Mechanism of Gentisic Acid on Rheumatoid Arthritis Based on miR-19b-3p/RAF1 Axis / 中国结合医学杂志

OBJECTIVE@#To investigate the therapeutic effect of gentisic acid (GA) on rheumatoid arthritis (RA) based on the miR-19b-3p/RAF1 axis.@*METHODS@#The cell counting kit-8 method was used to detect the growth inhibitory effect of different concentrations of GA on MH7A cells, and the drug concentration of GA was determined in the experiment. The quantificational real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-19b-3p and RAF1. RAF1, extracellular regulated protein kinases1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) were examined by Western blotting. Three methods (dual-luciferase assay, qRT-PCR and Western blot analysis) were used to verify miR-19b-3p targeting RAF1. Flow cytometry was performed to detect MH7A cell apoptosis. Transwell and wound healing assays were used to determine the invasion and migration capacities of MH7A cells.@*RESULTS@#The growth of MH7A cells was gradually inhibited with increasing GA concentration. When the GA concentration exceeded 80 mmol/L, GA was significantly cytotoxic to MH7A cells, so the half maximal inhibitory concentration of GA for MH7A cells was calculated as 67.019 mmol/L. GA upregulated miR-19b-3p expression, downregulated RAF1 expression, inhibited ERK1/2 phosphorylation, induced MH7A cell apoptosis and suppressed MH7A cell invasion and migration (P<0.05 or P<0.01). RAF1 was identified as the target of miR-19b-3p and reversed inhibitory effects on miR-19b-3p expression (P<0.05 or P<0.01). The miR-19b-3p inhibitor upregulated RAF1 expression and ERK1/2 phosphorylation, suppressed MH7A cell apoptosis and induced MH7A cell invasion and migration (P<0.01).@*CONCLUSION@#GA regulated miR-19b-3p/RAF1 axis to mediate ERK pathway and inhibit the development of RA.

Nardostachys jatamansi， A Medicinal Plant from Qinghai-Tibet Plateau： A Review / 中国实验方剂学杂志

Nardostachyos Radix et Rhizoma is the dry root and rhizome of Nardostachys jatamansi （Valerianaceae） with a long medical history and a broad range of application， which is effective in regulating Qi， relieving pain， resolving depression， and enlivening spleen， as well as dispelling dampness and relieving swelling by external application. It can be used for the treatment of abdominal distension， loss of appetite， and vomiting. Besides， it can also relieve toothache and treat dermatophytosis and pyogenic infection by external use. Moreover， it serves as a common medicinal material in ancient Ayurveda and Unani medical systems in India and also as an ingredient in spices， foods， and cosmetics. Modern pharmacological studies have shown that Nardostachyos Radix et Rhizoma possesses multiple pharmacological activities， such as sedation， anti-epilepsy， anti-convulsion， anti-depression， anti-arrhythmia， anti-malaria， anti-inflammation， anti-bacteria， anti-oxidation， and blood sugar metabolism improvement due to its multiple compounds contained， including terpenes， flavonoids， coumarins， and lignans. The main active components are sesquiterpenoids represented by nardosinone. The pharmacological activities， chemical compositions， and clinical applications of Nardostachyos Radix et Rhizoma have been investigated， but the research on resources， distribution， quality control， cultivation status， and applications are rarely reported. As an important genuine medicinal material from the Qinghai-Tibet plateau， Nardostachyos Radix et Rhizoma is obtained mainly from wild N. jatamansi. Accordingly， the conservation and sustainable utilization of N. jatamansi have attracted much attention all around the world. Based on the resource survey， cultivation research， and relevant literature available， the present study reviewed resources， geographical distribution， chemical compositions， pharmacological activities， quality control， cultivation， and applications of N. jatamansi， aiming to provide references for the conservation and development of N. jatamansi.

