Moxibustion of Zusanli (ST36) and Shenshu (BL23) alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor/glucocorticoids signaling.

OBJECTIVE: To test the hypothesis that moxibustion may inhibit rheumatoid arthritis (RA) synovial inflammation by regulating the expression of macrophage migration inhibitory factor (MIF)/glucocorticoids (GCs). METHODS: Fifty male Sprague-Dawley rats were randomly divided into five groups (n = 10 each): blank Control (CON) group, RA Model (RA) group, Moxibustion (MOX) group, MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) group, and Moxibustion + MIF inhibitor ISO-1 (MOX + ISO-1) group. Rats in the ISO-1 group and ISO-1 + MOX group were intraperitoneally injected with the inhibitor ISO-1. The rats in the RA group, ISO-1 group, MOX group, and ISO-1 + MOX group were injected with Freund's complete adjuvant (FCA) in the right hind footpad to establish an experimental RA rat model. In the MOX group and MOX + ISO-1 group, rats were treated with Moxa. The thickness of the footpads of the rats in each group was measured at three-time points before, after modeling and after moxibustion treatment. The contents of serum MIF, corticosterone (CORT), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected by enzyme-linked immunosorbent assay; and the contents of synovial MIF were detected by Western blot. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes of synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. RESULTS: Moxibustion was found to reduce the level of MIF and alleviate inflammation in RA rats in this study. In addition, after inhibiting the expression of MIF, the level of CORT increased, and the level of TNF-α decreased. Treating RA rats with inhibited MIF by moxibustion, the level of CORT was almost unchanged, but the level of TNF-α further decreased. The correlation analysis data suggested that MIF was positively related to the expression of TNF-α and negatively correlated with the expression of CORT. CONCLUSION: Reducing MIF to increase CORT and decrease TNF-α by moxibustion treatment in RA. MIF may be a factor for moxibustion to regulate the expression of CORT, but the expression of TNF-α is due to the incomplete regulation of the MIF. This study added to the body of evidence pointing to moxibustion's anti-inflammatory mechanism in the treatment of RA.

Herbal Textual Research on Olibanum in Famous Classical Formulas / 中国实验方剂学杂志

By consulting the ancient and moderm literature， this paper makes a textual research on the name， origin， quality evaluation， harvesting and processing of Olibanum， so as to provide a basis for the development of the famous classical formulas containing this medicinal material. According to the herbal textual research， the results showed that Olibanum was first described as a medicinal material by the name of Xunluxiang in Mingyi Bielu（《名医别录》）， until Ruxiang had been used as the correct name since Bencao Shiyi（《本草拾遗》） in Tang dynasty. The main origin was Boswellia carterii from Burseraceae family. The mainly producing areas in ancient description were ancient India and Arabia， while the modern producing areas are Somalia， Ethiopia and the southern Arabian Peninsula. The medicinal part of Olibanum in ancient and modern times is the resin exuded from the bark， which has been mainly harvested in spring and summer. It is concluded that the better Olibanum has light yellow， granular， translucent， no impurities such as sand and bark， sticky powder and aromatic smell. There were many processing methods in ancient times， including cleansing（water flying， removing impurities）， grinding（wine grinding， rush grinding）， frying（stir-frying， rush frying， wine frying）， degreasing， vinegar processing， decoction. In modern times， the main processing methods are simplified to cleansing， stir-frying and vinegar processing. Nowadays， the commonly used specifications include raw， fried and vinegar-processed products. Among the three specifications， raw products is the Olibanum after cleansing， fried products is a kind of Olibanum processed by frying method， vinegar-processed products is the processed products of pure frankincense mixed with vinegar. Based on the research results， it is recommended to select the resin exuded from the bark of B. carterii for the famous classical formulas such as Juanbitang containing Olibanum， processing method should be carried out in accordance with the processing requirements of the formulas， otherwise used the raw products if the formulas without clear processing requirements.

Efficacy of electroacupuncture stimulating Zusanli (ST36) and Xuanzhong (GB39) on synovial angiogenesis in rats with adjuvant arthritis.

