Study on quality control method of the roots and rhizoma of Toricellia angulata / 中国药房

OBJECTIVE To establish the quality control method for the roots and rhizoma of Toricellia angulata. METHODS The properties of the roots and rhizoma of T. angulata were observed and microscopic identification was conducted. The moisture， total ash， acid-insoluble ash and ethanol-soluble extract were examined according to the method stated in the 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata were established， common peaks were identified and the similarity was evaluated by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）. The contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol were determined by HPLC. RESULTS The properties and microscopic identification of the roots and rhizoma of T. angulata were obvious. The average contents of moisture， total ash， acid-insoluble ash and ethanol-soluble extract were 7.54%， 2.18%， 0.15% and 7.81%， respectively. There were 16 common peaks marked in the HPLC fingerprints of 11 batches of the roots and rhizoma of T. angulata， with similarities of 0.856-0.960； five of them were identified， such as coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D-glucopyranoside and syringaresinol. The contents of the above five components were 0.047 2-0.401 6， 0.836 8-8.697 9， 1.245 3-10.950 0， 0.139 0-0.437 8 and 0.016 4-0.635 3 mg/g， respectively. CONCLUSIONS The established method is stable and accurate， which can be used for the quality control of the roots and rhizoma of T. angulata. It is preliminarily proposed that the moisture in the roots and rhizoma of T. angulata is not more than 11.0%， the total ash is not more than 4.0%， the ethanol-soluble extract is not less than 5.0%， the contents of coniferin， syringin， chlorogenic acid， （+）-syringaresinol-O-β-D- glucopyranoside and syringaresinol are not less than 0.04，0.83， 1.24， 0.13， 0.01 mg/g， respectively.

Experimental study of curcumol inhibiting vascular endothelial growth factor-induced neovascularization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the role and mechanism of curcumol in neovascularization induced by vascular endothelial growth factor(VEGF).METHODS: Human umbilical vein endothelial cells were cultured in vitro and treated with 50ng/mL VEGF and curcumol at different concentrations. Cell proliferation was detected by CCK-8 and EdU assay, the migration ability of cells was analyzed by Transwell assay, the angiogenesis ability of endothelial cells was analyzed by tube formation assay, and the change of Akt/mTORC1 signal pathway was detected by Western blot.RESULTS: CCK-8 results showed that the OD450 value of cells in 400 and 800 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(all P<0.01). EdU results showed that the rate of cell proliferation in 400 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(P<0.001). Transwell assay and the formation assay results showed that the number of migratory cells in 400 μmol/L curcumol+VEGF group was decreased, and the number and length of tube branches were also reduced compared with VEGF group(all P<0.001). Western blot results showed that curcumol significantly inhibited the expression of p-Akt and p-S6, which were downstream targets of Akt/mTORC1 pathway in cells.CONCLUSION: Curcumol can inhibit VEGF-induced cell proliferation, migration and tube formation of vein endothelial cells, and has a strong inhibitory effect on angiogenesis, which can be further studied in the treatment of ocular fundus neovascularization.

Influence of system relaxation training on the posttraumatic stress disorder for the families of burned children / 中国实用护理杂志

Objective:To investigate the application of system relaxation training on the posttraumatic stress disorder for the families of burned children, so as to provide a basis for the application of valid nursing in children families.Methods:A total of 80 cases of burned children in Children′s Hospital of Nanjing Medical University and corresponding 80 households were recruited and divided into the observation group and the control group with 40 cases each group. The patients and households from January 2019 to May 2019 in the control group received routine care, while the patients and households from February 2020 to June 2020 in the observation group received system relaxation training based on the routine care for four days. The posttraumatic stress disorder and uncertainty in illness of children families before and after intervention were evaluated by Posttraumatic stress Checklist-Civilian version(PLC-C) and Mishel Uncertainty in Illness Scale-Family Member form(MUIS-FM) and compared between the two groups.Results:There was no significant difference in the scores of PLC-C and MUIS-FM before intervention in the households between the two groups( P>0.05). After intervention, the scores of re-experiencing symptoms, avoidance/numbing, increased arousal symptoms and total PTSD scores in the households were (8.40 ± 1.79), (14.35 ± 2.85), (8.25 ± 1.28), (31.10 ± 3.52) points in the observation group and (11.28 ± 2.37), (16.75 ± 2.09), (9.10 ± 1.93), (37.13 ± 4.40) points in the control group, the differences were statistically significant ( t values were -6.76 - -2.32, all P<0.05). After intervention, the scores of ambiguity, deficit information and total MUIS-FM scores of the households were (37.08 ± 6.58), (20.15 ± 4.38), (84.38 ± 6.90) points in the observation group and (41.13 ± 6.54), (22.05 ± 3.32), (90.13 ± 7.85) points in the control group, the differences were statistically significant ( t =-2.76, -2.19, -3.48, all P<0.05). Conclusions:System relaxation training can alleviate posttraumatic stress disorder and reduce uncertainty in illness of the families of burned children.

