Therapeutic effect of transplantation of bone marrow mesenchymal stem cells co-cultured with bone marrow M2 macrophages on a rat model of liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSCM2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl4）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSCM2. The rats were given subcutaneous injection of CCl4 for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSCM2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl4. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSCM2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSCM2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSCM2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSCM2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl4/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.@*METHODS@#A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.@*RESULTS@#Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.@*CONCLUSION@#Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Clinical characteristics among 67 cases of botulism in Xinjiang Uygur Autonomous Region, China / 中华神经科杂志

Objective:To investigate epidemiological and clinical characteristics of botulism, and the adverse events among those received botulinum antitoxin treatment.Methods:Patients with discharge diagnosis as botulism in the Second Affiliated Hospital of Xinjiang Medical University were enrolled between 2017 and 2021. The epidemiological and clinical characteristics were evaluated. Infection and mechanical ventilation as in-hospital outcomes according to baseline characteristics were analyzed. Patients with and without the interested outcomes were compared. The adverse outcomes among those received botulinum antitoxin treatment were investigated. Those with and without the adverse outcomes were also compared.Results:Sixty-seven cases of botulism were enrolled, and most cases got sick between January and March (32/67, 47.8%); among them 62 cases were Han ethnicity (92.5%); prevalence was highest in Aksu region (15/67, 22.4%); commonly seen symptoms and signs included fatigue (58/67, 86.6%), dysphagia (48/67, 71.6%), dizziness (42/67, 62.7%), ptosis (42/67, 62.7%), blurred vision (41/67, 61.2%), and limb weakness (35/67, 52.2%). Compared with patients without in-hospital infection ( n=52), patients with in-hospital infection ( n=15) were more likely to have severe botulism (0/52 vs 5/15, χ 2=19.79, P<0.001), diplopia (16/52, 30.8% vs 11/15, χ 2=8.77, P=0.003), dysarthria (17/52, 32.7% vs 11/15, χ 2=7.91, P=0.005), consciousness disorder (1/52, 1.9% vs 4/15, χ 2=10.32, P=0.008). Compared with patients without mechanical ventilation (62/67, 92.5%), patients with mechanical ventilation (5/67, 7.5%) were more likely to have severe botulism (5/5 vs 0/62, χ 2=41.17, P<0.001), and consciousness disorder (4/5 vs 1/62, 1.6%, χ 2=29.58, P<0.001). Among 67 cases of botulism, 19 cases (28.4%) had adverse events after receiving antitoxin treatment, with an average of 6.5 days from the antitoxin treatment beginning to the adverse event onset; among the 19 cases, 18 cases (94.7%) had rash. Age, sex, and severity did not differ between the groups with ( n=19) and without adverse events ( n=48) after receiving antitoxin treatment. Conclusions:Fatigue, dysphagia, dizziness, ptosis were the most frequent symptoms and signs in the botulism in Xinjiang Uygur Autonomous Region, China. Infection was a commonly seen complication of botulism, and proactive prevention and close monitoring were needed. Adverse events after receiving antitoxin were prevalent, and might not be associated with age, sex, and severity of botulism.

Relationship between insomnia and suicidal ideation in adolescents with depressive disorder： the mediating role of rumination / 四川精神卫生

ObjectiveTo explore the mediating effect of rumination on the relationship between insomnia and suicidal ideation in adolescents with depressive disorder， so as to provide guidance for the preventions of suicidal ideation. MethodsA total of 302 adolescents with major depressive disorder in Department of Psychosomatic Medicine of Deyang People's Hospital from January to December 2020 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） clinical significance criterion for depressive disorder were enrolled. All individuals were assessed using Insomnia Severity Index （ISI）， Ruminative Response Scale （RRS） and Positive and Negative Suicide Ideation （PANSI）. Then the mediating effect of rumination in the relation between insomnia and suicidal ideation in adolescents with major depression disorder was analyzed using Process v3.2 model 4， and testified with the bias-corrected non-parametric percentile Bootstrap method. ResultsISI scores in adolescents with major depression disorder were positively correlated with PANSI score （r=0.400， P<0.01）， and were positively correlated with RRS total score， obsessive thinking and introspection factor score （r=0.378， 0.360， 0.333， P<0.01）. RRS score was also positively correlated with PANSI score （r=0.292， P<0.01）. Rumination exerted a partial mediating effect on the relationship between insomnia and suicidal ideation （β=0.174， 95% CI： 0.098~0.261）. ConclusionThe relationship between insomnia and suicidal ideation in adolescents with depressive disorder is partially mediated by rumination， additionally， insomnia can affect suicidal ideation in adolescents with depressive disorder both directly and indirectly through rumination.