Effect of fertilization combinations of nitrogen, phosphorus, and potassium on four phenolic compounds of cultivated Rhodiola crenulata / 中国中药杂志

This study is aimed to explore the effect of nitrogen, phosphorus and potassium combined application on the active components of Rhodiola crenulata. R. crenulata was used as the research object, "3414" fertilization experiment were conducted with regular fertilization of NPK(N 60 kg·hm⁻², P₂O₅ 100 kg·hm⁻²,KCl 160 kg·hm⁻²) to study the effect of different rates of NPK fertilization on the total amount of 4 phenolic constituents of gallic acid, salidroside, tyrol and ethyl gallate through field test. The results show that the content of salidroside was higher in the treatment of N₁P₂K₁ and N₁P₂K₂, andthe total amount of four phenols was higher in the treatment of N₁P₂K₂ and N₂P₂K₂. The suitable level of nitrogen, phosphorus and potassium promoted the accumulation of the 4 kinds of phenols.The amount of fertilizer recommended by the three factor fertilizer effect equation,(N 0 kg·hm⁻²,P₂O₅ 150 kg·hm⁻²,KCl 31.71 kg·hm⁻²) obtained the highest content of salidroside, and it was 1.54%.（N 35.54 kg·hm⁻²,P₂O₅ 150 kg·hm⁻²,KCl 237.73 kg·hm⁻²）obtained the highest content of 4 kinds of phenolic compounds, and it was 1.93%. This study provides a reference for the standardization of artificial planting of endangered Tibetan medicine.

Coronary Computer Tomography Angiography Features and Associated Risk Factors of Coronary Artery Disease in Young Patients With Suspected Coronary Artery Disease / 中国循环杂志

Objectives:To observe the detection rate of coronary artery disease (CAD) by coronary computer tomography angiography (CCTA) in young patients with suspected CAD, and to explore the imaging features and related risk factors of CAD. Methods:Data from 2 099 patients aged≤45 years who underwent CCTA in our hospital due to suspected CAD were retrospectively obtained. The risk factors of CAD in this patient cohort were analyzed, detection rate and imaging features of CAD among≤20, 21~30, 31~40 and 41~45 years subgroups were compared. Presence or absence of coronary plaque, plaque nature and stenosis degree were recorded. Results:CAD was detected in 229(10.9%) out of 2 099 patients. Incidence of male gender, smoking, dyslipidemia, hypertension, diabetes mellitus, and family history of CAD was significantly higher in CAD group than in non-CAD group (P＜0.05~0.001). Detection rate of CAD significantly increased in proportion with increase of age (F=11.4,P＜0.001) and was 3.1%, 6.2%, 9.7% and 12.9%, respectively in the ≤ 20,21-30,31-40 and 41-45 years groups. The proportion of single-vessel disease (72.5%) was significant higher than the multiple lesion (27.5%) in CAD patients (P＜0.001). There were 183 (56.7%) non-calcified plaques including 39(12.1%) low-attenuation plaques and 54(16.7%) mixed plaques, 86(26.6%) calcified plaques including 72(22.3%) spotty calcified plaques in the 323 diseased vessels. Severe stenosis was found in 158(49.0%) vessels. Conclusions:The prevalence of CAD was 10.9% in this young patient cohort with suspected CAD and imaging features were characterized as single-vessel disease and non-calcified plaques. CCTA should be recommended to young patients with suspected CAD, especially in 30-45-year-old male patients with following risk factors:smoking, hypertension, hyperlipidemia, diabetes mellitus and family history of CAD.

Adiponectin is protective against endoplasmic reticulum stress-induced apoptosis of endothelial cells in sepsis

Endoplasmic reticulum (ER) stress is a critical molecular mechanism involved in the pathogenesis of sepsis. Hence, strategies for alleviating this stress may be essential for preventing cardiovascular injuries under sepsis. Adiponectin is secreted by adipocytes and its levels are decreased in sepsis. The purpose of this study was to investigate the protective effects of adiponectin treatment on endothelial cells and its mechanism. Male Wistar rats underwent cecal ligation and puncture (CLP) before being treated with adiponectin (72 and 120 μg/kg). The levels of malondialdehyde (MDA) in plasma, histological structure, and apoptosis of endothelial cells were evaluated. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with adiponectin at 10 and 20 μg/mL for 24 h after stimulation by lipopolysaccharide (LPS). The levels of reactive oxygen species (ROS), ultrastructure, rate of apoptosis, the expression of inositol-requiring enzyme 1α (IRE1α) protein, and its downstream molecules (78 kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and caspase-12) were detected. The results showed that the levels of MDA and ROS induced by CLP or LPS stimulation were increased. Furthermore, endothelial cell apoptosis was increased under sepsis. The IRE1α pathway was initiated, as evidenced by activated IRE1α, increased GRP78, and up-regulated CHOP and caspase-12 in HUVECs. Following treatment with adiponectin, the number of apoptotic endothelial cells was markedly decreased. These findings demonstrated that treatment with adiponectin decreased apoptosis of endothelial cells caused by sepsis by attenuating the ER stress IRE1α pathway activated by oxidative stress.