New progress in the diagnosis and treatment of thiamine responsive megaloblastic anemia syndrome / 中华实用儿科临床杂志

Thiamine responsive megaloblastic anemia syndrome is a rare autosomal recessive disease caused by mutations of the SLC19A2 gene that encodes the high-affinity thiamine transporter-1.Thiamine responsive megaloblastic anemia syndrome involves extensive organs and systems with various clinical manifestations.The typical triad is megaloblastic anemia, non-autoimmune diabetes, and sensorineural deafness.The diagnosis of thiamine responsive megaloblastic anemia syndrome depends on the detection of the pathogenic gene SLC19A2.Thiamine replacement therapy is the first-line treatment.Blood glucose of patients with thiamine responsive megaloblastic anemia syndrome should be comprehensively managed, and hearing aids and cochlear implants can be used to improve the hearing.

Curcumin alleviates the manganese-induced neurotoxicity by promoting autophagy in rat models of manganism / 北京大学学报(医学版)

OBJECTIVE@#To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl2), which mimics mangnism.@*METHODS@#Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H2O intragastrically (ig), MnCl2 group received 15 mg/kg MnCl2(Mn2+ 6.48 mg/kg) intraperitoneally plus dd H2O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl2+ CUR1 group received 15 mg/kg MnCl2 intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl2+ CUR2 group received 15 mg/kg MnCl2 intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum.@*RESULTS@#After exposure to MnCl2 for four weeks, MnCl2-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH+ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl2 group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl2 group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl2 group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl2+ CUR2 group were significantly improved compared with MnCl2 group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl2+ CUR2 group compared with MnCl2 group. Further, compared with MnCl2 group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl2+ CUR2 group (P < 0.05).@*CONCLUSION@#Curcumin alleviated the MnCl2-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.

A Breakthrough Point in Integrative Medical Research: Challenge of Treating Overlapping Symptoms in Functional Gastrointestinal Disorders / 中国结合医学杂志

Functional gastrointestinal disorders (FGIDs) are common disorders that are characterized by persistent and recurring gastrointestinal symptoms. Many patients with FGIDs have overlapping symptoms, which impaired the quality of life and ability to work of patients, and left a considerable impact on health-care systems and society. Chinese medicines (CMs) are commonly utilized by many patients with FGIDs. This article discusses the current status of diagnosis and treatment of FGIDs, the advantages and characteristics of CM treatment, and how integrated medicine can make a breakthrough in FGIDs diagnosis and treatment.

Improvement of the quality standard of Gerbera piloselloides / 中国药房

OBJECTIVE To improve th e quality standard for Gerbera piloselloides. METHODS The properties of G. piloselloides were observed and microscopic identification was conducted for powder. The moisture ，total ash ，acid-insoluble ash and ethanol-soluble extract were detected according to the method stated in 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. The contents of nodakenin，luteolin-7-O-β-D-lutinoside，luteoloside，apigenin-7-O-β-D-lutinoside，apigenin-7-O-β-D-glucopyranoside and marmesin were determined by high performance liquid chromatography method. RESULTS G. piloselloides were shrunken ，densely covered with thick white cotton wool ，with many fibrous roots ；the surface was taupe or gray-brown ；its texture was brittle and easy to break ；the cross section was yellow-white ，and there was an obvious small wooden heart in the center. Its powder was tan ， and non-glandular hairs ，stone cells ，calcium oxalate cubes ，ducts，fibers could be seen unde r microscope. The measured values of moisture，total ash ，acid-insoluble ash and alcohol-soluble extract ， for 15 batches of samples were 8.63％-11.34％，10.39％-14.93％， 3.29％-6.37％ and 9.03％-15.02％，respectively；average values were 10.01％，12.26％，4.61％，12.36％. The linear ranges of nodakenin，luteolin-7-O-β-D-rutinoside，luteoloside，apigenin- 7-O-β-D-lutinoside，apigenin-7-O-β-D-glucopyranoside and marmesin we re 3.87-154.88，1.64-65.41，1.60-64.00，1.92-76.96， 1.27-50.93，0.40-15.89 μg/mL，respectively（r≥0.999 1）. RSDs of precision ，stability（24 h）and repeatability tests were all less than 3％. The average recoveries were 101.88％，100.89％，102.64％，95.75％，96.71％ and 103.48％，respectively；RSDs were 0.55％，0.43％，0.34％，0.49％，0.47％ and 0.37％，respectively（n＝6）；the contents of above 6 components were 0.152 7-0.852 2， 0.084 5-0.669 7，0.136 7-0.961 0，0.126 0-1.193 2，0.128 8-1.102 2，0.046 9-0.678 0 mg/g. CONCLUSIONS The established method can be used for the quality control of G. piloselloides . It is preliminarily proposed that the moisture in G. piloselloides is not more than 12.0％；the total ash is not more than 15.0％，the acid-insoluble ash is not more than 6.0％，the alcohol-soluble extract is not less than 9.0％；the contents of luteoloside and apigenin- 7-O-β-D-glucopyranoside are not less than 0.016％.