OBJECTIVE: To investigate the efficacy of electroacupuncture (EA) stimulating Zusanli (ST36) and Xuanzhong (GB39) on synovial angiogenesis in rats with adjuvant arthritis (AA). METHODS: AA models were established by bilateral injection of Freund's complete adjuvant (FCA) in male Sprague-Dawley rats. Three days after injection, rats were given EA at Zusanli (ST36) and Xuanzhong (GB39) acupoints, once every other day, for 16 d. The arthritis index score, paw volume, and hematoxylin-eosin (HE) staining was performed for each animal. Angiogenesis marker cluster of differentiation 34 (CD34) expression and synovial cell apoptosis in synovial tissue were observed. The levels of Notch1, hairy and enhancer of split homolog-1 (Hes1), transforming growth factor-beta (TGF-ß) and basic fibroblast growth factor (bFGF) were subsequently detected. RESULTS: We found that EA significantly decreased arthritis index scores, paw volume, and HE staining scores. EA could significantly inhibit the expression of CD34, promoting apoptosis of synovial cells in the joint synovial tissue of AA rats. The expression of Notch1 signaling pathway proteins and mRNAs (Notch1, Hes1, TGF-ß, and bFGF) were markedly downregulated by EA treatment. CONCLUSIONS: These results prove that EA attenuates synovial angiogenesis by inhibiting the Notch1 signaling pathway in AA rat models. Based on our findings, we propose that EA is a promising complementary and alternative therapy in rheumatoid arthritis.

Herbal Textual Research on Eucommiae Cortex in Famous Classical Formulas / 中国实验方剂学杂志

In order to provide the basis for the development of famous classical formulas， the name， origin， quality evaluation， harvesting and processing of Eucommiae Cortex were systematically researched by consulting the ancient herbal and medical books， combining with the modern literature. According to the textual research， materia medica in the past dynasties used Eucommiae Cortex as the correct name. Combined with characteristics， origin and efficacy， Eucommiae Cortex in ancient times to the present is the dry bark of Eucommia ulmoides from family Eucommiaceae. The earliest producing areas of Eucommiae Cortex are Henan， Shanxi， Shaanxi and Sichuan. Since the Ming dynasty， the producing areas have expanded to most of the regions in the country， and Sichuan， Shaanxi， Chongqing， Guizhou and Hubei are regarded as the authentic producing areas. It has been concluded that the quality of Eucommiae Cortex is best if the bark has thick body， large block， scraped rough skin， multi silk section and dark purple internal surface. In ancient times， the processing methods of Eucommiae Cortex were mainly included removing rough bark and cutting for raw use， processing with auxiliary materials such as honey， ginger juice， salt water， wine， and so on. While in modern times， the processing methods have become increasingly simplified which are mainly cutting raw materials after cleansing and salt processing. It is need to excavate the connotation of different processed products and restore the traditional main processing methods through standards. Based on the requirement of Eucommiae Cortex in Sanbitang， it is suggested to use ginger-processed products according to the research results， which is used ginger juice as auxiliary material and processed with stir frying method according to the 2020 edition of Chinese Pharmacopoeia.

Efficacy of Moxa-burning heat stimulating Zusanli (ST36) and Shenshu (BL23) on expressions of macrophage migration inhibitory factor and macrophage apoptosis in rabbits with adjuvant-induced arthritis.

OBJECTIVE: To evaluate the effects of moxa-burning heat stimulating acupoints Zusanli (ST36) and Shenshu (BL23) on macrophage migration inhibitory factor (MIF) and its related molecules which can provide scientific experimental basis for the clinical application of moxibustion treatment of rheumatoid arthritis (RA). METHODS: Thirty rabbits were randomly assigned to control group, RA model (established by injecting Freund's Complete Adjuvant) group (RA group) and RA model with moxibustion group [Moxa group, Zusanli (ST36) and Shenshu (BL23), 5 moxa pillars/day, 6 d × 3]. The expressions of MIF mRNA were evaluated with reverse transcription polymerase chain reaction; the apoptosis rates of macrophages were detected by erminal deoxynucleotidyl transferase-mediated dTUP nick end labeling; the expressions of related signal molecules were detected with immunohistochemical S-P method and the levels of IL-2 were detected with enzyme-linked immunosorbent assay. RESULTS: The expressions of MIF mRNA, extracellular regulated protein kinases 2, p38 mitogen-activated protein kinase and nuclear factor-κ-gene binding p65 in synovial tissue of RA group were significantly increased when compared with control group, which were lower remarkably in moxa group than those in RA group. The apoptosis rates of macrophages in RA group were significantly down-regulated as compared with the control group, which were up-regulated in moxa group compared with the RA group. The levels of IL-2 in synovial fluid from the RA group were elevated significantly as compared with that from control group, but those of the moxa group were reduced when compared with those from RA group. CONCLUSIONS: Moxibustion may simultaneously regulate the expressions of MIF and its related signaling pathways molecules, the apoptosis rate of macrophages in synovial tissue, as well as the level of inflammatory factors in synovial fluid. The results suggest that the anti-inflammatory effect of moxibustion on RA may be related to inhibit the expression of MIF in synovial tissue, the molecules of some related signaling pathways and promote the apoptosis of macrophage.

