Longitudinal study on catch-up growth in preterm infants with small for gestational age at corrected ages 0-24 months / 中国当代儿科杂志

OBJECTIVES@#To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants.@*METHODS@#A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared.@*RESULTS@#The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively.@*CONCLUSIONS@#SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.

Lignans from stems and leaves of Cephalotaxus fortunei (Ⅱ) / 中国中药杂志

The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-β-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.

Epidemiological characteristics of hand, foot and mouth disease in Nanping City, Fujian Province from 2012 to 2021 / 中国热带医学

@#Abstract: Objective　To analyze the epidemic characteristics of hand, foot and mouth disease (HFMD) in Nanping City, Fujian province and to provide the basis for formulating effective prevention and control measures as well as evaluating the efficacy of prevention and treatment. Methods　Descriptive epidemiological method was used to analyze the incidence data of HFMD in Nanping City from 2012 to 2021. Results　A total of 49 231 cases of HFMD were reported in Nanping City from 2012 to 2021. The incidence fluctuated greatly over the 10-year period, ranging from 76.10/100 000 to 308.93/100 000, with an average incidence of 184.99/100 000 per year. The overall incidence and the number of cases showed a fluctuating downward trend over time, but the incidence was high in the next year, and there were statistically significant differences in the incidence rates between different years(χ2=8 169.176, P<0.001). There were significant regional differences in the incidence, the top three average annual incidence rates were: Guanze County (370.76/100 000), Zhenghe County (295.31/100 000) and Wuyishan City (250.31/100 000). There were two peaks of HFMD incidence each year, with the first occurring in May and June and the second occurring in September and October. The incidence rate was higher among males (215.86/100 000) than females (152.93/100 000), and males were more susceptible than females (RR=1.412, 95%CI=1.387-1.438). The cases were mainly aged 0-4 years, accounting for 86.25% (42 461/49 231) of all cases, and the incidence rate gradually decreased with increasing age (χ2trend=570,105.801, P<0.001). The majority of cases (85.22%, 41 953/49 231) occurred in children living in scattered areas, followed by children in kindergartens (12.39%, 6 101/49 231). The etiological results showed a total of 3 476 laboratory-confirmed cases, and the proportion of three (classes) of enterovirus positivity varied each year, with different pathogen compositions showing statistical significance (χ2=584.613, P<0.001). In addition to the years 2015-2017, during which Cox A16 and EV71 were the dominant strains, other years were dominated by other enteroviruses, with EV71 being the main type in severe and fatal cases of HFMD in Nanping City. Conclusion　Nanping City should strengthen health education for children living in the diaspora and in day-care centers, enhance surveillance of epidemics and pathogenology, improve vaccination rates against EV71, focus on the detection and typing of other enteroviruses, and implement effective prevention and control measures for HFMD.

The effect and mechanism of formononetin on alleviating no-reflow after myocardial ischemia and reperfusion by up-regulating the PI3K/Akt/eNOS signal pathway activated by GPER / 药学学报

To investigate the cardioprotective effect of formononetin (FMN) on no-reflow (NR) after myocardial ischemia-reperfusion and its molecular mechanism based on integrated pharmacology and experimental verification, firstly, human breast cancer MCF-7 cells and myocardial NR rats were used to confirm the estrogenic activity and the effect of alleviating NR of FMN, respectively. Male SD rats were divided into Sham, NR, FMN (20 mg·kg-1) and sodium nitroprusside (SNP, 5.0 mg·kg-1) groups, which were administered once a day for one week, the experiment was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TCM-LAEC2019095). The pharmacological analysis and in vivo study of NR rats were integrated to reveal the mechanism of FMN improving NR. The results showed that FMN had estrogenic effect and reduced NR by improving cardiac structure and function, reducing NR, ischemic myocardial area and pathological injury of cardiomyocytes. Integrated pharmacology predicts that the mechanism of FMN improving NR is mainly related to phosphatidyinositol-3-kinase-protein kinase B (PI3K-Akt) signal pathway. Phytoestrogens play a role in cardiovascular protection mainly by activating G protein-coupled estrogen receptor (GPER). GPER is also an important regulator in the upstream of PI3K-Akt signaling pathway. This study found that FMN can significantly activate GPER, p-PI3K, p-Akt and phospho-endothelial nitric oxide synthase (p-eNOS). It has good binding ability with GPER and eNOS protein. In this study, through the integration of pharmacology and experimental evaluation, it is revealed that FMN activates PI3K/Akt/eNOS signal pathway by activating GPER, thus significantly improving NR.

