Mechanisms of traditional Chinese medicine formulas and active ingredients in regulation of macrophage subsets involved in inflammation and repair of coronary heart disease / 中国中药杂志

Coronary artery disease(CAD) caused by atherosclerosis(AS) is a major contributor to the global burden of disease. The pathogenesis of CAD is complex, and the subset and function of cardiac macrophages are important factors affecting the occurrence and development of AS and the prognosis of CAD. Recent studies have shown that some traditional Chinese medicine(TCM) formulas and active ingredients can regulate macrophage subsets involved in the inflammation, injury, and repair process of CAD. This paper summarized the significant role of macrophages in AS and myocardial infarction. Based on the plasticity of macrophages, this paper elaborated that traditional Chinese medicine prevented and attenuated AS by regulating macrophage subsets, reducing the level of inflammatory factors, and promoting macrophage autophagy.Traditional Chinese medicine participated in the cardiac repair process after myocardial infarction by accelerating the recruitment of M2 macrophages, inhibiting the polarization of M1 macrophages mediated by glycolysis, inhibiting M1 macrophage-mediated cardiac nerve remodeling, and promoting M2 macrophage-mediated angiogenesis. In addition, in vitro studies on the regulation of macrophage subsets by the active ingredients of traditional Chinese medicine were also reviewed. It was pointed out that nuclear factor kappa B(NF-κB), adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt), chemokine(C-C motif) ligand 2/C-C chemokine receptor type 2(CCL2/CCR2) were the key targets and pathways for the regulation of macrophages by TCM.

Immune regulation mechanism of Saposhnikoviae Radix polysaccharide based on zebrafish model / 中国中药杂志

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1β and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1β, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.

Kunxian Capsule Extract Inhibits Angiogenesis in Zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the anti-angiogenic activity of Kunxian Capsule (KX) extract and explore the underlying molecular mechanism using zebrafish.@*METHODS@#The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization (hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 µg/mL of KX extract, respectively. After 24-h post exposure (hpe), mortality and malformation (%), intersegmental vessels (ISV) formation, and mRNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein (SIV) after 24 hpe.@*RESULTS@#The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV (P<0.01) and SIV formation (P<0.05). Besides, the mRNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT, thereby inhibiting the mRNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors (VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also down-regulated by KX treatment in zebrafish larvae.@*CONCLUSION@#KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VEGF pathway and showed promising potential for RA treatment.

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Relationship between Dining Place, Iodine Source, and Iodine Nutrition in School-Age Children: A Cross-Sectional Study in China / 生物医学与环境科学（英文）

OBJECTIVE@#This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children.@*METHODS@#School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables.@*RESULTS@#Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status.@*CONCLUSION@#Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.

Anti-osteoporosis mechanism of Panax quiquefolium L. based on zebrafish model and metabonomics / 药学学报

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

Clinical characteristics of liver function injury in patients with coronavirus disease 2019 / 中华传染病杂志

Objective:To investigate the incidence of liver injury in patients with coronavirus disease 2019 (COVID-19), and to explore its impact on the condition and prognosis of patients.Methods:The medical records of 67 patients with COVID-19 who presented with pneumonia hospitalized at Tongji Hospital, Huazhong University of Science and Technology from February 11 to March 28, 2020 were collected. The results of liver biochemistry and coagulation function test at admission were analyzed. Data were compared by chi-square test, analysis of variance or Kruskal-Wallis H test. Results:Among 67 patients, total bilirubin increased in seven (10.4%) patients, which was slightly abnormal, albumin decreased in 36(53.7%) cases, and was below 30 g/L in 15(22.4%) cases, alanine transaminase (ALT) and aspartate transaminase (AST) were elevated in 19(28.4%) and 12(17.9%) cases, respectively. A total of 22(32.8%) cases had elevated ALT and (or) AST. The incidences with elevated ALT and (or) AST in moderate and severe patients were 33.3%(10/30) and 26.9%(7/26), respectively. Five of 11 critical patients had elevated ALT and (or) AST. There was no significant difference among the three groups ( χ2=1.21, P=0.546). Abnormal alkaline phosphatase and (or) γ-glutamyl transpeptidase were observed in 11(16.4%) cases. The prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT) occurred in 10(14.9%) and 17(25.4%) patients, respectively, while most of them were slightly abnormal. Only one patient presented with prolongation of PT and APTT meeting the standard of liver failure. A total of 61.2%(41/67) and 65.7%(44/67) of cases showed increase of fibrinogen and D-dimer, respectively, and 28.4%(19/67) and 19.4%(13/67), respectively increased to an obvious extent. The albumin levels in moderate, severe and critical patients were (37.85±6.19) g/L, (32.96±4.33) g/L and (33.02±3.63) g/L, respectively, which were significantly different ( F=7.36, P=0.001). There were significant differences in PT, APTT, fibrinogen and D-dimer among the three groups ( F=3.22, 3.31, 4.06 and H=17.63, respectively, all P<0.05). Conclusions:COVID-19 only leads to mild liver injury and has only mild impact on liver function. The decrease of albumin level and the increase of fibrinogen and D-dimer may be early predicting indexes for the disease severity.