Exploratory screening of potential pan-cancer biomarkers based on The Cancer Genome Atlas database / 北京大学学报(医学版)

OBJECTIVE@#To screen potential pan-cancer biomarkers based on The Cancer Genome Atlas (TCGA) database, and to provide help for the diagnosis and prognosis assessment of a variety of cancers.@*METHODS@#"GDC Data Transfer Tool" and "GDCRNATools" packages were used to obtain TCGA database. After data sorting, a total of 13 cancers were selected for further analysis. False disco-very rate (FDR) < 0.05 and fold change (FC) >1.5 were used as the differential expression criteria to screen genes and miRNAs that were up- or down-regulated in all the 13 cancers. In the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), the best cut-off value and the corresponding sensitivity and specificity were used to reflect diagnostic significance. The Kaplan-Meier method was used to calculate the survival probability and then the log-rank test was performed. Hazard ratio (HR) was calculated to reflect prognostic evaluation significance. DAVID tool were used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for differentially expressed genes. STRING and TargetScan tools were used to analyze the regulatory network of differentially expressed genes and miRNAs.@*RESULTS@#A total of 48 genes and 2 miRNAs were differentially expressed in all the 13 cancers. Among them, 25 genes were up-regulated, 23 genes and 2 miRNAs were down-regulated. Most differentially expressed genes and miRNAs had good ability to distinguish between the cases and controls, with AUC, sensitivity and specificity up to 0.8-0.9. Survival analysis results show that differentially expressed genes and miRNAs were significantly associated with patient survival in a variety of cancers. Most up-regulated genes were risk factors for patient survival (HR>1), while most down-regulated genes were protective factors for patient survival (0 < HR < 1). The enrichment analysis of GO and KEGG showed that the differentially expressed genes were mostly enriched in biological events related to cell proliferation. In the regulatory network analysis, a total of 13 differentially expressed genes and 2 differentially expressed miRNAs had regulatory and interaction relationships.@*CONCLUSION@#The 48 genes and 2 miRNAs that were differentially expressed in 13 cancers may serve as potential pan-cancer biomarkers, providing help for the diagnosis and prognosis evaluation of a variety of cancers, and providing clues for the development of broad-spectrum tumor therapeutic targets.

Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of Tojapride, a Chinese herbal formula extract, on strengthening the barrier function of esophageal epithelium in rats with reflux esophagitis (RE).@*METHODS@#Ten out of 85 SD rats were randomly selected as the sham group (n10), and 75 rats were developed a reflux esophagitis model (RE) by the esophageal and duodenal side-to-side anastomosis. Fifty successful modeling rats were divided into different medicated groups through a random number table including the model, low-, medium-, and high-dose of Tojapride as well as omeprazole groups (n10). Three doses of Tojapride [5.73, 11.46, 22.92 g/(kg•d)] and omeprazole [4.17 mg/(kg•d)] were administrated intragastrically twice daily for 3 weeks. And the rats in the sham and model groups were administered 10 mL/kg distilled water. Gastric fluid was collected and the supernatant was kept to measure for volume, pH value and acidity. Esophageal tissues were isolated to monitor the morphological changes through hematoxylin-eosin (HE) staining, and esophageal epithelial ultrastructure was observed by transmission electron microscopy. The expressions of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-KBp65), κB kinase beta (IKKß), occludin, and zonula occludens-1 (ZO-1) in the esophageal tissues were measured by immunohistochemistry and Western blot, respectively.@*RESULTS@#The gastric pH value in the model group was significantly lower than the sham group (P<0.05). Compared with the model group, gastric pH value in the omeprazole and medium-dose of Tojapride groups were significantly higher (P<0.05). A large area of ulceration was found on the esophageal mucosa from the model rats, while varying degrees of congestion and partially visible erosion was observed in the remaining groups. Remarkable increase in cell gap width and decrease in desmosome count was seen in RE rats and the effect was reversed by Tojapride treatment. Compared with the sham group, the IKKß levels were significantly higher in the model group (P<0.05). However, the IKKß levels were down-regulated after treatment by all doses of Tojapride (P<0.01 or P<0.05). The occluding and ZO-1 levels decreased in the model group compared with the sham group (Ps0.01 or Ps0.05), while both indices were significantly up-regulated in the Tojapride-treated groups (P<0.01 or P<0.05).@*CONCLUSIONS@#Tojapride could improve the pathological conditions of esophageal epithelium in RE rats. The underlying mechanisms may involve in down-regulating the IKKß expression and elevating ZO-1 and occludin expression, thereby alleviating the inflammation of the esophagus and strengthening the barrier function of the esophageal epithelium.