Q-marker prediction of resin ethanol extract of Gegen Qinlian Decoction based on characteristic spectrum and network pharmacology / 中国中药杂志

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the "five principles" of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Virtual screening of anti-inflammatory components in Blumea balsamifera(L.)DC.And effect of ergosterol peroxide on NF-kB Signaling pathways / 中国药理学通报

Aim To target the key proteins of TLR4 signaling pathway to sereen the compounds of Blumea baisamifera ( L.) DC.in order to explore the anti-in- flammatorv active components and the mechanism of action of key proteins targeting TLR4 signaling pathway in Blumea balsamifera( L.) DC.Methods The effects of ergosterol peroxide ( EP) on cell activity, LPS in¬duced inflammatory factor secretion and NF-kB related protein expression were detected by MTT, EL1SA, Western blot and Subcellular Structural Localization.Results The results showed EP, (3-sitosterol, 16- kaurene, carosterol, luteolin, ergosterol, hyperin and genkwa had more optimal interconnection score.EP (2.3 x 10"5 ~ 9.3 x 10 5 mol • L"1) inhibited the degradation and phosphorylation of inflammatory pro¬tein IkB and phosphorylation of NF-kB p65 down¬stream of TLR4 signaling pathway induced by LPS in BAW264.7 cells,and further inhibit the entrv of NF-kB p65 into the nucleus, thus inhibiting the secretion of cytokines IL-lp and 1L-6.Conclusions The antiin¬flammatory components of Blumea balsamifera ( L.) DC are identified by molecular docking technology and ac-tivity detection technique, and the anti-inflammatory action anrl mechanism of EP as active substances are e- luci dated.

Tetrahydropalmatine alleviated diabetic neuropathic pain by inhibiting activation of microglia via p38 MAPK signaling pathway / 中国中药杂志

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.

Pathological Mechanism of HSOS in Rats Induced by Different Doses of Monocrotaline / 中国实验方剂学杂志

