Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway / 中国中药杂志

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.

Correlation between contrast-enhanced ultrasound parameters and Crohn's disease activity / 中华内科杂志

Objective: By investigating the correlation between quantitative parameters of contrast enhanced ultrasound (CEUS) and commonly used activity assessment indicators of Crohn's disease (CD), and comparing the predictive power of laboratory inflammatory indicators with CEUS on Crohn's disease (CD), the significance of CEUS was evaluated. Methods: A case-control study. From October 2019 to December 2021, the clinical data of 67 patients with CD who were diagnosed by endoscopy and underwent contrast-enhanced ultrasonography were retrospectively analyzed in the First Affiliated Hospital with Nanjing Medical University, and their routine ultrasound and CEUS parameters, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) and simplified endoscopic score for Crohn's disease (SES-CD) were collected. Using SES-CD as the standard, the patients were divided into a remission group and an active group, and the correlation of laboratory inflammatory indexes and contrast-enhanced ultrasound parameters with CDAI and SES-CD were evaluated. Besides, the ROC curve was used to analyze the predictive efficacy of each index on CD endoscopic activity. Results: A total of 67 patients were included in this study. According to the SES-CD score, there were 17 patients in the remission group and 50 patients in the active group. Except for the coefficient of the enhancement wash in slope and time to peak (TTP), the peak intensity (PI), area under the angiography curve, and laboratory inflammatory indexes were significantly different between the two groups (P<0.05), which also showed a moderate positive correlation with CDAI and SES-CD (P<0.05). ROC analysis showed that among the non-invasive indicators, PI and area under the angiography curve had the highest AUCs for predicting CD endoscopic activity, which were 0.912 and 0.891, respectively; with SES-CD taking >3 as the cut-off value, the corresponding sensitivities were 78.0% and 72.0%, with specificities of 100.0% and 94.1%, respectively. Conclusion: CEUS can objectively and repeatedly evaluate the disease activity of CD patients, and has great clinical application value, which can be used as a reliable imaging method for diagnosis and follow-up of patients with Crohn's disease.

Efficacy of intramuscular injection of Xiyanping injection for the treatment of acute bronchitis in children: a multicenter, randomized, parallel-controlled clinical study / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of Xiyanping injection through intramuscular injection for the treatment of acute bronchitis in children.@*METHODS@#A prospective study was conducted from December 2021 to October 2022, including 78 children with acute bronchitis from three hospitals using a multicenter, randomized, parallel-controlled design. The participants were divided into a test group (conventional treatment plus Xiyanping injection; n=36) and a control group (conventional treatment alone; n=37) in a 1:1 ratio. Xiyanping injection was administered at a dose of 0.3 mL/(kg·d) (total daily dose ≤8 mL), twice daily via intramuscular injection, with a treatment duration of ≤4 days and a follow-up period of 7 days. The treatment efficacy and safety were compared between the two groups.@*RESULTS@#The total effective rate on the 3rd day after treatment in the test group was significantly higher than that in the control group (P<0.05), while there was no significant difference in the total effective rate on the 5th day between the two groups (P>0.05). The rates of fever relief, cough relief, and lung rale relief in the test group on the 3rd day after treatment were higher than those in the control group (P<0.05). The cough relief rate on the 5th day after treatment in the test group was higher than that in the control group (P<0.05), while there was no significant difference in the fever relief rate and lung rale relief rate between the two groups (P>0.05). The cough relief time, daily cough relief time, and nocturnal cough relief time in the test group were significantly shorter than those in the control group (P<0.05), while there were no significant differences in the fever duration and lung rale relief time between the two groups (P>0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05).@*CONCLUSIONS@#The overall efficacy of combined routine treatment with intramuscular injection of Xiyanping injection in the treatment of acute bronchitis in children is superior to that of routine treatment alone, without an increase in the incidence of adverse reactions.