Research progress on the correlation between circadian rhythm and clock genes and the pathogenesis of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is the most common microvascular complication of patients with diabetes mellitus, and it has become one of the leading causes of visual impairment among working-age people worldwide. The pathogenesis of DR is complicated with multiple mechanisms. Plenty of studies have indicated that circadian rhythm and clock genes are closely related to the pathogenesis of DR. Circadian rhythm is a physiological process regulated by clock genes, which takes 24h as a cycle and is consistent with the changes of light and dark outside. Circadian rhythm regulates various physiological activities of the body. The disturbance of circadian rhythm induces DR by affecting the blood glucose level and the physiological homeostasis of the eye in patients with diabetes mellitus, and clock genes may be involved in the pathogenesis of DR by regulating oxidative stress response, inflammatory response, retinal autophagy rhythm, mitochondrial dysfunction and endothelial progenitor cell function. This paper will introduce the generation and regulation mechanism of circadian rhythm, as well as the internal circadian rhythm of retina, and further discuss the influence of circadian rhythm and clock genes on the occurrence and development of DR, aiming to provide a reference for the prevention and treatment of DR.

New insights into effects of Kaixin Powder on depression via lipid metabolism related adiponectin signaling pathway / 中草药·英文版

OBJECTIVE@#To clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling.@*METHODS@#Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis.@*RESULTS@#Transcriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway.@*CONCLUSION@#Taken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.

Development and Application of Lower Limb Exoskeleton Rehabilitation Robot / 中山大学学报(医学科学版)

With the deepening of the aging of society， there are more and more patients with motor dysfunction of lower limb，and rehabilitation therapy for these patients is becoming more and more important. Since the 1980s， exoskeleton robots for lower-limb rehabilitation have been applied to the rehabilitation for patient with dyskinesia， especially those with dyskinesia caused by neurological diseases such as stroke. These exoskeleton robots are wearable， nonlinear and complex mechanical devices， which deserve to be studied and widely applied. In this review， the research status， clinical application and challenges of exoskeleton robots for lower-limb rehabilitation are described in three aspects according to the difference of the therapeutic sites of exoskeleton rehabilitation robots， and on the basis， the development trend of exoskeleton robots for lower-limb rehabilitation is prospected.

Research progress in the intervention of Chinese herb monomers on diabetic retinal neurodegeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)has been traditionally considered a purely microvascular disease in the retina. Currently, mainstream therapies focus only on advanced vascular complications and a single molecular target-vascular endothelial growth factor(VEGF). However, the research is shifting towards a more comprehensive view that DR is a neurovascular disease caused by neurovascular unit(NVU)injury. In the early stage of DR, diabetic retinal neurodegeneration(DRN)dominates and may precede the retinal microvascular abnormalities. Moreover, neuronal apoptosis can further lead to microvascular injury and blood-retinal barrier(BRB)disruption. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse DRN. However, no drug targeting DRN has been approved for clinical use. In recent years, it has become a trend to study the protective effect of traditional Chinese medicine on the retina. The primary research focuses on Chinese herb monomers. This article reviews the research status of representative monomers in DRN to provide references for the early treatment of DR and development of new drugs.

Preparation and polarization activity research of astragalus polysaccharide-superparamagnetic iron oxide nanocomposite / 药学学报