ObjectiveTo observe the pathological changes of hepatic sinusoidal obstruction syndrome （HSOS） induced by different doses of monocrotaline （MCT） in rats， investigate the dose and duration of modeling， and elucidate the mechanism. MethodA total of 72 male SD rats were randomized into normal group （n=12）， and low-， medium-， and high-dose MCT groups （n=20 per group， 80，120，160 mg·kg-1， respecctively）. In the model groups， different doses of MCT were intragastrically administered to induce the HSOS in rats. After 48 h and 120 h separately， rats in each group were sacrificed and sampling was performed. The survival rate of rats in each group was calculated， and the body weight， liver weight， and and serum liver function indexes of the rats were examined. The histopathological changes of the liver were observed based on scanning electron microscopy， hematoxylin and eosin （HE） staining， and Sirius red （SR） staining. Glutathione S-transferase （GST） activity， total superoxide dismutase （T-SOD） activity， and malondialdehyde （MDA） content of liver tissue homogenate were measured with microplate method. The expression of liver tissue-related indexes was detected by real-time polymerase chain reaction （PCR）， Western blot， and immunohistochemistry. ResultThe activity of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in MCT groups rose with the increase in MCT dose （P<0.05， P<0.01） compared with that in the normal group. With the extension of modeling time， the activity of serum ALT and AST in the low-dose group decreased （P<0.01）， while the activity of them in the medium-dose and high-dose groups increased （P<0.01）. HE staining showed that hepatocyte necrosis， inflammatory cell infiltration， and erythrocyte accumulation in MCT groups. Electron microscopy demonstrated that fenestrae of liver sinusoidal endothelial cells widened and the sieve plates disappeared. Morever， the injury was worsened with the increase in MCT dose. In addition， the expression of CD44 in MCT groups was significantly reduced compared with that in the normal group （P<0.05， P<0.01）. SR staining showed that no positive staining was found in model groups after 48 h， while collagen deposition in portal areas and liver sinusoids could be seen in model groups after 120 h. MCT groups showed increase in MDA content and GST activity and decrease in T-SOD activity compared with the normal group， particularly the medium-dose and high-dose groups （P<0.01）， and the changes were dose-dependent after 120 h （P<0.01）. The protein expression of CD68 （pro-inflammatory macrophage marker） was raised with the increase in dosage， which was consistent with the results of immunohistochemistry （P<0.01）， while CD163 （anti-inflammatory macrophage marker） protein and mRNA expression was significantly decreased with the increase in dosage （P<0.01）. Western blot results showed that the expression of phosphorylated nuclear factor-κB/nuclear factor-κB （p-NF-κB/NF-κB） and phosphorylated protein kinase B/protein kinase B （p-Akt/t-Akt） was significantly increased in medium-dose and high-dose MCT groups （P<0.05，P<0.01）. The protein expression of α-smooth muscle actin （α-SMA） in liver tissues in MCT groups was significantly increased over time and with the increase in dose， and the mRNA expression of α-SMA， collagen type I α1 （Col1a1）， and collagen type Ⅳ α1 （Col4a1） showed the same trend （P<0.05， P<0.01）. The results of TUNEL staining showed that apoptotic cells were increased with the rise of MCT dose， while B-cell lymphoma-2（Bcl-2） /Bcl-2 associated X protein （Bax） was remarkably decreased （P<0.01）. ConclusionHSOS in rats induced by intragastric administration of different doses of MCT was aggravated with the increase of dosage. In the low-dose （80 mg·kg-1） MCT group， the liver healed spontaneously over time. However， liver damage caused by MCT of 120 mg·kg-1 and 160 mg·kg-1 aggravated over time， and even fibrosis and death occurred. The pathological mechanism of MCT-induced HSOS in rats may be that MCT triggered intense oxidative stress in liver tissue， thus activated pro-inflammatory macrophages to secrete large amounts of inflammatory factors， and further activated the NF-κB/Akt signalling pathway， leading to severe cell damage and death.

Effect of Baofeikang Granule on Pulmonary Fibrosis in Rats by Regulating Wnt/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the intervention effect of Baofeikang granule （BFK） on the rat model of pulmonary fibrosis through the Wnt/β-catenin signaling pathway. MethodAfter adaptive feeding for one week， 50 healthy rats were randomly divided into a blank group （n=8） and an experimental group （n=42）. After anesthesia， the rats in the experimental group were injected with bleomycin sulfate solution （5 mg·kg-1） into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7th day after modeling， one of the remaining 33 rats alive was randomly removed， and the other 32 model rats were assigned into a model group （n=8）， a prednisone acetate （1.17 mg·kg-1） group （n=8）， a low-dose BFK （13.59 g·kg-1） group （n=8）， and a high-dose BFK （27.18 g·kg-1） group （n=8）. The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days， and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function， the scores of pathological changes and fibrosis， the levels of type Ⅰ collagen （Col Ⅰ） in lung tissues and hydroxyproline （HYP） in the serum， and the relative expression of Wnt3a and β-catenin protein in lung tissues were compared. ResultCompared with the blank group， the model group showed reduced pulmonary function indexes， such as forced vital capacity （FVC）， peak expiratory flow （PEF）， the resistance of lung （RL）， and dynamic compliance （Cdyn） （P<0.05， P<0.01）， severely damaged lung tissue morphology， massive formed continuous fibrous foci， increased fibrosis score （P<0.01）， elevated levels of Col Ⅰ in lung tissues and HYP in the serum （P<0.01）， and up-regulated expression of Wnt3a and β-catenin （P<0.01）. FVC， PEF， and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group （P<0.05， P<0.01）. Pathological changes were improved in the groups with drug intervention， and fibrosis scores were decreased as compared with the model group （P<0.05， P<0.01）. The scores in the BFK groups were lower than that in the prednisone acetate group （P<0.01）. The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group （P<0.05， P<0.01）. The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group （P<0.01）. The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group （P<0.01）. The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group （P<0.05）. The protein expression of β-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group （P<0.05， P<0.01）， and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group （P<0.01）. ConclusionBFK can relieve bleomycin sulfate-induced pulmonary fibrosis， reduce collagen deposition， improve pulmonary compliance， and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/β-catenin signaling pathway.