Effects of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes complicating hypertension: a meta-analysis / 中华心血管病杂志

Objective: To analyze the effects of different types of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on 24-hour ambulatory blood pressure in patients with type 2 diabetes mellitus and hypertension. Method: In this meta-analysis, we searched for randomized controlled trials on the effect of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension. Three databases, namely PubMed, Web of Science and Cochrane Library, were searched. The search was organized on the concept of 3 conceptual groups: the first group contained terms used to describe SGLT2i, the second group contained terms related to blood pressure, and the third group contained terms used to describe randomized controlled trials. The search time was from the establishment of the database to December 2020. The inclusion and exclusion criteria were formulated in accordance with the requirements of the Cochrane systematic review. According to whether the heterogeneity of the study was significant or not, a random effect model or a fixed effect model were used to conduct the analysis on the impact of different types of SGLT2i on 24-hour ambulatory blood pressure and day and night blood pressure in patients with type 2 diabetes and hypertension. Further subgroup analysis was performed to define potential factors, which might lead to clinical heterogeneity. Results: Seven clinical trials were finally included. The result of the meta-analysis showed that compared with placebo group, SGLT2i could reduce the 24-hour dynamic systolic blood pressure of patients with type 2 diabetes and hypertension by 4.36 mmHg (1 mmHg=0.133 kPa). Reduction was 4.59, 3.74, 5.06, and 3.64 mmHg by canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin respectively; SGLT2i could reduce the 24-hour dynamic diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.20 mmHg, and the reduction was 2.30, 1.22, 2.00, and 2.69 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin respectively. SGLT2i could reduce the daytime systolic blood pressure of patients with type 2 diabetes and hypertension by 5.25 mmHg, and reduction was 5.38, 4.87, 6.00, and 4.37 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. Simultaneously, SGLT2i could reduce the diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.62 mmHg, and the reduction was 2.56, 2.47, and 2.80 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. SGLT2i could reduce the nighttime systolic blood pressure of patients with type 2 diabetes and hypertension by 3.62 mmHg, and the reduction was 2.09, 2.06, 3.92, and 2.45 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. At the same time, SGLT2i could reduce the nighttime diastolic blood pressure of patients with type 2 diabetes and hypertension by 1.60 and 1.51 mmHg, the reduction was 1.53 and 2.58 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. Conclusion: SGLT2i can reduce 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension.

Effect of active component compound of Epimedii Folium,Astragali Radix,and Puerariae Lobatae Radix on expression of ADAM17 in HT22 cells by mediating hepcidin / 中国中药杂志

Alzheimer's disease(AD) patients in China have been surging, and the resultant medical burden and care demand have a huge impact on the development of individuals, families, and the society. The active component compound of Epimedii Folium, Astragali Radix, and Puerariae Lobatae Radix(YHG) can regulate the expression of iron metabolism-related proteins to inhibit brain iron overload and relieve hypofunction of central nervous system in AD patients. Hepcidin is an important target regulating iron metabolism. This study investigated the effect of YHG on the expression of a disintegrin and metalloprotease-17(ADAM17), a key enzyme in the hydrolysis of β amyloid precursor protein(APP) in HT22 cells, by mediating hepcidin. To be specific, HT22 cells were cultured in vitro, followed by liposome-mediated siRNA transfection to silence the expression of hepcidin. Real-time PCR and Western blot were performed to examine the silencing result and the effect of YHG on hepcidin in AD cell model. HT22 cells were randomized into 7 groups: control group, Aβ25-35 induction(Aβ) group, hepcidin-siRNA(siRNA) group, Aβ25-35 + hepcidin-siRNA(Aβ + siRNA) group, Aβ25-35+YHG(Aβ+YHG) group, hepcidin-siRNA+YHG(siRNA+YHG) group, Aβ25-35+hepcidin-siRNA+YHG(Aβ+siRNA+YHG) group. The expression of ADAM17 mRNA in cells was detected by real-time PCR, and the expression of ADAM17 protein by immunofluorescence and Western blot. Immunofluorescence showed that the ADAM17 protein expression was lower in the Aβ group, siRNA group, and Aβ+siRNA group than in the control group(P<0.05) and the expression was lower in the Aβ+siRNA group(P<0.05) and higher in the Aβ+YHG group(P<0.05) than in the Aβ group. Moreover, the ADAM17 protein expression was lower in the Aβ+siRNA group(P<0.05) and higher in the siRNA+YHG group(P< 0.05) than in the siRNA group. The expression was higher in the Aβ+siRNA+YHG group than in the Aβ+siRNA group(P<0.05). The results of Western blot and real-time PCR were consistent with those of immunofluorescence. The experiment showed that YHG induced hepcidin to up-regulate the expression of ADAM17 in AD cell model and promote the activation of non-starch metabolic pathways, which might be the internal mechanism of YHG in preventing and treating AD.