Research progress of receptor ，pathway and pharmacological effect of 3-iodothyronine / 中国药房

3-iodothyronamine（T1AM）is an endog enous derivative of thyroid hormone. It can also be used as exogenous drug. It can play pharmacological effects such as reducing cardiac output and coronary flow ，slowing heart rate ，promoting lipolysis ， reducing basic metabolism and improving learning and memory ability. Its regulatory effect on metabolism is similar to that of thyroxine，but regulatory effect on heart and thermogenic function is opposite to that of thyroxine. As a new chemical messenger ， T1AM can exert different pharmacological effects through a variety of receptors and signal pathways. This review summarizes the research progress of various pharmacological effects and mechanisms of exogenous T 1AM，in order to provide new therapeutic drugs of cardiovascular ，metabolic diseases and nervous system diseases.

MicroRNA-26a-5p protects against podocyte injury via inhibiting TRPC6 expression in diabetic kidney disease / 中华肾脏病杂志

Objective:To investigate the protective effect and potential mechanisms of microRNA-26a-5p (miR-26a-5p) on podocyte injury in diabetic kidney disease (DKD).Methods:(1) In vivo experiment: Four-week-old db/db mice were divided into db/db group, db/db+agomir-NC group and db/db+miR-26a-5p agomir group according to random number table method, with 10 mice in each group, and 10 db/m mice of the same week-old were set as normal control group. At the age of 10 weeks, pathological changes were observed through light and electron microscopy. Kidney weight/body weight (KW/BW), urinary albumin to creatinine ratio (ACR), fasting blood glucose (FBG) and other biochemical indicators were also detected. The position and expression of miR-26a-5p in kidney tissue were determined through fluorescence in situ hybridization and quantitative real-time PCR, while the expressions of transient receptor potential cation channel-6 (TRPC6) and Nephrin in kidney tissue were determined by Western blotting and immunohistochemistry. (2) In vitro experiment: The immortalized mouse podocytes (MPC5) were divided into 5 groups: normal glucose group, high mannitol group, high glucose group, high glucose+miR-26a-5p mimic group, and high glucose+mimic-NC group. The expressions of miR-26a-5p, TRPC6 and Nephrin were detected. Luciferase reporter assay was conducted to research the relationship of miR-26a-5p and TRPC6. Results:(1) In vivo experiment: Compared with db/m group, db/db mice exhibited lower KW/BW and disrupted conditions of ACR, FBG, total cholesterol, triglycerides and low density lipoprotein cholesterol (all P<0.01). Increased glomeruli volume, more extracellular matrix deposition, thicker basement membrane and more foot process fusion were observed by light and electron microscope. Increased expression of TRPC6 protein as well as decreased expression of Nephrin protein and miR-26a-5p were detected in kidney tissues of db/db mice ( P<0.05). Compared with db/db+agomir-NC group, db/db mice transfected by miR-26a-5p agomir exhibited less albuminuria, with less protein expression of TRPC6 and more Nephrin in kidney tissue (all P<0.05). (2) In vitro experiment: Compared with normal glucose group, high glucose-treated podocytes exhibited increased expression of TRPC6 ( P<0.05), as well as decreased expression of Nephrin ( P<0.05) and miR-26a-5p ( P<0.01). Compared with high glucose+mimic-NC group, lower expression of TRPC6 and higher expression of Nephrin were detected in podocytes transfected by miR-26a-5p mimic (both P<0.05). Luciferase reporter assay confirmed that miR-26a-5p could regulate the expression of TRPC6 precisely. Conclusions:The expression of miR-26a-5p in podocytes is down-regulated in the context of high glucose and miR-26a-5p protects podocytes from injury via inhibiting the expression of TRPC6 in DKD.

Research progress of intracameral moxifloxacin in the prevention of bacterial endophthalmitis after cataract surgery / 中华实验眼科杂志

Postoperative endophthalmitis (POE) is a serious vision-threatening complication of cataract surgery, with an incidence rate of 0.033%-0.11% in China.In recent years, numerous retrospective studies and data analyses have reported that intracameral injection of antibiotics can effectively reduce the incidence of bacterial endophthalmitis, which commonly include cefuroxime, vancomycin and moxifloxacin.Globally, due to factors such as the availability, cost-effectiveness, and types of pathogens of POE, the drug choice varies to a large extent.Adverse events caused by antibiotics in the intracameral injection often occur, including macular edema, retinal vascular leakage, and uveitis caused by overdose of cefuroxime, and complications such as hemorrhagic retinal vasculitis obliterans due to vancomycin.Moxifloxacin, as a fourth-generation fluoroquinolone, has a significant effect on the prevention of bacterial endophthalmitis.Studies in the past five years related to moxifloxacin, and the significant advantages of moxifloxacin in the prevention of bacterial endophthalmitis, drug safety, duration of intracameral drug, and cost-effectiveness were summarized in this article.