Observation of the growth and development of subchondral bone in rat condyles exposed to fluoride at the level of bone microarchitecture / 中华地方病学杂志

Objective:To observe the effect of fluoride on growth and development of bone microstructure of rats condyle subchondral bone (RCSB).Methods:Forty two 3-week-old SD rats (half male and half female) were fed adaptively for 1 week, and 3 females and 3 males were sacrificed and recorded as 0 month. The remaining rats were randomly divided into control group ( n = 18) and fluoride exposed group ( n = 18) according to their body weight (55 - 70 g), half male and half female. The fluoride exposed group was fed with 150 mg/L sodium fluoride (NaF) aqueous solution, and the control group was fed with tap water. The two groups of experimental animals were sacrificed at 3, 5 and 7 month, respectively, 6 rats in each group, half male and half female. The right mandibular condyle was separated, and Micro CT scanning was performed to detect the microstructure parameters of RCSB. Results:In fluoride exposed group (3 month), bone surface/tissue volume (BS/TV), bone surface/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), structure model index (SMI), connectivity, connectivity density (Conn.D) and total porosity of female rats were significantly different from those of male rats ( t = - 5.10, - 5.58, 4.52, - 4.32, - 4.03, - 2.81, - 6.71, - 3.32, P < 0.05). There was no significant difference in each index between female and male rats in fluoride exposed group (5, 7 month, P > 0.05). Conclusion:In chronic fluorine exposure bone environment, the RCSB bone microarchitecture of male and female rats is different with time, showing the tendency of fluoride injury that the bone changes of female rats are slowed and the bone changes of male rats are active.

Comparative study on fluoride accumulation in hard tissues of rats with chronic drinking-water-borne fluorosis / 环境与职业医学

Background A large number of studies on fluoride-induced systemic bone damage have been reported previously, but there is little understanding of the characteristics of fluoride accumulation in jawbone. Jawbone is homologous to the other bone tissues in the body, and is an indispensable and important frame structure in the oral cavity. Objective To study fluoride accumulation and its change trends in teeth, jawbone, and femur of SD rats with chronic drinking-water-borne fluorosis. Methods A total of 144 three-week-old SD rats, half male and half female, were randomly divided into two groups, a normal control group and a fluoride group. The rats in the normal controlgroup drank purified water disinfected and filtered from Guizhou, and the water contained 0.08 mg·kg−1 fluoride which was lower than the national water quality standard at 1 mg·kg−1. The rats in the fluoride group were fed with sodium fluoride (NaF) solution with a concentration of 150 mg·L−1. At 3, 5 and 7 months of the fluoride exposure, the levels of fluoride in urine, blood, teeth, jawbone, and femur were measured by fluoride ion electrode method. Results There was no sex difference in fluoride content in different biological samples of rats in the fluoride group and the normal control group (all P>0.05). After 3 months of fluoride exposure, the rats in the fluoride group showed dental fluorosis of grade II, and higher levels of fluoride ion in blood and urine than the normal control group (all P<0.05), indicating that the rat model of fluoride drinking-water-borne chronic fluorosis was successfully replicated. In the normal control group, the levels of fluoride in femur remained stable; at the end of 3 months, the levels of fluoride in jawbone and teeth were (1097.36±470.34) and (453.09±173.43) mg·kg−1 respectively, and at the end of 7 months, the levels of fluoride in jawbone and teeth were (2113.18±634.49) and (1604.80±160.43) mg·kg−1 respectively. Both jawbone and teeth showed a positive temporal effect of increasing fluoride accumulation (P<0.05). After continuous fluoride feeding, the fluoride levels in jawbone, teeth, and femur of rats in the fluoride group were (3145.02±765.82), (1550.20±77.73), and (3640.55±699.42) mg·kg−1 after 3 months, and (8420.36±1728.56), (4702.08±1417.06), and (6091.99±1384.97) mg·kg−1 after 7 months. The three kinds of hard tissues all showed a positive temporal effect of increasing fluoride accumulation (P<0.05), and the cumulative increas was large than that in the normal control group. Among them, jawbone fluorine increased most. At the end of 5 months, the levels of fluoride in jawbone, femur, and teeth were (6485.02±2141.98), (4914.99±1529.41), and (3365.21±1462.27) mg·kg−1 respectively, and the levels of fluoride in jawbone was much higher than those in femur and teeth (P<0.05). Conclusion Hard tissues such as bones and teeth are fluorine sensitive tissues. Compared with femur, jawbone showed significantly high fluoride accumulation, while teeth show relatively lagging fluoride accumulation.