New dibenzoxocin derivatives from Caesalpinia decapetala / 中国中药杂志

The present study investigated the chemical constituents of Caesalpinia decapetala in the Fabaceae family. The chemical constituents were isolated and purified by chromatographies with silica gel, RP-C_(18), Sephadex LH-20, and preparative HPLC, and their structures were determined based on the spectroscopic data and physicochemical properties, as well as relevant references. Three pairs of new dibenzoxocin derivatives were isolated from 70% ethanol extract of C. decapetala and identified as protosappanoside A(1 a), isoprotosappanoside A(1 b), protosappanoside B(2 a), isoprotosappanoside B(2 b), protosappanoside C(3 a), and isoprotosappanoside C(3 b), respectively.

Effect of Medicated Serum Prepared with Chang'an Ⅰ Prescription on Sensitized Mast Cell Degranulation / 中国实验方剂学杂志

Objective:To observe the influence of Chang'an Ⅰ prescription drug-containing serum on IgE-mediated RBL-2H3 cell degranulation model， and explore the mechanism of Chang'an Ⅰ prescription in inhibiting RBL-2H3 activation degranulation and releasing inflammatory mediators with v-yes-1 Yanaguchi sarcoma viral related oncogene homolog （Lyn）/spleen tyrosine protein kinase （Syk）/mitogen-activated protein kinase （MAPK） signal pathway. Method:Preparation for Chang'an Ⅰ prescription serum. Animal group， SD male rats were randomly divided into Chang'an Ⅰ prescription serum high， medium， low dose， and blank control groups with 10 rats in each group. Dosage： 10 mL·kg-1 distilled water was given to blank control group， while Chang'an Ⅰ prescription serum high， medium and low dose groups were respectively given to the Chang'an Ⅰ prescription concentrated crude drug with concentration of 1.15，2.30，4.60 g·kg-1， respectively once a day for 7 days continuously and then blood was taken from aorta ventralis and centrifuged. Ketotifen as the positive control drug. Mast cells are counted with toluidine blue staining. Cellular release of β-aminohexose was detected by colorimetric method. Contents of MCT， TNF-α， MCP-1 and histamine were measured by enzyme-linked immunosorbent assay （ELISA） kits， Lyn/Syk/MAPK protein levels were detected by immunoblotting. Result:For cell activation and degranulation， compared with the blank control group， the model group had more cell degranulation （P<0.05）， compared with model group， the cell degranulation rate of each dose group of Chang'an Ⅰ prescription decreased （P<0.05）. The release rate of β-hexosamine in each dose group of Chang'an Ⅰ prescription decreased significantly （P<0.01）. For the release of active mediators， compared with the blank control group， the contents of histamine， MCT， TNF-α and MCP-1 all increased in the model group （P<0.01）， compared with the model group， the contents in each dose group of Chang'an Ⅰ prescription all decreased significantly （P<0.01）. Compared with the normal group， the phosphorylation levels of Lyn and Syk， extracellular regulatory protein kinase 1/2（ERK1/2）， c-Jun N-terminal kinase （JNK）， and mitogen-activated protein kinase p38 increased in the model group （P<0.05）. Compared with the model group， the Lyn， Syk and ERK1/2， JNK and p38 protein phosphorylation levels reduced in Chang'an Ⅰ prescription group （P<0.05）. Conclusion:Chang'an Ⅰ prescription drug-containing serum down-regulates the phosphorylation levels of proteins Lyn， Syk， and ERK1/2， JNK， and p38， inhibits RBL-2H3 cell activation and degranulation， reduces the release of cytokines and chemokines， such as histamine， MCT， TNF-α and MCP-1， it may be one of its mechanisms for treating IBS-D visceral hypersensitivity.