EPCs-exos combined with tanshinone Ⅱ_A protect vascular endothelium cells from oxidative damage via PI3K/Akt pathway / 中国中药杂志

This study aims to investigate the molecular mechanism of tanshinone Ⅱ_(A )(TaⅡ_A) combined with endothelial progenitor cells-derived exosomes(EPCs-exos) in protecting the aortic vascular endothelial cells(AVECs) from oxidative damage via the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt) pathway. The AVECs induced by 1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine(POVPC) were randomly divided into model, TaⅡ_A, EPCs-exos, and TaⅡ_A+EPCs-exos groups, and the normal cells were taken as the control group. The cell counting kit-8(CCK-8) was used to examine the cell proliferation. The lactate dehydrogenase(LDH) cytotoxicity assay kit, Matrigel assay, DCFH-DA fluorescent probe, and laser confocal microscopy were employed to examine the LDH release, tube-forming ability, cellular reactive oxygen species(ROS) level, and endothelial cell skeleton morphology, respectively. The enzyme-linked immunosorbent assay was employed to measure the expression of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of PI3K and Akt. Compared with the control group, the model group showed decreased cell proliferation and tube-forming ability, increased LDH release, elevated ROS level, obvious cytoskeletal disruption, increased expression of IL-1β, IL-6, and TNF-α, and down-regulated mRNA and protein levels of PI3K and Akt. Compared with the model group, TaⅡ_A or EPCs-exos alone increased the cell proliferation and tube-forming ability, reduced LDH release, lowered the ROS level, repaired the damaged skeleton, decreased the expression of IL-1β, IL-6, and TNF-α, and up-regulated the mRNA and protein levels of PI3K and Akt. TaⅡ_A+EPCs-exos outperformed TaⅡ_A or EPCs-exos alone in regulating the above indexes. The results demonstrated that TaⅡ_A and EPCs-exos exerted a protective effect on POVPC-induced AVECs by activating the PI3K/Akt pathway, and the combination of the two had stronger therapeutic effect.

Transcriptional regulation mechanism of differential accumulation of flavonoids in leaves and roots of Sarcandra glabra based on metabonomics and transcriptomics / 中国中药杂志

This study aims to explore the molecular regulation mechanism of the differential accumulation of flavonoids in the leaves and roots of Sarcandra glabra. Liquid chromatography-mass spectrometry(LC-MS) and high-throughput transcriptome sequencing(RNA-seq) were employed to screen out the flavonoid-related differential metabolites and differentially expressed genes(DEGs) encoding key metabolic enzymes. Eight DEGs were randomly selected for qRT-PCR verification. The results showed that a total of 37 flavonoid-related differential metabolites between the leaves and roots of S. glabra were obtained, including pinocembrin, phlorizin, na-ringenin, kaempferol, leucocyanidin, and 5-O-caffeoylshikimic acid. The transcriptome analysis predicted 36 DEGs associated with flavonoids in the leaves and roots of S. glabra, including 2 genes in the PAL pathway, 3 genes in the 4CL pathway, 2 genes in the CHS pathway, 4 genes in the CHI pathway, 2 genes in the FLS pathway, 1 gene in the DFR pathway, 1 gene in the CYP73A pathway, 1 gene in the CYP75B1 pathway, 3 genes in the PGT1 pathway, 6 genes in the HCT pathway, 2 genes in the C3'H pathway, 1 gene in the CCOAOMT pathway, 1 gene in the ANR pathway, 1 gene in the LAR pathway, 2 genes in the 3AT pathway, 1 gene in the BZ1 pathway, 2 genes in the IFTM7 pathway, and 1 gene in the CYP81E9 pathway. Six transcription factors, including C2H2, bHLH, and bZIP, were involved in regulating the differential accumulation of flavonoids in the leaves and roots of S. glabra. The qRT-PCR results showed that the up-or down-regulated expression of the 8 randomly selected enzyme genes involved in flavonoid synthesis in the leaves and roots of S. glabra was consistent with the transcriptome sequencing results. This study preliminarily analyzed the transcriptional regulation mechanism of differential accumulation of flavonoids in the leaves and roots of S. glabra, laying a foundation for further elucidating the regulatory effects of key enzyme genes and corresponding transcription factors on the accumulation of flavonoids in S. glabra.