Size and surface modification are the two key factors affecting the effect of macrophages polarization induced by superparamagnetic iron oxide nanoparticles (SPIONs). The smaller the particle size, the better the polarization effect of SPIONs. Besides, the reasonable SPIONs surface modification method can also be used to enhance the polarization effect. In this study, SPIONs was prepared by solvothermal method and optimized by Box-Benhnken center combination design and response surface method. Furthermore, astragalus polysaccharide-superparamagnetic iron oxide nanocomplex (APS-SPIONs) was successfully constructed by EDC/NHS esterification method. The structure of APS-SPIONs was confirmed by dynamic light scatter and infrared spectrometer, and the contents of iron and polysaccharide were characterized by spectrophotometry. The effect of APS-SPIONs on inducing mouse macrophages RAW264.7 polarization was investigated by flow cytometry. The RAW264.7 macrophages-HepG2 human hepatoma cancer cells Transwell co-culture system was established to investigate APS-SPIONs improve anti-tumor function of macrophages in vitro, and the proliferation activity of APS-SPIONs on RAW264.7 detected by cell counting kit-8 (CCK-8) method. The results showed that the average particle size and zeta potential of APS-SPIONs were (82.93 ± 1.47) nm and (-24.00 ± 0.47) mV. Polysaccharide and Fe content were 8.69% and 7.04%, respectively. APS-SPIONs effectively induced the polarization of RAW264.7 into M1 type in vitro, improving the anti-tumor ability of macrophages in a co-culture system, without effecting the proliferation of macrophages. Our study provides a drug development strategy and preliminary research results to educate macrophages and reshape the tumor immune microenvironment to achieve tumor-killing effects.

A consensus on the management of allergy in kindergartens and primary schools / 中国学校卫生

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Effect of Elevated Basal LH on IVF-ET Outcomes in Patients with Polycystic Ovary Syndrome / 中山大学学报(医学科学版)

ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.

Clinical Effect of Tiaoxin Formula in Treatment of Patients with Coronary Heart Disease and Anxiety/Depression and Its Impact on Serum 5-HT， β-TG and MPO Levels / 中国实验方剂学杂志

ObjectiveTo explore the clinical effect of Tiaoxin formula in the treatment of patients with coronary heart disease and anxiety/depression and its impact on serum levels of 5-hydroxytryptamine （5-HT）， β- thromboglobulin （β-TG） and myeloperoxidase （MPO）. MethodA total of 66 patients with coronary heart disease and anxiety/depression were randomly divided into the Tiaoxin formula group and Deanxit group， 33 cases in each group. Both groups were given fundamental western treatment for coronary heart disease. Additionally， the Deanxit group was treated with flupentixol and melitracen tablets and the Tiaoxin formula group was treated with Tiaoxin Formula. The treatment lasted 8 weeks. Before and after treatment， the changes of clinical efficacy， Patient Health Questionnaire （PHQ-9）， Generalized Anxiety Disorder （GAD-7） scale， Seattle Angina Questionnaire （SAQ）， heart rate variability， and serum 5-HT， β-TG and MPO levels， and incidence of adverse reactions in the two groups were observed. ResultThere was no significant difference in the baseline indexes of patients in the two groups， and thus the two groups were comparable. After treatment for 8 weeks， the total effective rate for traditional Chinese medicine （TCM） syndromes in the Tiaoxin Formula group was 87.88% （29/33） higher than 63.64% （21/33） in the Deanxit group （Z=-2.653， P<0.05）. Compared with those before treatment， the PHQ-9 and GAD-7 scores of the two groups were decreased at week 4 and 8 of treatment （P<0.05）， and there was no statistical difference between two groups. And the SAQ dimension scores of the two groups were increased at week 4 and 8 of treatment （P<0.05）. Compared with the Deanxit group， the Tiaoxin Formula group had elevation in two dimension scores： Physical limitation and angina stability （P<0.05）. Compared with the conditions before treatment， the serum 5-HT level in the two groups were increased， while the β-TG and MPO levels were lowered （P<0.05）， and there was no distinct difference between two groups. In addition， the standard deviation of normal-to-normal intervals （SDNN） and standard deviation of average normal-to-normal intervals （SDANN） of the heart rate variability in the Tiaoxin formula group were elevated after treatment （P<0.05）， which were more significant than those of the Deanxit group （P<0.05）. During the treatment period， the incidence of adverse drug reactions in the Tiaoxin formula group was lower than that in the Deanxit group （P<0.05）， and no adverse events were observed in the two groups. ConclusionTiaoxin formula was effective for the treatment of patients with coronary heart disease accompanied by anxiety and depression， which improved the clinical symptoms， increased serum 5-HT levels， and decreased serum β-TG and MPO levels， and had few adverse reactions and high safety for patients， showing a high clinical value.

Effectiveness and Safety of Chinese Medicine at Shenque (CV 8) for Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD.@*OBJECTIVE@#To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM).@*METHODS@#China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool.@*RESULTS@#Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I2=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I2=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I2=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall.@*CONCLUSIONS@#Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).