Analysis of the awareness rate and the influencing factors of extended prescription policy of contracted residents in the outer suburbs of Shanghai / 中华医院管理杂志

Objective:To investigate the awareness rate of " 1+ 1+ 1" contracted residents in the outer suburbs of Shanghai on the extended prescription policy of the family doctor contract service, and to analyze the influencing factors.Methods:From March to May, 2021, the cluster random sampling method was used to select one community health service center in Fengxian district, Shanghai, and a smart voice telephone assistant survey was conducted among the contracted residents aged 18 and above in the area, to understand their awareness of the extended prescription policy. χ2 Test was used for single factor analysis on the influence of different factors on the policy awareness of the contracted residents, while a multivariate analysis was performed by binary logistic regression, presenting P<0.05 as statistically significant. Results:A total of 13 495 " 1+ 1+ 1" contracted residents were surveyed via phone calls. Their awareness rate of extended prescription policy was 67.5% (9 115/13 495), while those with higher awareness rates were patients with ≥2 chronic diseases (92.3%), patients with 1 chronic disease (88.5%) and those aged 81 and above (88.4%). Logistic regression analysis showed that age, marital status, the number of chronic diseases and signing duration were all independent factors influencing the awareness of extended prescription policy (all P<0.05), while whether the residents were key population groups presented no significant influence on the awareness of extended prescription policy ( P=0.431). Conclusions:The awareness rate of " 1+ 1+ 1" contracted residents in the outer suburbs of Shanghai to the extended prescription policy needs to be further improved and publicity should also be strengthened to extend the policy benefit coverage.

Clinical and imaging characteristics of 107 patients with linear morphea: a retrospective analysis / 中华皮肤科杂志

Objective:To analyze clinical, laboratory and imaging characteristics of different subtypes of linear morphea (LM) , and to propose an appropriate approach to the diagnosis and severity assessment of LM.Methods:Clinical data were collected from patients with clinically and/or pathologically confirmed LM in Department of Dermatology, West China Hospital, Sichuan University from January 2018 to December 2019, and retrospectively analyzed.Results:A total of 107 patients with LM were enrolled into this study, including 63 with LM of the limbs/trunk, 22 with morphea en coup de sabre, 11 with progressive hemifacial atrophy and 11 with eosinophilic fasciitis. Disease severity was evaluated by using the modified localized scleroderma skin severity index (mLoSSI) and localized scleroderma skin damage index (LoSDI) scores in 88 patients, with the mLoSSI scores ranging from 0 to 51 points, and the LoSDI scores ranging from 0 to 40 points. Routine blood examination of 10 patients with eosinophilic fasciitis showed increased eosinophil counts in 4 patients. Thirteen (14.8%) of 88 patients with LM were positive for antinuclear antibody, with titers of ≥ 1∶320. Magnetic resonance imaging (MRI) examination showed ipsilateral cerebral hemisphere atrophy and contralateral white matter hyperintensity on T2-weighted images in 2 out of 4 patients with progressive hemifacial atrophy, myofascial thickening in 26 out of 28 patients with LM of the limbs/trunk (92.9%) , subcutaneous septal and myofascial thickening in all 11 patients with eosinophilic fasciitis.Conclusions:The preliminary assessment of disease activity, severity and prognosis of LM can be made by mLoSSI and LoSDI. MRI examination is recommended for patients with clinical signs of involvement of subcutaneous structures.

Effect of Portulacae Herba free granuleson integrin-β1 of rats’ lens with diabetic cataract / 国际中医中药杂志

Objective:To investigate the effect of Portulacae Herba free granules on the degree of lens opacity and integrin β1 of lens in diabetic cataract rats. Methods:50 rats were randomly divided into control group, model group and the low, medium and high dose group of Portulacae Herba, 10 rats in each group. Except the control group, the diabetic cataract rat model was established by intraperitoneal injection of 1% STZ 60 mg/kg. The low, medium and high dose groups of Portulacae Herba were gavaged with Portulacae Herba 125, 250, 500 mg/kg, once a day for 12 weeks. The degree of lens opacity was observed with slit lamp. After 12 weeks, the lens was stained with HE. The expression of integrin β1 was detected by Western blot.Results:Compared with the model group, the opacification degree of lens in the low, medium and high dose groups of Portulacae Herba was significantly decreased ( P<0.05), the expression of integrin β1 (1.58 ± 0.14, 1.46 ± 0.24, 1.12 ± 0.19 vs. 1.76 ± 0.23) in rat lens was decreased ( P<0.05). Conclusion:For diabetic cataract rats, Portulacae Herba free granules can influence the expression of integrin β1 and inhibit the occurance of lens opacity.

