ratio and drying rate with different drying time under different drying methods, as well as the effects of different drying methods on the appearance, drying rate, density, ash, extractives and the contents of six flavonoids(mangiferin, tectoridin, iridin, tectorigenin, irigenin, irisflorentin) were compared. The results showed that fresh Belamcandae Rhizoma consumed the longest time to reach the water balance point by traditional dry drying in the shade, whiche was about 311 h; that by sun drying was 19.3%, which was shorter than drying in the shade; both drying curves were smoother. The section color of the sun drying samples was the closest to that of fresh samples, but the interior is full of holes, with a low density and loose structure. Hot air drying(40, 60, 80 ℃) could save about 27% to 88% of the drying time, which was greatly shorter, with less pores, a larger density and compact structure. Compared with the traditional drying method, the drying rate of hot air drying was reduced by 13.7%. Ash was affected by temperature, the drying conditions under 40 ℃ and below were not significantly different from those of conventional drying. The ash content decreased by 7.73% to 18.5% compared with conventional drying at 60,80 ℃. After conventional drying and 40 ℃ hot air drying, the contents of tectoridin and iridin(glycosides) in the samples were significantly higher than those in 60,80 ℃ hot air drying, while the contents of tectorigenin, irigenin and irisflorentin(aglycones) dried at 60 ℃ were the best. Therefore, considering comprehensive appearance characteristics and content of medicinal ingredients, traditional Chinese medicinal materials after 60 ℃ hot air drying show a solid texture, tight internal structure, good appearance, appropriate reduction of toxic parasides and higher aglycone content.