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.

Expression and significance of jumonji domain-containing protein 2B and hypoxia inducible factor-1α in non-Hodgkin lymphoma tissues in children / 中国当代儿科杂志

OBJECTIVES@#To investigate the expression and significance of jumonji domain-containing protein 2B (JMJD2B) and hypoxia-inducible factor-1α (HIF-1α) in non-Hodgkin's lymphoma (NHL) tissues in children.@*METHODS@#Immunohistochemistry was used to detect the expression of JMJD2B and HIF-1α in lymph node tissue specimens from 46 children with NHL (observation group) and 24 children with reactive hyperplasia (control group). The relationship between JMJD2B and HIF-1α expression with clinicopathological characteristics and prognosis in children with NHL, as well as the correlation between JMJD2B and HIF-1α expression in NHL tissues, were analyzed.@*RESULTS@#The positive expression rates of JMJD2B (87% vs 21%) and HIF-1α (83% vs 42%) in the observation group were higher than those in the control group (P<0.05). The expression of JMJD2B and HIF-1α was correlated with serum lactate dehydrogenase levels and the risk of international prognostic index in children with NHL (P<0.05). The expression of JMJD2B was positively correlated with the HIF-1α expression in children with NHL (rs=0.333, P=0.024).@*CONCLUSIONS@#JMJD2B and HIF-1α are upregulated in children with NHL, and they may play a synergistic role in the development of pediatric NHL. JMJD2B can serve as a novel indicator for auxiliary diagnosis, evaluation of the severity, treatment guidance, and prognosis assessment in pediatric NHL.

Activation of intestinal mucosal TLR4/NF-κB pathway is associated with renal damage in mice with pseudo-sterile IgA nephropathy / 细胞与分子免疫学杂志

Objective To investigate the effect of intestinal mucosal Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathway on renal damage in pseudo-sterile IgA nephropathy (IgAN) mice. Methods C57BL/6 mice were randomly divided into experimental group (pseudosterile mouse model group), control group (IgAN mouse model group), pseudosterile mouse blank group, and normal mouse blank group. Pseudosterile mice were established by intragastric administration of quadruple antibiotics once a day for 14 days. The pseudosterile IgAN mouse model was set up by combination of oral bovine serum albumin (BSA) administration and staphylococcal enterotoxin B (SEB) injection. The pathological changes of renal tissue were observed by immunofluorescence staining and PAS staining, and the intestinal mucosa barrier damage indicators lipopolysaccharide(LPS), soluble intercellular adhesion molecule 1(sICAM-1) and D-lactate(D-LAC) were analyzed by ELISA. Biochemical analysis was used to test 24 hour urine protein, serum creatinine and blood urea nitrogen. The mRNA and protein levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB (NF-κB) were detected by reverse transcription PCR and Western blot analysis. Results The kidney damage of pseudosterile IgAN mice was more severe than that of IgAN mice, and the expressions of intestinal mucosal barrier damage markers (LPS, sICAM-1 and D-LAC) were significantly increased in pseudosterile IgAN mice. In addition, the expressions of TLR4, MyD88, and NF-κB level were all up-regulated in the intestinal tissues of IgAN pseudosterile mice. Conclusion Intestinal flora disturbance leads to intestinal mucosal barrier damage and induces activation of TLR4 signaling pathway to mediate renal injury in IgAN.

Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition / 中国中药杂志

To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. The experimental results showed that VFD and DS basically kept the original color of MFOEU. The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. Considering the color of MFOEU, the suitable drying methods were DS and VFD. Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas.

Assay of amino acids in leaves of Eucommia ulmoides under arbor forest mode and leaf-oriented cultivation mode by pre-column derivatization HPLC / 中国中药杂志