The protective effect of terpinen-4-ol on inflammatory injury of VSMCs induced by high glucose through improving autophagic flux disorder / 中国药理学通报

Aim To investigate the effect of terpinen-4-ol (T40) on inflammatory injury of vascular smooth muscle cells (VSMCs) induced by high glucose based on the improvement of autophagic flow disorder and involved molecular signals. Methods The scratch test was used to analyze the migration ability of VSMCs, the levels of IL-1β and IL-6 in cell culture supernatant were measured by ELISA, the expression levels of inflammation-related proteins NF-κb p65, p-NF-κb p65, IL-1β, IL-18 and autophagy-related proteins p62, LC3-HYLC3-I, Beclinl, p-Beclinl were de-tected by Western blot. Results T40 inhibited migration of VSMCs induced by high glucose, reduced the secretion and release of pro-inflammatory factors IL-1β and IL-6, inhibited the expression of p-NF-κb p65/ NF-κb p65, IL-1β, IL-18, downregulated the expression of p62, LC3-TJ/LC3- I and p-Beclinl at same time. After interfering the autophagic flux of VSMCs with autophagy inhibitor chloroquine (CQ) , T40 pre-treatment significantly inhibited the protein expression levels of the above inflammatory factors and autophagy-related signals which mediated by CQ. Conclusion T40 inhibits the inflammatory injury of VSMCs induced by high glucose through improving the autophagic flow disorder.

Progress in imaging and functional assessment of myopic fundus tessellation changes / 国际眼科杂志(Guoji Yanke Zazhi)

Myopia has become a serious global burden of visual impairment and blindness, and the World Health Organization has included the prevention and treatment of myopia in its global blindness prevention program. Many ocular pathological alterations that follow from advanced myopia could cause visual impairment and even blindness in severe situations. Myopia is becoming more prevalent and has a greater impact on young people. Myopia's social repercussions are becoming more widely known. One of the several fundus alterations linked to myopia is tessellated fundus, which is the earliest lesion in the natural course of myopic fundus lesions and an important clinical marker for the development of retinopathy. Currently, there are several different methods of grading fundus tessellation, all of which are graded subjectively by fundus color photography. One can investigate the morphological characteristics and functional status of the tessellated fundus with ophthalmoscope, fundus photography, optical coherence tomography, electroretinogram, microperimetry and other modal images. In this study, the imaging properties and common applications of the tessellated fundus are reviewed to provide appropriate resources for clinical ophthalmology.

Mechanism of Tongmai Yangxin pill to reduce the no-reflow after myocardial ischemia and reperfusion by activating HIF-1α/eNOS signaling pathway up-regulated by GPER / 药学学报

The Tongmai Yangxin pill (TMYX) has potential clinical effects on no-reflow (NR); however, the effective substances and mechanisms by which this occurs remain unclear. This study evaluates the cardioprotective effects and molecular mechanisms of TMYX against NR. We used a myocardial NR rat model (2 h after myocardial ischemia and 2 h after reperfusion) to confirm the effect and mechanism of action of TMYX in alleviating NR. In vitro studies in isolated coronary microvasculature of NR rats and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of TMYX and determine the main components, targets, and pathways of TMYX, respectively. The experiment was approved by the Ethics Committee of Hunan University of Chinese Medicine (LLBH-202212160001). TMYX showed therapeutic effects on NR by improving cardiac structure and function, reducing NR, ischemic areas, and cardiomyocyte injury, and decreasing the content of cardiac troponin I (cTnI). Moreover, the mechanism of TMYX predicted by network pharmacology is related to the hypoxia inducible factor-1 (HIF-1), nuclear factor kappa-B (NF-κB), and tumor necrosis factor (TNF) signaling pathways. TMYX increased the expression of G protein-coupled estrogen receptor (GPER), phospho-extracellular signal-regulated kinase (p-ERK), and HIF-1α. In vitro, TMYX enhanced the diastolic function of coronary microvascular cells; however, this effect was inhibited by GPER inhibitor (G-15), eNOS inhibitor (L-NAME), and sGC inhibitor (ODQ). This study integrates pharmacology and experimental evaluation to reveal that TMYX activates HIF-1α/eNOS signaling pathway by upregulating GPER to relax coronary microvessels, thereby significantly alleviating NR.