Association of blood lead and blood selenium with serum high-sensitivity C-reactive protein among Chinese adults aged 19 to 79 years / 中华流行病学杂志

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.

Genetic Analysis of Thalassemia in 22 940 Pregnant Women in Xiangxi Tujia and Miao Autonomous Prefecture / 中国实验血液学杂志

OBJECTIVE@#To investigate the incidence and types of thalassemia in Xiangxi Tujia and Miao Autonomous Prefecture.@*METHODS@#Automatic capillary electrophoresis was used to screen the thalassemia phenotypes of 22 940 blood samples of pregnant women and puerperants collected in our hospital and some other medical institutions in the prefecture during 2017-2019, among which there were 3 356 cases of Tujia ethnicity, 2 821 cases of Miao ethnicity, and 2 233 cases of Han ethnicity included, whose ethnicity were indicated. The samples with positive result would undergo further genetic testing.@*RESULTS@#There were 2 314 cases of suspicious thalassemia were screened from 22 940 cases by the electrophoresis, thus the positive rate was 10.1% (hematological phenotypes from some other institutions were not included). Specifically, there were 1 706 cases with HBA2 less than 2.5%, 255 cases with HBA2 ranged from 2.5% to 3.5%, which displayed abnormal hematology (MCV or/and MCH) or other abnormal bands, and 353 cases with HBA2>3.5%. There were 436 suspected positive patients in 2 314 suspicious samples received further thalassemia gene testing in our hospital, among them 48 cases were diagnosed with α-thalassemia, 85 cases with β-thalassemia, and 2 cases as compound type. The positive diagnosis rate of α-thalassemia gene test was 11.0%, β-thalassemia was 19.4%, and positive pregnant women was 31.0%.@*CONCLUSION@#The positive rate of thalassemia screening in Xiangxi Autonomous Prefecture is roughly the same as that in other regions of Hunan. The positive predictive value of β-thalassemia screening is as high as 86%. Compared with the missed screening data, it is recommended to use hematology (MCV, MCH) method combined with capillary hemoglobin electrophoresis for thalassemia screening.

Quality value transfer of substance benchmarks in Sanpian Decoction / 中国中药杂志

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.

Application progress on taste evaluation methods for oral preparations / 中国中药杂志

Taste is an important factor affecting the medicinal properties of oral preparations and patient compliance with medication, and also an important evaluation index for oral preparation design and clinical application. How to characterize the taste objectively, accurately, simply, and efficiently is a bottleneck problem that restricts the taste design, development, and utilization of oral preparations. At present, the commonly used taste assessment methods for oral preparations are traditional human taste panel, electronic tongue, animal preference test, in vitro release study, and electrophysiological test. The traditional human taste panel is the first choice for taste evaluation, but it is limited by poor subjectivity and reproducibility. Therefore, despite some limitations, the other four taste assessment methods have been applied in the pharmaceutical industry as auxiliary methods. This study reviewed the detection principles, applicability, advantages, and disadvantages of the above methods to provide references for the taste correction research and taste assessment of oral preparations, improve patient compliance and the competitiveness of oral preparation products in the industry, and promote the development of oral preparation technologies.