This study aims to develop the pre-column derivatization high performance liquid chromatography(HPLC) method for the determination of 16 kinds of amino acids in Eucommia ulmoides leaves, and compare the content of amino acids in the leaves harvested at different time and under leaf-oriented cultivation mode(LCM) and arbor forest mode(AFM). The HPLC conditions are as below: phenyl isothiocyanate(PITC) as pre-column derivatization agent, Agilent ZORBAX C_(18 )column(4.6 mm×250 mm, 5 μm), mobile phase A of acetonitrile-water(80∶20), mobile phase B of 0.1 mol·L~(-1) sodium acetate solution-acetonitrile(94∶6), gradient elution, flow rate of 1.0 mL·min~(-1), injection volume of 5 μL, column temperature of 40 ℃, and detection wavelength of 254 nm. The HPLC profile indicated well separation of 16 kinds of amino acids and the amino acid content in E. ulmoides leaves was up to 16.26%. In addition, the amino acid content in leaves of E. ulmoides under LCM was higher than under AFM. The amino acid content varied with the harvesting time. Through orthogonal partial least squares discriminant analysis, the amino acids of E. ulmoides under LCM and AFM were compared, which can distinguish the leaves under LCM from those under AFM. Principal component analysis was applied to comprehensively score the amino acids of E. ulmoides leaves. The results showed that the score of leaves under LCM was higher than that under AFM. Nutritional evaluation results indicated that the proteins in E. ulmoides leaves belonged to high-quality vegetable proteins. The established method for the determination of amino acid content is reliable. With the amino acid content as index, the leaf quality of E. ulmoides under LCM is better than that under AFM. This study lays a theoretical basis for the promotion of LCM for E. ulmoides and the development of medicinal and edible products from E. ulmoides leaves.

Efficacy and safety of new oral anticoagulants in patients with nonvalvular atrial fibrillation after left atrial appendage occlusion：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of new oral anticoagulants （NOACs） in patients with nonvalvular atrial fibrillation after left atrial appendage occlusion （LAAO）. METHODS Retrieved from PubMed， Embase， Web of Science， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） and cohort studies about NOACs （trial group） versus warfarin or dual antiplatelet agents （control group） were collected during the inception and November 2022. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 10 studies were included， involving 2 RCTs and 8 cohort studies， with a total of 2 653 patients. RCT results showed that there was no statistically significant difference in the incidence of device-related thrombosis （DRT）， stroke/ systemic embolism （SSE）， major bleeding events， total bleeding events or all-cause mortality between 2 groups （P＞0.05）. Results of cohort studies showed that compared with dual antiplatelet agents， there was no statistically significant difference in the incidence of DRT， stroke/SSE， major bleeding events or all-cause mortality in the trial group （P＞0.05）. Compared with warfarin， the incidence of DRT [RR＝0.40， 95%CI　（0.19，0.82）， P＝0.01] and total bleeding events [RR＝0.28， 95%CI　（0.18， 0.44）， P＜ 0.000 01] in the trial group were decreased significantly； there was no statistical significance in the incidence of stroke/SSE， major bleeding events or all-cause mortality （P＞0.05）. CONCLUSIONS For patients with nonvalvular atrial fibrillation after LAAO， NOACs have comparable antithrombotic efficacy and safety with dual antiplatelet agents， and the incidence of DRT and total bleeding events are lower than warfarin.

Preparation of two tanshinone Ⅱ_A-astragaloside Ⅳ co-loaded nano-delivery systems and in vitro antitumor activity comparison / 中国中药杂志

This study screened excellent carriers for co-loading tanshinone Ⅱ_A(TSA) and astragaloside Ⅳ(As) to construct antitumor nano-drug delivery systems for TSA and As. TSA-As microemulsions(TSA-As-MEs) were prepared by water titration. TSA-As metal-organic framework(MOF) nano-delivery system was prepared by loading TSA and As in MOF by the hydrothermal method. Dynamic light scattering(DLS), transmission electron microscopy(TEM), and scanning electron microscopy(SEM) were used to characterize the physicochemical properties of the two preparations. Drug loading was determined by HPLC and the effects of the two preparations on the proliferation of vascular endothelial cells, T lymphocytes, and hepatocellular carcinoma cells were detected by the CCK-8 method. The results showed that the particle size, Zeta potential, and drug loading of TSA-As-MEs were(47.69±0.71) nm,(-14.70±0.49) mV, and(0.22±0.01)%, while those of TSA-As-MOF were(258.3±25.2) nm,(-42.30 ± 1.27) mV, and 15.35%±0.01%. TSA-As-MOF was superior to TSA-As-MEs in drug loading, which could inhibit the proliferation of bEnd.3 cells at a lower concentration and improve the proliferation ability of CTLL-2 cells significantly. Therefore, MOF was preferred as an excellent carrier for TSA and As co-loading.