Terpine-4-ol on inhibiting vascular smooth muscle cell calcification by improving mitochondrial dynamics / 药学学报

The aim of this study was to investigate the role and mechanism of terpinen-4-ol (T4O) on high glucose (HG) -induced calcification in vascular smooth muscle cell (VSMC). To investigate the role of T4O on HG-induced calcium deposition, osteogenic phenotypic transformation and mitochondrial dynamics in VSMC, Mdivi-1, a mitochondrial dynamin-related protein 1 (Drp-1) inhibitor, was used to analyze the correlation between mitochondrial dynamics and VSMC calcification and the role of T4O. Alizarin red S staining was used to observe calcium salt deposition and flow cytometry to detect intracellular Ca2+ content; Western blot and immunofluorescence were used to detect the expression of phenotypic switching-related markers α-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2) and Runt related transcription factor 2 (Runx2), and mitochondrial dynamics-related markers mitofusin 1 (MFN1), mitofusin 2 (MFN2) and Drp-1. The results showed that low and high doses of T4O could inhibit HG-induced down-regulation of α-SMA, MFN1 and MFN2 expression levels, and up-regulation of BMP2, Runx2 and Drp-1 expression levels, reduce intracellular Ca2+ content and calcium salt deposition, and effectively inhibit HG-induced VSMC calcification and mitochondrial dynamics disorders. The T4O group, Mdivi-1 group and T4O+Mdivi-1 group were able to up-regulate the expression levels of HG-induced α-SMA, MFN1 and MFN2, down-regulate the protein expression levels of BMP2, Runx2 and Drp-1, and inhibit calcium salt deposition, and there was no significant difference between the above indexes in the T4O and T4O+Mdivi-1 groups. The above findings suggest that T4O can inhibit the expression level of Drp-1, regulate the disturbance of mitochondrial dynamics, and suppress HG-induced VSMC calcification.

Studies on newly recognized chronic sialadenitis / 北京大学学报(医学版)

Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by 131I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland, elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues, allergic history, increased expression of allergy-related cytokines, such as IL-4, IL-5, IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.

Quantitative Pulmonary Administration of Essential Oil from Alpiniae Zerumbet Fructus for Treatment of Emphysema / 中国实验方剂学杂志

ObjectiveTo investigate the effect of quantitative pulmonary administration of the essential oil from Alpiniae Zerumbet Fructus （EOAZF） on porcine pancreatic elastase （PPE）-induced emphysema in mice and explore its action mechanism. MethodC57BL/6J mice were randomly divided into five group， namely the control group， model group， low- （2 mg·kg-1） and high-dose （20 mg·kg-1） EOFAZ groups， and positive control dexamethasone （DEX，1 mg·kg-1） group. The mice were treated with pulmonary administration of PPE using a microsprayer aerosolizer， once every seven days， for four times in total， for inducing emphysema. During this period， EOFAZ were administered with a quantitative microsprayer aerosolizer once every other day， for 14 times. The lung tissues were then sampled and stained with hematoxylin-eosin （HE） for observing the morphological changes and calculating the pulmonary mean linear intercept （MLI）. The concentrations of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the plasma were determined by enzyme-linked immunosorbent assay （ELISA）. The activities of superoxide dismutase （SOD） and catalase （CAT） and the content of malondialdehyde （MDA） in the lung tissues were measured using the biochemical assay kits. The protein expression levels of nuclear factor E2-related factor 2 （Nrf2）， quinone oxidoreductase1 （NQO1）， B cell lymphoma-2 （Bcl-2）-associated X protein （Bax）， and Bcl-2 in lung tissues were detected by Western blot. ResultThe results of lung morphological observation and MLI detection showed that compared with the control group， the model group showed obvious inflammatory infiltration， alveolar enlargement and fusion， and increased MLI （P<0.05）. Compared with the model group， EOFAZ effectively alleviated the pathological changes such as alveolar dilatation， pulmonary inflammatory cell infiltration， and lung cell apoptosis caused by PPE， and decreased the MLI （P<0.05）. As revealed by ELISA， the inflammatory level of mice in the model group increased significantly （P<0.01）， while the TNF-α， IL-1β， and IL-6 levels in the plasma were decreased after quantitative administration of EOFAZ （P<0.01）. Compared with the control group， the model group exhibited significantly enhanced oxidative stress （P<0.01）. After treatment with EOFAZ by quantitative administration， the activities of SOD and CAT in the lung tissue were increased （P<0.01） and the content of MDA was decreased （P<0.01）. Western blot results demonstrated that the apoptosis-related protein expression in the model group was increased significantly as compared with that in the control group （P<0.01）， whereas the expression levels of antioxidant stress proteins Nrf2 and NQO1 declined （P<0.05）. The relative protein expression of apoptosis-related proteins Bax/Bcl-2 in the EOFAZ groups was lower than that in the model group （P<0.01）， while the expression of antioxidant stress proteins Nrf2 and NQO1 was higher （P<0.05）. ConclusionQuantitative pulmonary administration of EOFAZ effectively alleviates the inflammation and oxidative stress， reduces lung cell apoptosis， and hinders the occurrence and development of emphysema. Its antioxidant mechanism is closely related to the up-regulation of Nrf2 and its downstream NQO1.