Fração de Ejeção do Ventrículo Esquerdo Aumentada, Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico / Increased, Decreased, or Stable Left Ventricle Ejection Fraction over Time in a Series of 626 Heart Failure Patients Receiving Medical Treatment

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III-IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

Effect of Geniposide on Liver Injury and Bile Acid Profile in Serum, Liver and Excrement of Rats / 中国实验方剂学杂志

Objective:To investigate the hepatotoxicity of different doses of geniposide on the liver of rats and the effects on bile acid profile in serum， liver tissue and feces. Method:The 60 Sprague Dawley rats， half male and half female， were randomly divided into 5 groups according to body weight： blank group and four different doses （50， 100， 200， 400 mg·kg^-1） geniposide groups， 12 rats in each group. The rats were treated by gavage once a day for 7 consecutive days， and the serum， liver and cecal contents were collected on the 8^th day of treatment. The activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and alkaline phosphatase （ALP）， the contents of albumin （ALB）， total bilirubin （TBIL）， total bile acid （TBA）， creatinine （Crea） and carbamide （Urea） were detected in each group. The sections of liver tissue were stained with hematoxylin-eosin（HE）， and the protein expressions of cytokeratin 7（CK7） and cytokeratin 19（CK19） were detected by immunohistochemistry. The protein expressions of CK7 and CK19 in the liver tissue were detected by Western blot. And the mRNA expressions of cholesterol 7<italic>α</italic>-hydroxylase （CYP7A1）， cholesterol 27<italic>α</italic>-hydroxylase （ CYP27A1） and cholesterol 12<italic>α</italic>-hydroxylase （CYP8B1） were detected by real-time PCR. The contents of 18 kinds of bile acids in serum， liver and cecal contents were determined by ultra-performance liquid chromatography-mass spectrometry（UPLC-MS）. Result:Compared with the control group， TBIL level in each dose of geniposide group was increasesd significantly （<italic>P</italic><0.01）. ALT， AST activity and TBA content in 400 mg·kg^-1 geniposide group were increased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）. HE staining showed that， compared with control group， there was bile duct reaction in the portal area and inflammatory cells infiltrate around bile duct in 200 mg·kg^-1 and 400 mg·kg^-1 geniposide groups， especially 400 mg·kg^-1. The expressions of CK7 and CK19 in liver tissue of 400 mg·kg^-1 geniposide group were significantly higher than those in the control group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the control group， the contents of glycoursodeoxycholic acid （GUDCA） and glycohyodeoxycholic acid （GHDCA） in liver tissue of 400 mg·kg^-1 geniposide group decreased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）， the contents of sodium taurochenodeoxycholate （TCDCA）， hyodeoxycholic acid （HDCA）， cholic acid （CA） and chenodeoxycholic acid （CDCA） in liver tissue increased significantly （<italic>P</italic><0.01）， the contents of glycocholic acid hydrate （GCA）， glycochenodeoxycholic acid （GCDCA）， glycodeoxycholic acid hydrate （GDCA）， glycocholic acid （GLCA）， tauroursodeoxycholic acid （TUDCA）， GUDCA， GHDCA， ursodeoxycholic （UDCA） and taurolithocholic acid （TLCA） decreased， the proportions of TCDCA， HDCA， CA， CDCA and deoxycholic acid （DCA） in liver tissue increased， the contents of GHDCA and lithocholic acid （LCA） in serum decreased significantly （<italic>P</italic><0.01）， while sodium taurohyodeoxycholate hydrate （THDCA）， taurocholic acid （TCA）， GCA， TCDCA， UDCA， CA， CDCA， DCA in serum decreased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）. The contents of CA， UDCA， CA， CDCA and DCA increased significantly （<italic>P</italic><0.05）， the ratio of CA/DCA increased significantly （<italic>P</italic><0.05）， and the ratio of CA and CDCA increased by 19.60% and 4.63%， respectively； Compared with the control group， the contents of all bile acids in cecal contents of 400 mg·kg^-1 were decreased， and the contents of GCA， UDCA， HDCA， GCDCA， GDCA， TLCA， GLCA， CDCA， DCA and LCA were decreased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）. In addition， real-time PCR results showed that the mRNA expressions of CYP7A1， CYP27A1 in the 400 mg·kg^-1 geniposide group were significantly higher than those in the control group （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:The 400 mg·kg^-1geniposide can cause obvious hepatotoxicity in rats， and the bile acid profile in liver， serum and excrement changes significantly， and the changes of the each bile acid in liver， serum and feces are different. However， the causal relationship between the gardenoside-induced liver injury and the changes in bile acid profile are<italic> </italic>not clear. It needs to be further studied.