Meta analysis of the effect of pre-transfusion prophylactic medication on the incidence of adverse reactions to blood transfusion / 中国输血杂志

【Objective】 To systematically evaluate the correlation between pretransfusion prophylactic medication and the incidence of adverse reactions to blood transfusion(ARBT) by Meta analysis. 【Methods】 The relevant literature concerning the effect of pretransfusion prophylactic medication on the incidence of ARBT was searched via Pubmed, Embase, Cochrane Library, CNKI, WanFang Data, and VIP databases, with the date duration from database creation to May 9, 2021. The literature was independently screened by two researchers according to the inclusion and exclusion criteria, relevant data information was extracted, quality evaluation was performed, and Meta analysis was performed using RevMan 5.3 software. 【Results】 A total of 36 publications were finally included, involving 137 996 transfusion recipients, of which 62 581 were administered medication before transfusion while 75 415 not. And1742 patients experienced ARBT. Meta analysis results showed that the incidence of ARBT in the pre-transfusion medication group was not statistically different from that in the non-medication group {[RR=0. 88, 95% CI(0.76, 1.01), P>0.05]}, the incidence of febrile reactions was lower in the pre-transfusion group than in the control {[RR=0. 72, 95% CI(0.61, 0.86), P0.05] vs [RR=0. 24, 95% CI(0.03, 2.13), P>0.05]. Pre-transfusion use of dexamethasone, isoproterenol, and niclosamide had no preventive effect on ARBT, i. e. [RR=0. 91, 95% CI(0.79, 1.04), P>0.05] vs [RR=0. 83, 95% CI(0.68, 1.01), P>0.05] vs [RR=1.21, 95% CI(0.69, 2.10), P>0.05]. 【Conclusion】 The incidence of ARBT in the pre-transfusion prophylaxis group was not significantly different from that in the control without considering the patient's history of transfusion, history of ARBT, and use of leukocyte-deleted blood products. The incidence of febrile reactions in the pre-transfusion medication group was lower than that in the control, and further studies in larger randomized controlled trials of higher quality still need to be established due to the suboptimal quality of the included literature and study size. Strictly grasping the indications for blood transfusion, strengthening the monitoring and awareness of ARBT, and using life-saving drugs rationally remain the key clinical concerns.

Simultaneous determination of 10 components in Guanxinshutong capsules by quantitative analysis of multi-components by single marker / 药学学报

This study establishes a quantitative analysis of multi-components by single marker (QAMS) method for the simultaneous determination of gallic acid, sodium danshensu, protocatechuic acid, protocatechuic aldehyde, vanillin, rosmarinic acid, salvianolic acid B, eugenol, cryptotanshinone and tanshinone IIA in Guanxinshutong capsules (Bambusae Concretio Silicea, Salvia miltiorrhiza, clove, borneol, Bambusae Concretio Silicea) by HPLC. Sample was loaded onto an Agilent C18 (ZORBAX Extend-RP C18, 250 mm × 4.6 mm, 5 µm) column and eluted with methanol-0.4% aqueous formic acid solution as a flow phase gradient, flow speed 1.0 mL·min-1, detection wavelength 280 nm, column temperature 35 ℃ and sample intake of 5 µL. Using protocatechuic acid as the internal reference, a relative correction factor was calculated and the durability was investigated, and the content of 10 components was calculated by QAMS and external standard method (ESM). The results show that the specificity, linear relationship, precision, repeatability, and stability of the 10 components were good. The average recovery was 98.20%-103.47% and RSD was 1.26%-2.84%. The relative positive factors and contents of the other nine components were calculated as gallic acid (0.759, 227.381), sodium tanshinol (3.630, 3.283), protocatechualdehyde (0.185, 0.150), vanillin (0.532, 65.213), rosmarinic acid (4.240, 1.035), salvianolic acid B (3.245, 18.204), eugenol (1.729, 9.265), cryptotanshinone (0.691, 1.449), and tanshinone ⅡA (0.702, 1.939). The results of QAMS were consistent with ESM analysis, and the relative error was between -3% and 3%. This method is stable and reliable, and can be used for the determination of 10 components in Guanxinshutong capsules.

An integrated strategy toward comprehensive characterization and quantification of multiple components from herbal medicine: An application study in Gelsemium elegans / 中草药·英文版

Objective: To develop a powerful integrated strategy based on liquid chromatography coupled with mass spectrometry (LC-MS) systems for the comprehensive characterization and quantification of multiple components of herbal medicines. Methods: Firstly, different mobile phase additives, analysis time, and MS acquisition modes were orthogonally tested with liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) in order to detect as many components of Gelsemium elegans as possible with high peak intensity. Secondly, several data mining strategies, including database searching, diagnostic ion filtering and neutral loss filtering, were utilized to perform chemical profiling. Subsequently, this study focused on the quantification and validation of the performance of a liquid chromatography-triple mass spectrometry (LC-QqQ/MS) assay based on derivative multiple reaction monitoring (DeMRM). Results: A total of 147 components from G. elegans were characterized, among them 116 nontarget components were reported for the first time. A sensitive and reproducible LC-QqQ/MS method was successfully developed and validated for the simultaneous relative quantification of 41 components of G. elegans. This LC-QqQ/MS method was then applied to compare the contents of components in the roots, stems and leaves. Conclusion: The present integrated strategy would significantly contribute to chemical studies on herbal medicine, and its utility could be extended to other research fields, such as metabolomics, quality control, and pharmacokinetics.