Evaluation of renal function parameters in acute kidney injury patients secondary to liver cirrhosis / 临床检验杂志

Objective To investigate the clinical application of measurements of neutrophil gelatinase associated lipocalin in serum (sN-GAL) and urine(uNGAL),cystatin C(CysC) and serum creatinine(sCr) in diagnosis of acute kidney injury(AKI) patients secondary to liver cirrhosis (LC).Methods A total of 260 liver cirrhosis patients without AKI (LC group),207 liver cirrhosis patients with AKI (AKI group)and 106 healthy controls(HC group)were included in the study.The levels of sNGAL,uNGAL,serum creatinine(sCr) and cystatin C (CysC) were determined,respectively.The estimated glomerular filtration rate (eGFR) were calculated base on sCr and CysC,named as c-aGFR and CysC-eGFR.The differences and correlation of each observed parameters among the various groups were statistically analyzed,and the effectiveness of these parameters as biomarkers for predicting the development of AKI in these patients with liver cirrhosis were assessed.Results Compared with LC group and healthy control group,the levels of sNGAL,uNGAL,sCr and CysC in AKI group were significantly increased(all P ＜0.01),while the levels of c-aGFR and CysC-eGFR were significantly decreased(all P ＜ 0.01).Along with the progression of AKI stages,the levels of sNGAL,uNGAL,sCr and CysC in the patients were increasing(all P ＜ 0.01),while the levels of c-aGFR and CysC-eGFR were decreasing(all P ＜0.01).Correlation analysis showed that the levels of sNGAL,uNGAL and CysC were positively correlated with sCr(r =0.662,0.672,0.726,all P ＜0.01)and negatively correlated with c-aGFR(r =-0.639,-0.661,-0.732,all P ＜ 0.01).On the contrary,CysC was negatively correlated with sCr (r =-0.711,P ＜ 0.01)and positively correlated with c-aGFR (r =0.736,P ＜ 0.01).ROC curve analysis showed that the area under the curve (AUC) of uNGAL was maximum (0.995) which were significantly higher than that of sNGAL,sCr,c-aGFR,CysC and CysCeGFR(all P ＜ 0.01).The AUC of sNGAL did not present marked difference with that of sCr and CysC (P ＞ 0.05),but-was barely higher than that of c-aGFR and CysC-eGFR (P ＜ 0.05).The diagnostic effectiveness of uNGAL was maximum (0.962),followed by sNGAL(0.920).Conclusion For diagnosis of the development of AKI in the patients with liver cirrhosis,NGAL may be more reliable marker than sCr and CysC,and the detection of uNGAL could be more effective than sNGAL for the diagnosis.

Corrosion behavior and microstructure of biomedical Mg-Zn-Mn-Gd alloys / 中国组织工程研究

BACKGROUND: As a metal internal fixation material, magnesium alloy has more unique advantages, such as biodegradability and elastic modulus. The elastic modulus of magnesium alloy is similar to the compact bone,which is enough to avoid stress-shelter effect. However, biological activity represents bonding ability with the bone in the body for fracture fixation materials, which is of great significance for studies on new kinds of magnesium alloys.OBJECTIVE: To observe the microstructure of Mg-Zn-Gd alloys and to analyze the corrosion products on the material surface after immersed in simulation body fluid.METHODS: The Mg-Zn-Gd alloys were manufactured by the method of fusion casting. Scanning electron microscope with spectrometer was applied to observe microstructure and distribution of precipitated phase and corrosion products of Mg-Zn-Gd alloys in simulated body fluid.RESULTS AND CONCLUSION: The Mg-Zn-Gd alloy was composed of α-Mg solid solution containing Gd and Zn elements and eutectic structure. The eutectic structure was almost feathery, oval-shaped, herringbone-shaped and strip-shaped along the grain boundary. The main ingredients of eutectic structure included Mg, Zn and Gd elements.Deposition layer was composed of O, Mg, Ca and P elements on the surface of Mg-Zn-Gd alloy after 72 hours soak in Hank's solution. X-ray diffraction analysis showed that film layer contained Mg(OH)2 phase, which promoted calcium salt deposition and reduced the corrosion rate. So Mg-Zn-Gd alloy can obtain better biological activity.