Neuroprotective Effect and Mechanisms of Notoginsenosides：A Review / 中国实验方剂学杂志

Notoginsenosides， the saponins extracted from Panax notoginseng， have many pharmacological effects， such as anti-inflammation， anti-oxidation， anti-tumor， nervous system and cardiovascular system protection， microcirculation improvement and calcium overload inhibition. At present， notoginsenosides are widely used clinically for treating many diseases with good efficacy， especially for nervous system diseases such as stroke， stroke sequelae and Alzheimer's disease. In recent years， the mechanism underlying their neuroprotective effect has been continuously explored. To advance the applied research on notoginsenosides in the prevention and treatment of central nervous system diseases， this paper， combined with the latest reports， summarizes their neuroprotective effect and mechanisms in terms of regulating voltage-gated ion channels， protecting nerve cells and neurovascular unit， inhibiting oxidative stress and inflammatory reaction， promoting angiogenesis and reducing excitatory neurotoxicity. Although the protective mechanism of notoginsenosides for the nervous system mainly involves the above several aspects， some of them still remain to be fully elucidated， which necessitates the further exploration of neuroprotective effect of notoginsenosides with molecular biology， metabolomics， proteomics and other technologies.

Essential Oil from Alpiniae Zerumbet Fructus Alleviates High Glucose-induced HUVEC Injury via TXNIP Signaling Pathway / 中国实验方剂学杂志

Objective:To study the protective effect of essential oil from Alpiniae Zerumbet Fructus （EOAZF） against high glucose （HG）-induced injury of human umbilical vein endothelial cells （HUVECs） <italic>in vitro</italic>， so as to provide experimental evidence for the treatment of diabetes-induced cardiovascular diseases with EOAZF. Method:The cells were divided into the normal group， model group （25 mmol·L^-1 glucose）， positive control group （100 mg·L^-1 vitamin C）， and the low- （0.25 μg·L^-1）， medium- （1 μg·L^-1）， and high-dose （4 μg·L^-1） EOAZF groups. The HUVECs were damaged by HG. The secretion amounts of malondialdehyde （MDA）， nitric oxide （NO）， and endothelin-1 （ET-1） in HUVECs of different groups were measured to assess the protective effect of EOAZF against HG-induced injury. The effects of EOAZF on the apoptosis and reactive oxygen species （ROS） generation of HUVECs damaged by HG were detected by Annexin V-fluorescein isothiocyanate/propidium iodide （Annexin V-FITC/PI） staining and dichloro-dihydro-fluorescein diacetate （DCFH-DA） assay. The protein and mRNA expression levels of thioredoxin interacting protein （TXNIP） and thioredoxin 1 （Trx-1） were determined by Western blot and Real-time polymerase chain reaction （Real-time PCR）， followed by the measurement of total intracellular Trx-1 activity with insulin disulfide reduction method. Result:The comparison with the control group revealed that the proliferation of HUVECs in the model group was significantly inhibited and their shape was damaged. Compared with the model group， EOAZF protected HUVECs against HG-induced injury in a concentration-dependent manner. The secretion amounts of MDA and ET-1 （<italic>P</italic><0.05） in the model group were increased in contrast to those in the control group， while the NO level was decreased （<italic>P</italic><0.01）. Compared with the model group， EOAZF at all the three concentrations， especially at 4 μg·L^-1， obviously reduced the secretion of MDA and ET-1 （<italic>P</italic><0.05）， but elevated NO after HG induction （<italic>P</italic><0.05）. The cell apoptosis assay and ROS detection results demonstrated that the apoptosis and ROS level in the model group were higher than those in the control group （<italic>P</italic><0.01）. Compared with the model group， EOAZF at 4 μg·L^-1significantly lowered the ROS level and apoptosis （<italic>P</italic><0.05） of HUVECs damaged by HG. The Western blot assay and Trx-1 activity detection uncovered that the protein and mRNA expression levels of TXNIP in the model group were significantly up-regulated as compared with those in the control group （<italic>P</italic><0.05）， whereas the Trx-1 activity was decreased （<italic>P</italic><0.01）. Compared with the model group， EOAZF at 4 μg·L^-1significantly down-regulated the mRNA and protein （<italic>P</italic><0.05） expression levels of TXNIP and enhanced the total Trx-1 activity （<italic>P</italic><0.05） in HUVECs， thus suppressing the oxidative stress. Conclusion:EOAZF exerts the protective effects against HG-induced injury in HUVECs by improving the endothelial function and reducing intracellular ROS and apoptosis. Its efficacy in anti-oxidative stress may be related to the down-regulation of mRNA and protein expression levels of TXNIP and the enhancement of Trx-1 activity.