Study on Quality Standard Improvement of Rhizoma Begoniae from Guizhou / 中国药房

OBJECTIVE：To provide reference for improving the quality standard of Rhizoma Bego niae from Guizhou . METHODS：Five batches of Rhizoma Begoniae from Guizhou were collected ，and the microscopic characteri stics of the Rhizoma Begoniae powder were observed. According to the corresponding methods in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）， potent adenosine 50-triphosphate competitive phosphati - dylinositol-3-kinase/mammalian target of rapamycin inhibitors：discovery of compound 26（PKI-587），a highly effi cacious dual inhibitor Morpholine as a privileged structure ：a review on the me - dicinal chemistry and pharmacological activity of morpho - line containing bioactive molecules[J]. Med Res Rev ， qq.com 2019. DOI ：10.1002/med.21634. qualitative identification of Rhizoma Begoniae was conducted by TLC ，and the contents of moisture ，total ash and water-soluble extract in Rhizoma Begoniae were determined. The contents of rutin were determined by HPLC. RESULTS ：The powder of Rhizoma Begoniae medicinal materials was brown ，stone cells were square ，polygonal-like or irregular. There were many starch grains and few complex grains. The conduit ，calcium oxalate square crystal/cluster crystal were visible. The same fluorescence spots were found in the same location of TLC atlas of Rhizoma Begoniae control herb. The moisture ，total ash ，water-soluble extract contents were 10.15％-11.41％，8.70％-12.59％ and 16.91％-19.58％，respectively. The linear range of rutin were 18.47-147.8 μg/mL （r＝0.999 8）；RSDs of reproducibility ，intermediate precision and stability tests （8 h）were all lower than 3.0％；the average recoveries were 99.39％-100.29％（RSDs were 0.23％-2.59％，n＝3）；the contents of rutin in 5 batches of Rhizoma Begoniae were 0.102％-0.198％. CONCLUSIONS ：The contents of moisture and total ash shall not exceed 13.0％ and 14.0％ respectively， and the contents of water-soluble extract and rutin shall not be less than 15.0％ and 0.080％. The quality standard established in this study can be used for the quality control of Rhizoma Begoniae from Guizhou.

Simultaneous Determination of 8 Flavonoid Glycosides in Sedum bulbiferum by HPLC / 中国药房

OBJECTIVE：To establish a metho d for sim ultaneous determination of 8 flavonoid glycosides in Sedum bulbiferum . METHODS：HPLC method was adopted to determine the contents of kaempferol- 3-O-β-D-glucopyranoside-（1→2）-α-L-glucopy- ranoside-7-O-α-L-glucopyranoside（KGGR），kaempferol-3-O-β-D-glucopyranosyl-7-O-α-L-rhamnopyranoside（KGR），quercetin-3- O-α-L-rhamnose-7-O-α-L-rhamnoside（QRR），BulbiferumosideⅡ，kaempferol-3-O-（6-coumarinyl）-β-D-glucose-（1→2）-β-D-glu- cose-7-O-α-L-rhamnoside（KcGGR），kaempferol-3-O-（2-β-D-glucose）-α-L-rhamnose-7-O-α-L-rhamnoside（KGRR），kaempferol-3- O-α-L-rhamnoside-7-O-α-L-rhamnoside（KRR），kaempferol-3-O-（6″-acetyl-β-D-glucose）-7-O-α-L-rhamnoside（KaGR）in S. bulbi- ferum. The determination was performed on Waters CORTECS C 18 column with mobile consisted of acetonitrile - 0.1％ phosphoric acid water solution （gradient elution ）at the flow rate of 0.8 mL/min. The detection wavelength was set at 254 nm，and column temperature was 35 ℃. The sample size was 5 μL. RESULTS：The linear range of 8 constituents were 0.013-0.052，0.005-0.018， 0.008-0.031，0.010-0.042，0.009-0.038，0.008-0.030，0.009-0.037，0.032-0.130 μg，respectively（all r were not less than 0.999 0）. The limits of detection were 0.08，0.14，0.11，0.21，0.42，0.35，0.23，0.28 μg/mL，respectively. The limits of quantification were 0.25，0.47，0.38，0.69，1.40，1.17，0.77，0.93 μg/mL，respectively. RSDs of precision ，reproducibility and stability tests （24 h） were all lower than 3％（n＝6 or n＝7）. The average re coveries were 99.67％-104.20％（RSDs＝0.17％-1.59％，n＝6）. Average contents of above 8 constituents in 13 batches of samples were 0.893 8，0.312 6，0.490 8，0.964 9，0.751 2，0.502 2，0.606 2， 1.915 7 mg/g（n＝3）. CONCLUSIONS ： The method is simple， acourate and reproducible ， and can be used for simultaneous determination of 8 flavonoid glycosides in 才〔2016〕5677） S. bulbiferum .