Epidemiology and clinical characteristics of patients with glaucoma: An analysis of hospital data between 2003 and 2012.

Purpose: To assess demographic and clinical characteristics of glaucoma patients in an Ophthalmologic Hospital of Jinan, China from 2003 to 2012. Materials and Methods: Medical charts of patients with primary open‑angle glaucoma (POAG), primary angle closure glaucoma (PACG), and secondary glaucoma (SG) were reviewed. The main outcome measures of patients with glaucoma included basic demographic data (age at presentation, gender, and residence), clinical characteristics (admission date, intraocular pressure, and naked vision), and previous history (injury, cardiovascular disease, diabetes mellitus, hypertension, smoking, and alcohol consumption). Results: Data from 1458 glaucoma patients were reviewed, of which PACG and SG patients accounted for 45.40% and 47.19%, respectively. The average age of all patients with glaucoma increased from 56.05 years in 2003 to 57.83 years in 2012, and the proportion of patients from rural areas rose from 46.43% to 59.13% during 10‑year period. Female gender, cardiovascular disease, and hypertension were associated with PACG. POAG was related to smoking and alcohol consumption. There was positive correlation between SG and history of injury and diabetes mellitus. Conclusion: PACG and SG are the major types of glaucoma. Gender, injury, diabetes mellitus, cardiovascular disease, hypertension, smoking, and alcohol consumption were associated with different types of glaucoma.

Role of copper transporter protein in copper accumulation in C6 cells induced by lead exposure / 中国职业医学

OBJECTIVE: To investigate the role of copper transporter protein and copper chaperones in copper accumulation in glioma cell line C6 cells induced by lead acetate exposure. METHODS: i) CCK-8 assay was used to determine the proper lead acetate dose by treating the cells with lead acetate at the final concentration of 0-50 μmol / L for 24. 0 hours. ii) C6 cells were divided into control group and lead-exposure group,treated with 0 and 10 μmol / L lead acetate respectively for24. 0 hours,and then cultured in 2 μmol / L copper chloride for 0. 0,0. 5,1. 0,2. 0,4. 0 and 8. 0 hours; inductively coupled plasma mass spectrometry was used to detect the levels of copper and lead in the cells. Real-time polymerase chain reaction was used to detect the mRNA expression of copper transporter 1( CTR1),divalent metal transporter 1( DMT1),copper-transporting ATPase α polypeptide / β polypeptide( ATP7 A and ATP7B), antioxidant 1 copper chaperone( ATOX1),cytochrome c oxidase copper chaperone( COX17),and copper-chaperone-for-superoxide dismutase( CCS).Laser con-focal microscopy was applied to detect the protein expression of CTR1 and ATP7 A in cells. RESULTS: i) CCK-8assay proved that the 10 μmol / L lead acetate treatment did not affect C6 cells proliferation( P > 0. 05). Thus the final concentration of 10 μmol / L lead acetate was chosen as the treatment dose in later experiments. ii) After 10 μmol / L lead acetate exposure for 24. 0 hours,the lead and copper levels of C6 cells in lead-exposure group were higher than those in the control group( P < 0. 01),but there was no statistical significant difference in the C6 cell survival rate between these two groups( P > 0. 05). After cells were treated with copper,the C6 cell survival rate of lead-exposure group was lower than that in the control group( P < 0. 01). The interactive effect of copper level showed statistical significance between lead exposure and cooper treatment time( P < 0. 01). At the 5 time points from 0. 5-8. 0 hours after exposure to copper,the copper levels in lead-exposure group were higher than those of control group( P < 0. 05). The copper levels in the control group reached a peak after exposure to copper for 2. 0 hours,and maintained at a stable level till the time point of 8. 0hours. The copper levels of lead-exposed groups increased with the increasing time of copper exposure and there was a time-effect relationship,and they reached to the peak at the time point of 8. 0 hours. After 10 μmol / L lead acetate exposure for 24. 0 hours,compared with control group,the CTR1 and DMT1 mRNA relative expression levels in leadexposed group increased by 113. 00% and 36. 00% respectively( P < 0. 01),and the ATP7 A mRNA relative expression level decreased by 25. 00%( P < 0. 01). The protein expression of CTR1 increased by 76. 04%( P < 0. 01),and the protein expression of ATP7 A decreased by 16. 0%( P < 0. 01). There was no significant difference in the mRNA relative expression levels of ATP7 B,ATOX1,COX17 and CCS between the two groups( P > 0. 05). CONCLUSION: Lead acetate exposure can lead to increase accumulation of copper in C6 cells with increasing exposure time showing a time-effect relationship. The increased protein expression of CTR1 and decreased protein expression of ATP7 A might be one of the mechanisms of inducing copper accumulation in cells after the lead acetate exposure.