Salidroside inhibits endothelial-mesenchymal transition by regulating KLF4/eNOS signaling pathway / 中国药理学通报

Aim To investigate the effect and mechanism of salidroside (SAL) on homocysteine (Hcy)-induced endothelial-mesenchymal transition (EndMT) based on the KLF4/eNOS signaling pathway. Methods (1) Salidroside inhibited Hcy-induced EndMT. HUVECs were pretreated with different concentrations of SAL for 2 h, then followed by Hcy (1 mmol · L-l) co-incubation for 48 hours to induce EndMT. The expression levels of VE-cadherin, α-SMA, KLF4 and eNOS were detected by Western blot, scratch repair experiment was used to determin cell migration ability, the level of NO in cells was determined by nitrate reductase method, and the expression and location of KLF4 were observed by immunofluorescence technology. (2) The signal mechanism of SAL inhibiting End-MT through KLF4/eNOS signal was studied. siRNA mediated knockdown of KLF4 in HUVECs, and the protein expression levels of VE-cadherin, α-SMA, KLF4 and eNOS in each group were determined by Western blot. Results Western blotting demonstrated that SAL significantly reversed the Hcy-induced increase in α-SMA and KLF4 expression and decrease in VE-cadherin and eNOS expression. The immunofluorescence analysis suggested that SAL inhibited the translocation of KLF4 from cytoplasm to nucleus. (2) Silencing KLF4 down-regulated the expression of α-SMA and KLF4, and up-regulated the expression of VE-cadherin and eNOS. Compared with the group of SAL + siKLF4, there was no significant difference in the effect of SAL group and siKLF4 group on phenotypic markers. Conclusions Salidroside inhibits EndMT induced by Hcy, which may be related to the regulation of KLF4/eNOS signaling pathway.

Liver Tissue-specific Genes IGFALS,CYP3A4,SLC22A1 and CYP2E1 May be Associated with Poor Prognosis of Liver Cancer / 中国医学科学院学报

Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With

Inflammation grading and sialoendoscopic treatment of 131I radioiodine-induced sialadenitis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the inflammation grading of 131I radioiodine-induced sialadenitis based upon sialoendoscopic and sialographic appearances, and to evaluate the results of sialoendoscopic intervention.@*METHODS@#The patients diagnosed with 131I radioiodine-induced sialadenitis and underwent sialoendoscopic exploration and intervention procedures in Peking University Hospital of Stomatology from Nov. 2012 to Oct. 2018 were included in this study. The appearances of sialogaphy and sialoendoscopy were analyzed and classified. The treatment options included irrigation with saline and dexamethasone and mechanical dilatation by sialoendoscope. The patients were followed up after treatment.@*RESULTS@#Forty-two patients with 131I radioiodine-induced sialadenitis were included. There were 5 males and 37 females, with a male-to-female ratio of 1 ∶7.4. Symptoms included recurrent swelling and pain in the parotid glands, and dry mouth. Sialography showed stenosis in the main duct,and in some cases nonvisua-lization of the branches. Sialoendoscopy showed narrowing of the main duct, and the branch duct atresia was seen. The appearances of sialogaphy and sialoendoscopy were analyzed and classified into 3 groups: (1) Mild inflammation: stenosis and ectasia occurred in the main duct, whereas the 0.9 mm sialoendoscope could pass through easily. (2) Moderate inflammation: one point of severe stricture could be seen in the main duct where 0.9 mm sialoendoscope could not be passed through. (3) Severe inflammation: two points or more of severe strictures or diffused strictures occurred in the main duct. Thirty-three patients with 65 affected glands were examined by both sialography and sialoendoscopy. Eight glands were classified as mild inflammation, 23 glands moderate inflammation, and 34 glands severe inflammation. The duration of follow-up ranged from 3-72 months. The clinical results were evaluated as good in 22 glands, fair in 22 glands, and poor in 19 glands, with an overall effective rate of 69.8% (44/63).@*CONCLUSION@#The clinical, sialographic and sialoendoscopic appearances of 131I radioiodine-induced sialadenitis showed their characteristics. We proposed an inflammation grading standard for the 131I radioiodine-induced sialadenitis based on the appearances of sialography and sialoendoscopy. Sialoendoscopy can significantly alleviate the clinical symptoms, which is an effective therapy, and better for early lesions.