Efficacy of letrozole in treatment of children with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency / 浙江大学学报·医学版

OBJECTIVE@#To assess the efficacy of letrozole in treatment of children with congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency (21-OHD).@*METHODS@#Twenty eight children, including 19 boys and 9 girls aged 4-10y, with CAH due to 21-OHD were enrolled in the study. At the first six months of study, all children received conventional treatment with hydrocortisone or fludrocortisone, then letrozole was added to original regimen. The height velocity (HV), difference between bone age and chronological age (BA-CA), height standard diviation score based on bone age (HtSDS ), predicted adult height (PAH), Tanner phase, sex hormone, and possible adverse reaction were evaluated and compared between those before and after letrozole treatment.@*RESULTS@#After 6 months of letrozole treatment, there was significant deceleration of HV, but it would recover soon. There was significant increase of HtSDS after 12 months of letrozole treatment ( < 0.05 or < 0.01), and significant changes in BA-CA after 18 months of letrozole treatment ( < 0.05). PAH of female children was significantly increased during letrozole treatment ( < 0.05), whereas PAH of male children was significantly increased 18 months after letrozole treatment ( < 0.05). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly increased, but did not meet the diagnostic criteria of central precocious puberty. Estradiol was significantly decreased ( < 0.01), but no changes in testosterone level was observed. During 24 months letrozole treatment, no hirsutism, severe acne, headache, bone pain, obesity, hypertension, rash and other adverse reactions were observed.@*CONCLUSIONS@#Letrozole can delay bone maturation and improve PAH, which can be used with conventional treatment for children with CAH due to 21-OHD, especially for those with high BA and low PAH.

Spectrum-effect Relationship of Anti-inflammatory Active Components from Nonvolatile Fraction of Blumea balsamifera Based on Gray Correlation Analysis / 中国实验方剂学杂志

Objective: To study the correlation between UPLC fingerprint of anti-inflammatory effect of active components from nonvolatile fraction of Blumea balsamifera, and to provide the basis for clarifying the anti-inflammatory material basis of B. balsamifera. Method: UPLC was used to establish fingerprint of nonvolatile fraction of 12 batches of B. balsamifera and their common fingerprint peaks were identified by UPLC-Q-TOF-MS.The corresponding pharmacodynamic data were obtained by auricle swelling and inflammation model mice induced by xylene, and spectrum-effect relationship was established by gray correlation analysis. Result: A total of 14 common peaks in nonvolatile fraction of B. balsamifera were established by UPLC fingerprint and 9 common peaks of them were identified.The correlation between UPLC fingerprint and the anti-inflammatory activity was from 0.717 1 to 0.550 5.The contribution of chemical compositions represented by each characteristic peak to the anti-inflammatory efficacy was in the order of peak 3 > peak 9 > peak 4 > peak 11 > peak 2 > peak 1 > peak 14 > peak 7 > peak 6 > peak 5 > peak 12 > peak 8 > peak 10 > peak 13, and the top two peaks with strong contribution to anti-inflammatory effect were peak 3 and peak 9, they were 3-O-caffeoylquinic acid and 3, 5-di-O-caffeoylquinic acid identified by contrast reference substances, respectively. Conclusion: The active substances in nonvolatile fraction of B. balsamifera are obtained through the study on the relationship between spectrum and efficiency, and the anti-inflammatory efficacy of the nonvolatile fraction is the result of combination of various components.It is clear that the caffeoylquinic acid derivates act as predominant anti-inflammatory active substance of nonvolatile fraction of B. balsamifera.