Comparative Transcriptome Analysis Reveals the Potential Cardiovascular Protective Targets of the Thyroid Hormone Metabolite 3-Iodothyronamine (3-T1AM).

BACKGROUND: The thyroid hormone metabolite 3-iodothyronamine (3-T1AM) is rapidly emerging as a promising compound in decreasing the heart rate and lowering the cardiac output. The aim of our study was to fully understand the molecular mechanism of 3-T1AM on cardiomyocytes and its potential targets in cardiovascular diseases. MATERIALS AND METHODS: In our study, we utilized RNA-Seq to characterize the gene expression in H9C2 cells after 3-T1AM treatment. Comparative transcriptome analysis, including gene ontology, signaling pathways, disease connectivity analysis, and protein-protein interaction networks (PPI), was presented to find the critical gene function, hub genes, and related pathways. RESULTS: A total of 1494 differently expressed genes (DEGs) were identified (192 upregulated and 1302 downregulated genes) in H9C2 cells for 3-T1AM treatment. Of these, 90 genes were associated with cardiovascular diseases. The PPI analysis indicated that 5 hub genes might be the targets of 3-T1AM. Subsequently, eight DEGs characterized using RNA-Seq were confirmed by RT-qPCR assays. CONCLUSIONS: Our study provides a comprehensive analysis of 3-T1AM on H9C2 cells and delineates a new insight into the therapeutic intervention of 3-T1AM for the cardiovascular diseases.

Resveratrol protects human retinal pigment epithelial cells from toxicity of high glucose by up-regulation of miR-26a / 中国临床药理学与治疗学

AIM: To study the protective effects and mechanism of resveratrol (RES) on the injury of human retinal pigment epithelial cells (ARPE-19) induced by high glucose (HG). METHODS: ARPE-19 cells were cultured in HG to simulate injury. Cell viability, apoptosis, ROS generation and miR-26a level were examined by CCK-8 assay, flow cytometry assay, DCFH-DA staining and RT-qPCR, respectively. Expression of proteins associated with viability, apoptosis and oxidative stress was measured by Western blot analysis. In addition, the involvements of the ERK and Wnt/β-catenin pathways were analyzed by Western blot analysis.RESULTS:HG reduced cell viability while promoted apoptosis and oxidative stress in ARPE-19 cells. RES ameliorated HG-induced cell injury. The expression of miR-26a was up-regulated by RES in HG-treated cells, and miR-26a inhibition obviously reversed the effects of RES on HG-treated cells. Finally, we found the ERK and Wnt/β-catenin pathways were inhibited by RES through up-regulation of miR-26a. CONCLUSION: RES protected ARPE-19 cells against HG-induced injury through up-regulating miR-26a, along with inhibition of the ERK and Wnt/β-catenin pathways. RES might be a potential therapeutic drug for diabetic retinopathy.

Quality Comparison of Ziziphi Spinosae Semen under Different Packaging and Storage Conditions / 中国药房