Inhibitory Effect of Essential Oil from Fructus Alpinia zerumbet on Endothelial-to-mesenchymal Transition Induced by High Glucose via Nrf2/Notch1 Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the inhibitory effect and the possible mechanism of essential oil from fructus Alpinia zerumbet （EOFAZ） on endothelial-to-mesenchymal transition （EndMT） induced by high glucose （HG）. Method:Human umbilical vein endothelial cells （HUVECs） was cultured in vitro to analyze the pharmacodynamic effects of EOFAZ on EndMT and oxidative stress damage induced by HG. The experiment was set the blank group， HG group （35 mmol·L-1）， EOFAZ low dose group （1 μg·L-1） and EOFAZ high dose group （4 μg·L-1）. After EOFAZ intervention for 2 h， HG was added to incubate for 72 h in order to establish EndMT cell model. Western blot was used to detect the protein expression of vimentin and platelet endothelial cell adhesion molecule （CD31）. Angiogenesis experiment was used to detect the ability of cell migration ability in order to analyze the effect of EOFAZ on EndMT. The changes of reactive oxygen species （ROS） levels were detected by 2'，7'-dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescence probe and the contents of malondialdehyde （MDA）， superoxide dismutase （SOD） and catalase （CAT） in cells were detected by the kit method to analyze the effect of EOFAZ on oxidative stress. Western blot was used to detect the protein expression levels of nuclear transcription factor E2 related factor 2 （Nrf2） and Notch1. The overexpression of Nrf2 was achieved by adenovirus （AD） transfection and the mechanism of EOFAZ inhibiting EndMT was further analyzed. The experiment was set the blank group， HG group （35 mmol·L-1）， AD-Nrf2 group， EOFAZ group （4 μg·L-1）， AD-Nrf2+EOFAZ group （4 μg·L-1）. The cells were infected with recombinant adenovirus overexpression plasmid of Nrf2 gene for 6 h， then replaced with normal medium for 24 h. After EOFAZ intervention for 2 h， HG was added to co-incubate for 72 h to induce EndMT. Western blot was used to detect the protein expressions of Nrf2， CD31， vimentin， Notch1 and Snail. Result:Compared with the HG group， after treatment with EOFAZ， the protein expression of CD31 was significantly up-regulated （P<0.05）， the protein expression of vimentin was significantly down-regulated （P<0.01）， the ability of cell migration was decreased （P<0.01）， and the contents of ROS and MDA were decreased （P<0.05， P<0.01）， the levels of CAT and SOD were increased （P<0.01）. In addition， EOFAZ could significantly up-regulate the protein expression of antioxidant signal Nrf2 （P<0.01） and down-regulate the protein expression of Notch1 （P<0.01）. High expression of Nrf2 was achieved by stable AD transfection into HUVECs. The results of Western blot showed that， compared with the HG group， the protein expression levels of Nrf2 and CD31 in each treatment group were significantly increased （P<0.01）， while the protein expression levels of vimentin， Notch1 and Snail were down-regulated （P<0.01）. At the same time， compared with the AD-Nrf2 group， the AD-Nrf2+EOFAZ group could further up-regulate the protein expressions of Nrf2 and CD31 （P<0.05， P<0.01）， while decrease the protein expression levels of vimentin， Notch1 and Snail （P<0.01）. Conclusion:EOFAZ ameliorates oxidative stress injury of vascular endothelial cells induced by HG and inhibits EndMT， which is related to Nrf2/Notch1 signaling pathway.