Advances in pharmacological effects of ginsenoside on Alzheimer's disease / 中国药理学通报

Alzheimer's disease (AD) has become one of the major diseases that plague human health and seriously affect the quality of life of patients. Up to present there is no specific treatment drug for Alzheimer' s disease, which still needs research and development. Ginseng is an important traditional Chinese medicine in the prescription for treating of Alzheimer's disease, which contains saponins, polysaccharides, volatile components, proteins, vitamins, amino acids and other compounds. Saponins are the main active components, which have a good effect on improving learning and memory ability and preventing AD. In this paper, the effect and the mechanism of ginsenosides for treating AD are reviewed in order to provide ideas for developing ginsenosides into drugs with better clinical compliance and more effective treatment of AD.

Analysis of varieties and standards of Saxifragaceae medicinal plants used in Tibetan medicine / 中国中药杂志

On the basis of literatures and standards relating to Tibetan medicine, the varieties, origin, standards and efficacy of Saxifragaceae plant used in Tibetan medicine were summarized. According to the findings, 75 species(including varieties) in 8 genera of Saxifragaceae plants, involving 21 varieties, are used in Tibetan medicine. Among them, 9 commonly used varieties, namely Songdi, Sedi, Yajima, Aoledansaierbao, Jiansidawu, Saiguo, Katuer, Sangdi, Maoqinghong, are recorded in Chinese Pharmacopoeia, Ministry Standards for Tibetan Medicine, Tibetan Medicine Standards and other local standards, accounting for 42.9% of the total number of varieties. Tibetan names, Tibetan translation of Chinese names, as well as original plant of Tibetan medicine varieties are quite different in relevant Tibetan medicine standards and literatures, which resulted in common phenomena of synonym and homonym. The standards of most varieties only involve characters, and microscopic, physical and chemical identification, with low quality standards. Based on the results of the analysis, this paper suggests strengthening surveys on herbal textual research, resources and current utilization of Saxifragaceae plants used in Tibetan medicine, summarizing the varieties, establishing improved quality standards, and perfor-ming a comparative study on therapeutic material basis and biological activity of different original plants, in order to promote rational use of these medicinal plant resources, and ensuring the accuracy, safety, and effectiveness of clinical medication.

Preparation and characterization of biomimetic liposomes coated with erythrocyte membrane co-loading triptolide and celastrol / 药学学报

Drug combination can effectively enhance the anti-tumor effect, reduce the drug dose, and improve medication safety. The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo. Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f. Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect, but they are limited by poor water solubility and low tumor tissue delivery rate. In this study, a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology, particle size, potential, drug release, serum stability, and other properties. The immunogenicity, uptake behavior, and anti-cell proliferation ability of the biomimetic liposome was compared. All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (Chengdu, China). The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol (C+T/RBCm@Lip) in this study had an average particle size of 119.12 ± 2.78 nm and a spherical "core-shell" structure. The zeta potential value was -16.9 ± 1.2 mV, and the drug release behavior in vitro was slow. In addition, the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein, had good stability in serum, and could effectively avoid the recognition and clearance of macrophages, without causing immunogenicity in vivo. The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes, and the inhibitory effect on proliferation of HepG2 cells was enhanced. In conclusion, the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol, and could enhance the inhibitory effect on the growth of HepG2 liver cancer cells, providing a new idea for the anti-tumor application of Tripterygium wilfordii Hook f.