ABSTRACT OBJECTIVE：To determine the suitable storage conditions，packaging materials and packaging methods of Ziziphi Spinosae Semen，and to provide reference for guaranteeing the quality. METHODS：The same batch of Ziziphi Spinosae Semen samples were packed in plastic woven bag，plastic bag，plastic bag in vacuum，aluminum-plastic composite bag，aluminum-plastic composite bag in vacuum and kraft coated paper bag. They were stored in a cool warehouse（temperature ≤20 ℃，relative humidity was 45％-75％） and drug stability test box [temperature was（40±2）℃，relative humidity was（75±5）％]. Five evaluation indexes were detected during 6-month of long-term cool stability test and accelerated stability test，including characters and the contents of moisture，aflatoxins，jujubosides A and spinosin. RESULTS：The results of 6-month long-term cool stability test showed that the character and the content of moisture，aflatoxins and jujubosides A of Ziziphi Spinosae Semen under different packaging conditions were in line with the requirements of 2015 edition of Chinese Pharmacopeia （part Ⅰ）（shorted for “pharmacopeia”）. The content of spinosin didn’t meet the requirement of pharmacopeia（no less than 0.080％），but the content of spinosin（0.079％）of aluminum-plastic composite bag in vacuum was close to the requirements of pharmacopeia. The results of 6-month accelerated stability test showed that the sample packed in kraft coated paper bag and plastic woven bag were seriously moldy；the sample packed in plastic bag and plastic bag in vacuum were blackened；the color of the sample packed in aluminum-plastic composite bag was slightly darker；but the appearance of the sample packed in aluminum-plastic composite bag in vacuum was basically unchanged. Only when stored for 2-month，the content of aflatoxin B1 in the sample packed in plastic woven bag was 8.64 μg/kg，which exceeded the pharmacopoeia regulation. The moisture content of the sample packed in plastic woven bag and kraft coated paper bag exceeded the highest value （9.0％） required by the pharmacopoeia. Although the content of jujuboside A of samples in each package decreased，it meet the requirements of the pharmacopoeia. Only the content of spinosin （0.084％）of sample packed in plastic bag in vacuum meet the requirements of the pharmacopoeia，and the content of spinosin （0.071％）of sample packed in aluminum-plastic composite bag in vacuum was relatively high. CONCLUSIONS：Ziziphi Spinosae Semen should be stored in a cool and dry place after packed in aluminum-plastic composite bag in vacuum.

Characteristics of plasma exosome in rheumatoid arthritis and its effect on the function of human vascular endothelial cells / 中华风湿病学杂志

Objective:To investigate the effect of plasma-derived exosomes on the function of human venous endothelial cells in normal and rheumatoid arthritis patients.Methods:The plasma of healthy controls and rheumatoid arthritis patients was collected, and the surface protein markers were identified by transmission electron microscopy (TEM) and NTA. The effects of exosomes on endothelial cell proliferation and migration and invasion were detected by CCK8, cell scratch, Transwell chamber experiments; real time polymerase chain reaction (RT-PCR). The changes of cell secretion hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) content were detected. The comparison between the two groups was performed by t test. Results:The double concave disc-like cystic vesicles were observed by transmission electron microscopy, nanoparticle tracking analysis (NTA) showed that the diameter was about 50-150 nm. Western blotting showed that the relative molecular weights of flotillin1 and CD81, on the surface of plasma exosomes were 47 000 and 26 000, respectively. Endothelial cell activity decreased with the increase of exosomes concentration, but the difference between the two groups was not significant( t=1.86, P>0.05). Compared with normal human con-exo, ra-exo significantly inhibited endothelial cell migration [(2.24±0.23) vs (1.46±0.13), t=6.60, P<0.05], reduced invasive capacity [(0.673±0.030) vs (0.827±0.030), t=8.11, P<0.05] in patients with rheumatoid arthritis. In addition, the ability to secrete HIF-1a, VEGF cytokines was decreased significantly, the difference was statistically significant [(0.706±0.020) vs (0.908±0.040), t=10.10, P<0.05; (0.692±0.010) vs (0.841±0.020), t=14.90, P<0.05]. Conclusion:The exosomes from plasma may play an important role in RA and vascular injury.

Expressions of aldehyde dehydrogenase 1 and ATP-binding cassette superfamily G member 2 in non-small cell lung cancer and their clinical significances / 肿瘤研究与临床