Free peroneal artery perforator flap designed by vascular localization with three-dimensional CT angiography for repairing soft tissue defects of the dorsal forefoot / 中华创伤杂志

Objective:To investigate the surgical method and clinical effect of the free peroneal artery perforator flap designed by vascular localization with three-dimensional CT angiography（3D-CTA）in repairing soft tissue defects of the dorsal forefoot.Methods:A retrospective case series study was conducted to analyze the clinical data of 17 patients with soft tissue defects of the dorsal forefoot admitted to Hospital of the 80th Group Army of PLA from February 2015 to January 2019，including 11 males and 6 females，aged from 16 to 65 years［（39.2±9.7）years］. The area of soft tissue defects ranged from 3.0 cm×2.0 cm to 10.0 cm×7.0 cm，and the size of skin flap was from 3.5 cm×2.5 cm to 10.5 cm×7.5 cm. Preoperative 3D-CTA was performed to select the appropriate perforator vessels，and a personalized skin flap was designed according to the examination results and wound conditions. Of all，10 patients were repaired with the peroneal perforator flap at the first stage，and 7 patients grafted with peroneal perforator flap with wound expansion in the second stage. The perforator diameter，vertical distance from the starting point of the perforator to the tip of the lateral malleolus and horizontal distance from the starting point of the perforator to the outer edge of the lower leg were compared between preoperative 3D-CTA and actual intraoperative measurements. The survival of the flap and occurrence of the vascular crisis were observed after operation. The foot function was assessed with the American Orthopedic Foot and Ankle Society（AOFAS）ankle hindfoot score preoperatively and at postoperative 6 months. Six months after operation，effect of flap repair was evaluated by using flap satisfaction score and flap sensory function measured by the criteria established by British Medical Rresearch Council（BMRC）. Incision healing and motor function of the donor area were detected.Results:All patients were followed up for 6-12 months［（9.6±2.3）months］. There was no statistically significant differences in perforator diameter，vertical distance from the starting point of the perforator to the tip of the lateral malleolus and horizontal distance from the starting point of the perforator to the outer edge of the lower leg between preoperative 3D-CTA and actual intraoperative measurements（ P>0.05）. All flaps survived without vascular crisis. Six months after operation，a higher AOFAS ankle hindfoot score［（84.0±7.9）points］was found when compared to that preoperatively［（51.3±8.2）points］（P<0.05），with excellent results in 12 patients and good results in 5 patients. At 6 months after the operation，the thickness of the flap was flush with the surrounding skin，which did not affect the wearing of shoes；the thickness of the flap was level with the surrounding skin but did not affect the wearing of shoes. The repair effect was satisfactory with the flap satisfaction score of（8.7±2.3）points.Based on the criteria established by BMRC，the sensory function of the flap continued to improve，including 10 patients reaching the level of S 3-S 4 with the two-point discrimination of（10.2±2.0）mm and 7 patients reaching the level of S 2. All incisions at the donor area were healed well without obvious scar contracture or motion limitation. Conclusions:For soft tissue defects of the dorsal forefoot，3D-CTA assisted vascular localization is able to have individualized and precise design of peroneal artery perforator flap preoperatively to assist rapid and accurate skin flap cutting and accelerate defect healing and functional recovery in the dorsal foot. Moreover，the free peroneal artery perforator flap has advantages of high patients' satisfaction，with minor trauma on donar site or without damaging the main artery.

Cytokine release assessment:a good de-risk approach to bi-specific T-cell engagers in non-clinical development / 中国药理学与毒理学杂志

Bi-specific T-cell engagers (BiTEs) show great clinical outcomes for anti-cancer purposes. However, potential cytokine release syndrome (CRS) is notorious to all BiTEs. The mechanism underlying CRS is still not fully known, even though such toxicities are considered to be cytokine release related. Assessment of CRS is a key to non-clinical de-risk programs for BiTEs therapeutic development. In the present review, possible mechanisms are discussed, especially factors contributing to CRS develop?ment. T cell activation may be just an initiation of the CRS cascade, and other cell types can greatly contribute to CRS, such as a chain reaction triggered by downstream B-cells, monocytes, and endothe?lium cells. A non-clinical de-risk program can be designed based on these components in the CRS cascade. Combination of in vitro cytokine release assay, and in vivo mouse and non-human primates studies should be reliable enough to predict and mitigate CRS risk in the clinics. Further more, a good de-risk program should be able to provide ranking for candidates for further development and provide enough confidence to select a first-in-human dose.