Effects of hyperbaric oxygen preconditioning on ischemia-reperfusion inflammation and skin flap survival / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperbaric oxygen preconditioning (HBO) is a new method of ischemia preconditioning. In this study, we examined its effects on skin flap survival and the mechanisms involved.</p><p><b>METHODS</b>Thirty-six rats were divided into three groups: HBO preconditioning, control, and sham groups. An extended epigastric adipocutaneous flap based on the right superficial epigastric artery and vein was raised. A 3-hour period of flap ischemia was induced by clamping the pedicle vessels with a microvascular clamp. At the end of ischemia induction, the clamp was removed and the flap was resutured. Rats in the HBO preconditioning group were treated with HBO four times before surgery. Microcirculation in the skin flap was measured on postoperative days 1, 3 and 5. The size of the flap was measured on postoperative day 5, before the animals were sacrificed. Samples of the skin flap were prepared and stained with hematoxylin and eosin. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the flap samples were measured.</p><p><b>RESULTS</b>Surviving flap size was significantly higher in the HBO preconditioning group compared with controls, with a reduced inflammatory response and increased perfusion. IL-1, TNF-α, and IL-6 levels in the HBO preconditioning group were lower than in controls.</p><p><b>CONCLUSIONS</b>HBO preconditioning improved flap survival in this ischemia-reperfusion rat model. The mechanisms responsible for this effect may relate to attenuation of the inflammatory response and increased flap perfusion following HBO preconditioning.</p>

Value and limitations of multislice spiral CT in diagnosing coronary artery stenoses / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the value and limitations of multislice spiral CT in diagnosing coronary artery stenoses.</p><p><b>METHODS</b>A total of 65 patients with known or suspected coronary artery disease were examined by multislice spiral CT (retrospectively ECG-gating; 0.5 s rotation; one-sector reconstruction algorithm; intravenous contrast agent) and the results were compared with quantitative coronary angiography.</p><p><b>RESULTS</b>In the 889 coronary artery segments of 65 patients, 795 could be evaluated by CT (89.4%), 148 out of 167 coronary artery segments with significant stenoses (> or = 50% reduction of vessel diameter) were correctly detected by CT, 597 out of 628 coronary artery segments with normal or mild stenosis (< 50% reduction of vessel diameter) were correctly detected by CT. These values correspond to a sensitivity of 88.6%, specificity of 95.1%, positive predictive value of 82.7%, and negative predictive value of 96.9% for the detection of significant coronary artery stenosis by CT. Adding the 23 coronary artery segments with significant stenosis which could not be judged by CT, the sensitivity of CT for diagnosing coronary stenosis was 77.9%. In the 795 evaluable coronary artery segments, 78 out of 86 coronary artery segments with high-grade stenosis (> or = 75% reduction of vessel diameter) were correctly detected by CT, 692 of 709 coronary artery segments with normal or mild stenosed (< 75% reduction of vessel diameter) were correctly detected by CT. These values correspond to a sensitivity of 90.7%, specificity of 97.6%, positive predictive value of 82.1%, and negative predictive value of 98.9% for the detection of high-grade coronary artery segments stenosis by CT. Adding 13 coronary artery segments with high-grade stenosis which could not be judged by CT, the sensitivity was 78.8%.</p><p><b>CONCLUSION</b>Multislice spiral CT permits the visualization of significant coronary artery stenosis with high accuracy in case of sufficient image quality.</p>