Clinicopathological characteristics and diagnosis of IgG4related sialadenitis / 北京大学学报(医学版)

Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated disease and one of immunoglobulin G4-related diseases (IgG4-RD). Our multidisciplinary research group investigated the clinicopathological characteristics and diagnosis of IgG4-RS during the past 10 years. Clinically, it showed multiple bilateral enlargement of major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands. The comorbid diseases of head and neck region including rhinosinusitis, allergic rhinitis, and lymphadenopathy were commonly seen, which could occur more early than enlargement of major salivary glands. Internal organ involvements, such as autoimmune pancreatitis, sclerosing cholangitis, and interstitial pneumonia could also be seen. Thirty-five (38.5%) patients had the symptom of xerostomia. Saliva flow at rest was lower than normal. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in almost all the cases and the majority of the patients had increased IgE levels. CT, ultrasonography, and sialography showed their imaging characteristics. Histologically it showed marked lymphoplasmacytic inflammation, large irregular lymphoid follicles with expanded germinal centers, prominent cellular interlobular fibrosis, eosinophil infiltration, and obliterative phlebitis. Their immunohistological examination showed marked IgG-positive and IgG4-positive plasma cell infiltration and high IgG4/IgG ratio. The disease could be divided into three stages according to severity of glandular fibrosis. The serum IgG4 level was higher and the saliva secretion lower as glandular fibrosis increased. IgG4-RS should be differentiated from other diseases with enlargement of major salivary gland and lacrimal gland, such as primary Sjögren syndrome, chronic obstructive submandibular sialadenitis, and eosinophilic hyperplastic lymphogranuloma.

Comparison of the Effect of Endometrectomy and Hysterectomy of Patients with Refractory Menorrhagia / 中山大学学报(医学科学版)

[Objective] To researchthe influence of endometrectomy and hysterectomy on the physiology and mentality of patients with refractory menorrhagia.[Method] This research selected 110 patients with refractory menorrhagia that accepted in our hospital from January,2015 to January,2017 as the object of study.Under the consent of patients,they were randomly divided into the endometrectomy group and hysterectomy group.Then the rate of Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS),the recovery condition of colporrhagia and improvement of anemia of both groups were compared.[Result] Before treatment,the compare between both group's rate of SAS and SDS are not statistically significant (P＞0.05),after treatment,the SAS and SDS rate of endometrectomy group are respectively (45.31±3.58) and (46.31±3.46),which are both significantly lower than the hysterectomy group (P＜0.05);the endometrectomy group has a good rate of 94.55％ on the recovery condition of colporrhagia,which is significantly higher than the hysterectomy group's 81.81％ (P＜0.05);before surgery,the compare of hemoglobin quantity between two group are not statistically significant (P＞0.05);within 1,3 and 6 months after surgery,the hemoglobin level of endometrectomy group are significantly higher than the hysterectomy group (P＜0.05).[Conclusion] Both endometrectomy and hysterectomy can effectively treat patients with refractory menorrhagia,but endometrectomy has less influence on patient's physiology and mentality,which can facilitate patient's recovery and could be widely applied on clinical treatment.

Efficiency and complications of single lacrimal duct intubation versus annular lacrimal duct intubation combined with drugs injection in lacrimal duct obstruction treatment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficiency and complications of single lacrimal duct intubation versus annular lacrimal duct intubation with 5-fluorouracil and tobramycin/dexamethasone eye ointment injection in lacrimal duct obstruction treatment.METHODS:A total of 74 patients (92 eyes) with lacrimal duct obstruction who received surgical treatment by Department of Ophthalmology in Qinhuangdao Haigang Hospital were consecutively recruited between August 2015 and September 2016.They were randomly allocated to Group A or Group B.After probing of lacrimal passage, Group A (46 eyes) were treated by using single lacrimal duct intubation.Group B (46 eyes) were treated by using annular lacrimal duct intubation combined with 5-fluorouracil and tobramycin/dexamethasone eye ointment injection.Between the two groups, Mann-Whitney Rank sum test was used to comparing the operative effect, and Chi-square test was used to comparing the occurrence of complications.RESULTS:The cure rate was 61% in Group A and 89% in Group B;the improvement rate was 22% in Group A and 4% in Group B.Group B had better effect and less complications (2 cases) than Group A (8 cases),the differences between the two groups were significantly(P<0.05).CONCLUSION: Compared with single lacrimal duct intubation, annular lacrimal duct intubation combined with 5-fluorouracil and tobramycin/dexamethasone eye ointment injection has better operative effect and less complication in lacrimal duct obstruction treatment.