Selection of q RT-PCR reference genes for Amomum tsaoko seeds during dormancy release / 中国中药杂志

Freshly collected seeds of Amomum tsaoko demonstrate obvious dormancy. Therefore, the selection of stable reference genes during seed dormancy release is very important for the subsequent functional research of related genes. In this study, ten commonly used reference genes(GAPDH, 40S, actin, tubulin, EIF4A-9, EIF2α, UBC, UBCE2, 60S, and UBQ) were selected as candidates for quantitative Real-time polymerase chain reaction(qRT-PCR) of the embryo samples of A. tsaoko at different dormancy release stages. Three kinds of software(BestKeeper, geNorm, and Normfinder) and the Delta CT method were used to evaluate the expression stability of the candidate reference genes, and the RefFinder online tool was employed to integrate the results and generate a comprehensive ranking. The results showed that the expression levels of the ten candidate reference genes differed greatly in different embryo samples. GAPDH and UBC had high expression levels, as manifested by the small Ct values. GeNorm identified 40S and UBCE2 as the most stable genes. NormFinder ranked EIF2α as the most stable gene and UBC as the least stable gene. UBCE2 was found to be the most stable gene and actin the least stable one by BestKeeper. Delta CT analysis suggested that the expression of 40S was most stable. UBCE2 was recommended as the most stably expressed gene by RefFinder. Thus, UBCE2 is the ideal reference gene for qRT-PCR analysis of A. tsaoko seeds at different dormancy release stages. The results may lay a foundation for analyzing the expression of related genes during seed dormancy release of A. tsaoko.

Mechanism of puerarin reversing SH-SY5Y cell injury induced by Aβ_(1-42) based on proteomics / 中国中药杂志

Puerarin has the anti-Alzheimer's disease (AD) activity,which can reverse nerve injury induced by Aβand inhibit neuronal apoptosis.However,its potential pharmacodynamic mechanism still needs to be further researched.The occurrence and development of AD is due to the change of multiple metabolic links in the body,which leads to the destruction of balance.Puerarin may act on multiple targets and multiple metabolic processes to achieve therapeutic purposes.Quantitative proteomic analysis provides a new choice to understand the mechanism as completely as possible.This research adopted SH-SY5Y cells induced by Aβ_(1-42)to establish AD cell model,and Aβimmunofluorescence detection showed that Aβdecreased significantly after puerarin intervention.The mechanism of puerarin reversing SH-SY5Y cell injured by Aβ_(1-42)was further explored by using label-free non-labeled quantitative technology and Western blot detection based on bioinformatics analysis result.The results showed that most of the differential proteins were related to biological processes such as cellular component organization or biogenesis,cellular component organization and cellular component biogenesis,and they mainly participated in the top ten pathways of P value such as pathogenic Escherichia coli infection,m TOR signaling pathway,regulation of autophagy,regulation of actin cytoskeleton,spliceosome,hepatocellular carcinoma,tight junction,non-small cell lung cancer,apoptosis and gap junction.Annexin V/PI flow cytometry and TUNEL were used to detect apoptosis,and the results showed that Aβdecreased significantly and the rate of apoptosis decreased significantly after puerarin intervention.Western blot analysis found that the protein expression level of autophagy related protein LC3Ⅱwas up-regulated after Aβinduction,and the degree of this up-regulation was further enhanced in puerarin intervention group.The trend of the ratio of LC3Ⅱ/LC3Ⅰamong groups was the same as the protein expression level of LC3Ⅱ，the protein expression level of p62 in the control group,AD model group and puerarin intervention group decreased successively.Protein interaction network analysis showed that CAP1 was correlated with TUBA1B,HSP90AB2P,DNM1L,TUBA1A and ERK1/2,and the correlation between CAP1 and ERK1/2 was the highest among them.Western blot showed that the expressions of p-ERK1/2,Bax and CAP1 were significantly down-regulated and the protein expression level of Bcl-2 was significantly up-regulated after puerarin intervention.Therefore,puerarin might improve the SH-SY5Y cells injured by Aβ_(1-42)through the interaction of multiple biological processes and pathways in cells multiple locations,and CAP1 might play an important role among them.