Research advances on the effect of ginsenoside Rg1 on angiogenesis and vascular protection / 药学学报

Ginsenoside Rg1 is one of the most important active components of the "king of herbs" Panax ginseng, which is an important angiogenic protective agent. The research results have shown that Rg1 has a wide range of cardiovascular pharmacological effects in vivo and in vitro, mainly through promoting the proliferation of smooth muscle cells, inhibiting endothelial cell aging, antioxidant stress, inhibiting inflammatory response, activating key factors of angiogenesis, improving vasodilation and other ways. Many miRNAs participate in the process of Rg1 promoting angiogenesis, mediate the regulation of the specific expression of downstream related targets to promote angiogenesis and vascular remodeling, and have the potential to become new clinical biomarkers and therapeutic targets. New preparation technologies and materials are used to make up for the weakness of Rg1's blood-brain barrier permeability, and further promote and enrich the clinical application of Rg1.

Identification of key genes for type 1 diabetes mellitus by network-based guilt by association

SUMMARY OBJECTIVE This study aimed to propose a co-expression-network (CEN) based gene functional inference by extending the "Guilt by Association" (GBA) principle to predict candidate gene functions for type 1 diabetes mellitus (T1DM). METHODS Firstly, transcriptome data of T1DM were retrieved from the genomics data repository for differentially expressed gene (DEGs) analysis, and a weighted differential CEN was generated. The area under the receiver operating characteristics curve (AUC) was chosen to determine the performance metric for each Gene Ontology (GO) term. Differential expression analysis identified 325 DEGs in T1DM, and co-expression analysis generated a differential CEN of edge weight > 0.8. RESULTS A total of 282 GO annotations with DEGs > 20 remained for functional inference. By calculating the multifunctionality score of genes, gene function inference was performed to identify the optimal gene functions for T1DM based on the optimal ranking gene list. Considering an AUC > 0.7, six optimal gene functions for T1DM were identified, such as regulation of immune system process and receptor activity. CONCLUSIONS CEN-based gene functional inference by extending the GBA principle predicted 6 optimal gene functions for T1DM. The results may be potential paths for therapeutic or preventive treatments of T1DM.

RESUMO OBJETIVO O objetivo deste estudo é realizar uma inferência funcional genética baseada na rede de coexpressão (CEN), expandindo o escopo do princípio de "Culpa por Associação" (GBA - Guilt by Association) para prever as funções genéticas do diabetes mellitus tipo 1 (T1DM). MÉTODOS Primeiro, os dados transcritos do T1DM foram recuperados do repositório de dados genômicos para a análise dos genes diferenciais (DEGs), e foi gerada uma CEN diferencial ponderada. A área sob a curva ROC (AUC) foi escolhida para determinar a métrica de desempenho para cada termo de Ontologia Genética (GO). A análise da expressão diferencial identificou 325 DEGs no T1DM, e a análise de coexpressão gerou uma CEN diferencial com aresta de peso >0,8. RESULTADOS Um total de 282 anotações de GO com DEGs >20 foram mantidas para inferência funcional. Ao calcular a pontuação de multifuncionalidade dos genes, a inferência da função genética foi realizada para identificar as funções genéticas ideais para T1DM com base na lista de classificação genética ideal. Considerando um valor de AUC >0,7, foram identificadas seis funções genéticas ideais para a T1DM, tais como a regulação do processo imunológico e da atividade dos receptores. CONCLUSÕES A inferência funcional genética baseada em CEN, ao expandir o princípio de GBA, previu seis funções genéticas ideais para o T1DM. Os resultados podem ser caminhos potenciais para tratamentos terapêuticos ou preventivos do T1DM.