Study on the Quality Standards of Miao Medicine Oxalis corniculata / 中国药房

OBJECTIVE： To provide scientific basis for the utilization and development of Miao medicine Oxalis corniculata by promoting the quality standard of it. METHODS： Total of 12 batches of O. corniculata were collected from Guizhou， Anhui and Henan， etc. Microscopic characteristics of 12 batches of O. corniculata powder were observed. According to the corresponding methods in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）， TLC was used for qualitative identification [developing solvent was trichloromethane-methanol-formic acid （8 ∶ 1 ∶ 0.1， V/V/V）]， and the contents of moisture， total ash， acid insoluble ash and alcohol soluble extractive from 12 batches of O. corniculata were determined. The content of isovitexin was determined by HPLC. The determination was performed on Venusil XBP C18 （L） with mobile phase consisted of acetonitrile-0.1％ phosphoric acid solution  （15 ∶ 85， V/V） at the flow rate of 1 mL/min. The column temperature was 35 ℃， and the detection wavelength was set at 338 nm. The sample size was 10 μL. RESULTS： Microscopic observation showed that the powder was grayish brown to yellowish brown， with many non-glandular hairs and obvious fibrous pore. Results of TLC identification showed that the spots of the same color appeared in the corresponding positions of the test and the control chromatogram. The contents of moisture， total ash， acid insoluble ash and alcohol soluble extract from samples were 6.66％-12.13％， 9.16％-13.79％， 1.58％-4.63％ and 5.22％-15.79％， respectively. Results of HPLC method showed that the concentration of isovitexin showed a good linear relationship in the range of 5.20-78.3 μg/mL （r＝0.999 0）； RSDs of reproducibility （n＝9）， intermediate precision （n＝6） and stability （24 h， n＝6） tests were all lower than 2.0％； and the recovery rates were 97.54％-99.52％ （RSD＝0.74％， n＝6）； the contents of isovitexin in 12 batches of O. corniculata were 0.036％-0.144％ （n＝3）. CONCLUSIONS： Qualitative and quantitative identification methods of O. corniculate were established， which can be used as a reference for improving the quality standard of O. corniculata.

Effect of NEU3 on biological behaviors of human prostate cancer DU145 cells / 中国病理生理杂志

AIM:To explore the effects of neuraminidase 3 (NEU3) on the viability, invasion and apoptosis of human prostate cancer DU145 cells and the molecular mechanism.METHODS:The human prostate cancer DU145 cells were divided into blank control group and treatment group.The cells in treatment group were treated with either neuraminidase inhibitor DANA, or NEU3 small interfering RNA (siRNA) to knock down the expression of NEU3.The cell viability was measured by CCK-8 assay.The cell invasion ability was detected by Transwell assay.The effects of the treatments on the mRNA level of Bcl-2 were detected by q PCR.The effects of the treatments on the protein levels of matrix metalloproteinase 2 (MMP2) and apoptotic inhibitory protein Bcl-2 were determined by Western blot.Apoptosis of the cells was analyzed by flow cytometry.RESULTS:The protein level of NEU3 and the apoptotic rate in DANA group were not significantly different from those in blank control group.The viability of DANA-treated DU145 cells was increased, and the invasion ability, MMP2 protein level, and Bcl-2 mRNA and protein levels were all decreased in these cells, compared with blank control group.On the other hand, the levels of NEU3 protein and Bcl-2 mRNA and protein in NEU3 siRNA group were significantly decreased compared with blank control group, while the viability and apoptotic rate of the cells with NEU3 siRNA transfection were increased (P<0.05).However, the protein expression of MMP2 and the invasion ability of the cells were not significantly changed after NEU3 siRNA treatment.CONCLUSION:The inhibition of NEU3 in enzyme activity and expression decreases the viability, and enhances the apoptosis of human prostate cancer DU145 cells.However, it has no obvious effect on the invasion ability of DU145 cells.

Effects of active components of Epimedium, Astragalus and Radix Puerariae on expression of hepcidin in hippocampus CA3 in APPswe/PSldE9 double transgenic Alzheimer's disease model mice / 中国药理学通报

Aim To explore the effect of a combination of Astragalus, Epimedium and Pueraria on the expression of hepcidin in hippocampal CA3 region of APPswe/PSldE9 double transgenic AD model mice. Methods Thirty 10-month-old APPswe/PSldE9 double transgenic model mice were randomly divided into three groups; the compound group, the model group and the deferox (D F X) group, and ten 10-month-old C57BL/6J mice were as normal control group. Subsequently, the brain tissue of the mice was taken out, and the expression of hepcidin in the hippocampal CA3 region of each group of mice was detected by immunofluorescence combined with Real-time PCR and Western blot. Results Compared withnormal group, the mRNA expression of hepcidin was down-regulated inmodel group. Afterintragastric administrationof active components of Epimedium, Astragalus and Radix Puerariae and DFX, hepcidin expression levels increased significantly compared with those in APPswe/PSldE9 double transgenic AD model mice hippocampal CA3 area (P 0. 05). Conclusions The effective components of Astragalus, Epimedium and Radix Puerariae can up-regulate the expression of hepcidin, It is suggested that the effective components of Epimedium, Astragalus, and Radix Puerariae have important theoretical significance in the clinical treatment of Alzheimer's disease with iron overload.