Objective:To explore the expression levels of aldehyde dehydrogenase 1 (ALDH1) and ATP-binding cassette superfamily G member 2 (ABCG2) in non-small cell lung cancer (NSCLC) tissues, and to observe the correlations of their expressions with clinicopathological features and prognosis of patients.Methods:The tissue samples from 82 patients with NSCLC who underwent surgical treatment from January 2016 to November 2018 in Taishan Hospital of Shandong Province were selected. The expressions of ALDH1 and ABCG2 in fresh cancer tissues and adjacent tissues were detected by immunohistochemistry. χ 2 test was used to analyze the correlations of ALDH1 and ABCG2 expressions with clinicopathological features of patients; Pearson method was used to analyze the correlation between ALDH1 and ABCG2; Kaplan-Meier method and log-rank test was used to analyze the correlations of ALDH1 and ABCG2 expressions with the overall survival (OS) of patients; Cox proportional hazards model was used to analyze the influencing factors of OS. Results:The positive expression rates of ALDH1 and ABCG2 in NSCLC tissues were higher than those in adjacent tissues, and the differences were statistically significant [60.98% (50/82) vs. 12.19% (10/82), 51.22% (42/82) vs. 3.66% (3/82), χ 2 values were 42.051 and 46.582, both P < 0.01]. ALDH1 expression was positively correlated with ABCG2 expression in NSCLC tissues (P < 0.05). The positive expression rates of ALDH1 and ABCG2 in patients with TNM stage Ⅱ-Ⅲ were higher than those in patients with stage Ⅰ [70.00% (35/50) vs. 46.88% (15/32), 60.00% (30/50) vs. 37.50% (12/32), both P < 0.05], and the positive expression rates of ALDH1 and ABCG2 in patients with lymph node metastasis were higher than those in patients without metastasis [75.00% (27/36) vs. 50.00% (23/46), 66.67% (24/36) vs. 39.13% (18/46), both P < 0.05]. The median follow-up time was 22.5 months, a total of 2 patients were lost to follow-up, and the median OS time was 25.4 months. The OS rate of ALDH1-positive patients was lower than that of ALDH1-negative patients (χ 2 = 5.124, P = 0.031), and the OS rate of ABCG2-positive patients was lower than that of ABCG2-negative patients (χ 2 = 6.969, P = 0.008). Multivariate Cox analysis showed that age (OR = 1.241, 95% CI 1.021-2.535, P = 0.045), lymph node metastasis (OR = 1.521, 95% CI 1.102-4.281, P = 0.012), TNM stage (OR = 2.104, 95% CI 1.289-6.150, P = 0.018), ALDH1 (OR = 2.435, 95% CI 1.214-8.654, P = 0.001), and ABCG2 (OR = 1.503, 95% CI 1.148-5.696, P = 0.021) were independent influencing factors of OS for patients with NSCLC. Conclusions:The expressions of ALDH1 and ABCG2 in NSCLC tissues are increased, and they are associated with lymph node metastasis and TNM staging. The OS rate in ALDH1-positive and ABCG2-positive patients is low. ALDH1 and ABCG2 may be prognostic markers for NSCLC.

Study on iTRAQ-based differential expression protein analysis in nuclear cataract lens with different axial length / 中华实验眼科杂志

Objective@#To identify and verify differentially expressed proteins in lens of nuclear cataract eyes with different axial lengths.@*Methods@#Forty-eight nuclear cataract patients with the hardness grade Ⅲ to Ⅳ were enrolled from January 2016 to December 2017 in the east area of Xining city.The lens nucleus was obtained during extracapsular cataract extraction (ECCE) surgery.The samples were divided into six groups according to age and axial length, with 8 samples in each group.Seven normal transparent human lens nuclei were obtained from donors during corneal transplantation surgery and served as normal control.Water-soluble, water-insoluble and water-insoluble-urea-soluble protein fractions were extracted separately and merged to analyze by using 8-plex isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with 2D-LC/MS/MS.The data were processed with ProteinPilot software.Two technical replicates of iTRAQ analyses were carried out.Up-regulated and down-regulated proteins were selected in two replicates as candidate biomarkers.Twenty lens nuclei from 20 nulear cataract patients were divided into long axis young age group, normal axis young age group, long axis old age group and normal axis old age group.Western blot was used to confirm the most different proteins.This study protocol was approved by the Ethics Committee of TangDu Hospital of Air Force Medical University (TDLL2015046). Written consent was obtained from each participant.@*Results@#Eighty proteins were identified.Six proteins were selected as differentially-expressed proteins.Sorbitol dehydrogenase (SDH) was elevated whereas beta-crystallin B2 (CRYBB2) was decreased in the long axis groups.The relative expression of SDH protein in the long axis low age group was 1.204±0.142, which was significantly higher than 0.711±0.072 in the normal axis low age group, the relative expression level of SDH in the long axis old age group was 1.092±0.334, which was significantly higher than 0.617±0.089 in the normal axis old age group, the difference was statistically significant (all at P<0.05).@*Conclusions@#The expression levels of SDH in the nuclear cataract were elevated with long axial length.SDH may be involved in the pathogenesis of axial myopia-associated nuclear cataract.

Xiaokeping-induced autophagy protects pancreatic ß-cells against apoptosis under high glucose stress.