Researches on Mesenchymal Stem Cells for Treatment of Spinal Cord Injury: A Visualization Analysis / 中国康复理论与实践

Results and Conclusion A total of 236 authors were included, out of whom 49 authors published more than three papers, and high-yielding authors were mainly represented by Zeng Y S and Chen L. There were 162 countries/institutions involved, out of which 85 published more than three papers. Seventy-five journals were included, out of which Exp Neurol was the one with the most articles. There were 107 key words included, and the hot words were spinal cord injury, MSCs, transplantation, bone marrow, repair, and functional recovery, which formed six cluster groups. The trend was to extract and culture progenitor cells and induce their directional differentiation; mechanism of immune regulation, anti-inflammatory and nerve regeneration in the treatment of spinal cord injury by MSCs, as well as the research of tissue engineering technology, biological materials in this field. Objective:To analyze the research status and hotspots of mesenchymal stem cells (MSCs) for treatment of spinal cord injury in the past five years. Methods:The related literatures from 2014 to 2018 in Science Citation Index-Expanded (SCI-E) of Web of Science (WOS) were included. CiteSpace software was used to analyze the cooperation relationship of authors, countries and research institutions. The keywords were taken as nodes for co-occurrence analysis, cluster analysis, dynamic frontier evolution and burst analysis. The co-citation of journals and literatures were taken as nodes for analysis, meanwhile, the visual maps were drawn and the results were analyzed.

Research Progress on Mechanism of Yiguanjian Intervention in Liver Cirrhosis / 中国实验方剂学杂志

Liver cirrhosis caused by the repeated action of one or more causes is a pathological stage characterized by diffuse fibrosis of the liver parenchyma， formation of false lobules and regenerative nodules， portal hypertension which caused by abnormal blood vessels inside and outside the liver. The progression of cirrhosis to decompensation is characterized by severe liver damage， with ascites， gastroesophageal varices bleeding， hepatic encephalopathy and other complications， and most of the treatments are symptomatic， with high mortality and poor prognosis. At present， the traditional Chinese medicine treatment of decompensated cirrhosis can not only effectively improve liver function， but also significantly improve the 5-year survival rate of patients， which suggests that Chinese medicine has potential advantages in preventing and treating end-stage liver disease， and promoting liver cirrhosis tissue reconstruction. Modern Chinese medicine doctors believe that liver cirrhosis is mainly caused by Qi Yin deficiency （liver， spleen， kidney），internal invasion of damp-heat epidemic toxin， and collateral stasis. Deficiency of liver and kidney Yin is a common symptom of decompensated cirrhosis. Yiguanjian， one of Kidney-Nourishing and Liver-Replenishing decoction in traditional Chinese medicine ， is the representative prescription for modern clinical treatment of chronic liver disease with "deficiency of liver and kidney Yin" syndrome. Yiguanjian， created by WEI Yu-zhen （WEI Zhi-xiu）in the Qing Dynasty， Contained in "Xu Ming Yi Lei An ". Clinical studies show that Yiguanjian can effectively improve liver function in patients with liver cirrhosis， promote ascites resolution， and reduce the occurrence of hepatic encephalopathy and other related complications. Experimental research has suggested that Yiguanjian has the characteristics of multi-path， multi-level， and multi-target comprehensive regulation. The mechanism of prevention and treatment of liver cirrhosis may be mainly related to anti-oxidative stress， improving liver inflammation， improving liver cell biosynthesis， inhibiting hepatic stellate cell activation， reducing collagen deposition， improving sinusoidal vascularization and promoting liver cell regeneration. This paper reviews the progress of clinical and experimental research of Yiguanjian in the treatment of liver cirrhosis in the past 5 years， to provide some references for the clinical application and in-depth study of Yiguanjian.

Interpretation of expert consensus on diagnosis and treatment of eosinophilic granulomatous polyvasculitis in 2018 / 中国实用内科杂志

According to the different organs involved in patients, the concept of localized Eosinophilic granulomatous polyvasculitis(EGPA) was first proposed by consensus in 2018, which provides a basis for the early diagnosis and treatment of EGPA. The prognosis of patients with EGPA is related to the initial treatment. The treatment of EGPA depends on the severity of the disease, the organs involved and whether the disease is active or not. The overall treatment plan is divided into two stages: induction remission and maintenance therapy. Induced remission therapy mainly includes hormones and/or immunosuppressive agents(e.g. cyclophosphamide). After remission, azathioprine or methotrexate is recommended for maintenance therapy. In 2015, the global consensus of EGPA diagnostic and therapeutic experts recommended that the duration of treatment should be at least 24 months after remission. In combination with the latest international progress, the first Expert Consensus on Diagnosis and Treatment of EGPA in China 2018 consensus introduced the application of Bio-Targeting drugs in EGPA.