Xiaokeping (XKP), a prescribed Traditional Chinese Medicine (TCM), has been used to treat patients with type Ⅱ diabetes mellitus for many years; however, the molecular mechanism of its effects is unknown. As the only insulin producer, the pancreatic ß cell plays an important role in diabetes. Whether XKP influences the viability of pancreatic ß cells remains to be substantiated. In the present study, autophagy/apoptosis analyses were used to evaluate the therapeutic effect of XKP on pancreatic ß-cells induced by high glucose levels and to investigate a potential causal molecular mechanism of XKP effect on the cells. The pancreatic ß-cell lines MIN-6 were divided into four groups: control, high glucose (33.3 mmol/L), high glucose with XKP, high glucose with XKP and 3-Methyladenine (3-MA). Immunofluorescence assay was employed to determine autophagosome formation and flow cytometry was used to determine apoptotic rates of the ß cells by the detecting expression of autophagy- and apoptosis-related proteins. High glucose increased the apoptotic rate of ß-cells from 5.37% to 23.24%; however addition of XKP mitigated the rate at 10.92%. Data indicate that autophagy of ß-cells was induced by XKP via the mammalian target of rapamycin (mTOR) pathway. Where the autophagy inhibitor 3-MA was added, the apoptotic rate was 23.94%, similar to the high glucose group rate. The results suggest a potential cytoprotective effect of XKP from high glucose toxicity by its induction of autophagy which may be linked to mTOR-mediated autophagy.

Early enteral nutrition support dose selection in critically ill patients: a Meta analysis / 中华急诊医学杂志

Objective To systematically evaluate the optimal dose of early enteral nutrition support in critically ill patients.Methods Systematic search database including PubMed,Web of science,Scopus,CINAHL,CBM,CNKI.RCTs about early enteral nutrition dose selections in critically ill patients were chosen according to include and exclude criteria by two researchers independently.Cochrane system evaluation manual bias risk assessment was used to evaluate quality of literature.RevMan5.3 Meta analysis software was used to analyze the data.Results A total of 1 571 literatures were retrieved and 8 RCT studies were included,2 713 subjects in total.Meta analysis results showed that there were statistically significant differences in mechanical ventilation time,incidence of diarrhea,and utilization rate of gastro dynamic drugs between trophic feeding and full feeding (P＜0.05).There were no statistically significant differences in mortality,length of stay,incidence of nosocomial infections,reflux,vomiting,constipation,etc.(P＞0.05).Conclusions Trophic feeding has familiar effects on mortality,length of hospital stay compared to full feeding,but it can help to shorten ICU mechanical ventilation time,improve the gastrointestinal tolerability.

Role of Akt/mTOR signaling pathway in ulinastatin-induced reduction of oxidative stress injury to cardiomyocytes of rats / 中华麻醉学杂志

Objective To evaluate the role of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ulinastatin-induced reduction of oxidative stress injury to cardiomyocytes of rats.Methods H9c2 cells were inoculated in 96-well plates at a density of 104 cells/well.The cells were divided into 5 groups using a random nomber table:control group (group C,n =12),H2O2 group (n=12),H2O2 plus ulinastatin group (group HU,n=12),H2O2 plus ulinastatin plus LY294002 group (group HUL,n=9) and H2O2 plus LY294002 group (group HL,n=9).In group H2O2,H2O2 (final concentration 200 μ mol/L) was added,and the cells were incubated for 12 h in the incubator.In HU,HL and HUL groups,ulinastatin (final concentration 50 U/ml),LY294002 (final concentration 10 μmol/L),and ulinastatin (final concentration 50 U/ml) plus LY294002 (final concentration 10 μmol/L)were added,respectively,the cells were incubated for 2 h,H2O2 (final concentration 200 μmol/L) was then added,and the cells were incubated for 12 h in the incubator.The cell survival rate was measured by methyl thiazolyl tetrazolium assay.The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by using water soluble tetrazolium-1 and thiobarbituric acid colorimetric assays.Cell apoptosis was measured by flow cytometry,and apoptosis rate (AR) was calculated.The expression of Akt,phosphorylated Akt (p-Akt),mTOR,phosphorylated mTOR (p-mTOR),activated caspase-3 and activated poty-ADP-ribose polymerase (PARP) was detected by Western blot.The p-Akt/AKT and pmTOR/mTOR ratios were calculated.Results Compared with group C,the cell survival rate was significantly decreased,AR was increased,the SOD activity was decreased,the MDA content was increased,the expression of activated caspase-3 and PARP was up-regulated (P＜0.05),and no significant change was found in p-Akt/AKT ratio or p-mTOR/mTOR ratio in group H2O2 (P＞0.05).Compared with group H2O2,the cell survival rate was significantly increased,AR was decreased,the SOD activity was increased,the MDA content was decreased,the p-Akt/AKT and p-mTOR/oTOR ratios were increased,and the expression of activated caspase-3 and PARP was down-regulated in group HU (P＜0.05).Compared with group HU,the cell survival rate was significantly decreased,AR was increased,and the expression of activated caspase-3 and PARP was up-regulated in group HUL (P＜0.05).Conclusion The mechanism by which ulinastatin reduces oxidative stress injury to cardiomyocytes is related to activation of Akt/mTOR signaling pathway in rats.