The efficacy and safety of intravenous sucrose iron therapy for recurrent iron deficiency anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Mechanism of omege-6 PUFA increasing the susceptibility to acute myocardial ischemia injury / 药学学报

The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.

Research progress on the detection methods and their application in ferroptosis / 药学学报

Ferroptosis is a novel type of cell death, which is distinguished from the traditional cell death pathways such as apoptosis, proptosis, necrosis and autophagy in terms of morphology, biochemistry and genetics. The main features of ferroptosis are the iron accumulation and lipid peroxidation. The regulation mechanism of ferroptosis involves glutathione metabolism, lipid peroxidation reactions and iron metabolism, which are closely related to the pathological process of tumor, aging, neurodegenerative diseases, ischemia reperfusion injury, cardiovascular and cerebrovascular diseases, kidney injury, hepatic fibrosis and so on. How to effectively study the role of ferroptosis regulation mechanism in the treatment of diseases becomes the hot spot and focus of the ferroptosis research. In recent years, with the in-depth study of ferroptosis, the identification, confirmation and the mechanism of ferroptosis have been developed significantly and have come forth continuously, in the meantime, techniques based on the morphology, biochemistry, molecular biology and genetics have been widely applied in the detection of ferroptosis. In order to deepen readers' understanding of ferroptosis and its detection methods, this paper will mainly review the current research progress on the detection methods and their application in ferroptosis, summarize and discuss their advantages and disadvantages in the detection of ferroptosis, this knowledge are crucial for better understanding and studying the biological function of ferroptosis.

A modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane (with video demonstration) / 器官移植

Objective To modify the mouse model of orthotopic left lung transplantation from different perspectives, aiming to establish a simpler, faster and stabler mouse model of lung transplantation. Methods Based on preliminary modified rat model of orthotopic left lung transplantation established by our team, varying extent of modifications were made regarding the tracheal intubation, cannula preparation and anastomosis procedures of orthotopic left lung transplantation in the recipient mice. Orthotopic left lung transplantation in 40 mice were performed by an operator with microsurgical experience. The dissection of the recipient's hilar structure was carried out at the plane of the hilar clamp model within the reverse-view, and the three branches (left main bronchus, pulmonary artery and pulmonary vein) of the pulmonary hilum were anastomosed in turn by the "pendulum" anastomosis method. The operation time of each procedure was recorded. The recipient mice were sacrificed at postoperative 2 weeks, and the incidence of postoperative complications was recorded. Results Lung transplantation was successfully completed in 40 mice, with no bronchial and vascular tearing or twisting, and no bleeding at the anastomosis site. The overall cardiopulmonary procurement time was (10.7±1.5) min, cannula preparation time was (16.2±1.5) min, cold ischemia time was (25.1±2.4) min, warm ischemia time was (19.4±1.6) min, and the total operation time was (57.2±2.9) min, respectively. During the follow-up from 6 to 14 days after surgery, one recipient mouse died of pleural effusion, probably caused by infection. No pneumothorax, thrombosis or atelectasis was found in the remaining recipient mice during postoperative follow-up. Conclusions The modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane possesses multiple advantages of short operation time, high success rate and few complications, which is expected to become an alternative model of studying pathological changes after lung transplantation and worthy of further application.

Phospholipid peroxidation: a key factor in "susceptibility" to neurodegenerative diseases / 药学学报

The biochemical integrity of the brain is necessary to maintain normal function. Oxidative damage is one of the mortal important reasons leading to the destruction of this integrity. The nervous system is enriched in phospholipid and polyunsaturated fatty acids (PUFAs). Due to the nature of high oxygen-consumption and rich lipids, brain is particularly vulnerable to oxidative damages. Phospholipid peroxidation is one of the results of imbalance in oxidation-antioxidant system. Once the antioxidant system is insufficient to resist oxidative damage, membrane phospholipids will be prone to free radical attack. Phospholipid peroxidation leads to a variety of toxic oxidation products, including membrane damage, mitochondrial dysfunction, rapid accumulation of amyloid, etc. Multiple proteins and nucleic acids can be covalently modified by peroxidation products, resulting in the loss of the protein functions, which eventually triggers programmed cell death and general neuroinflammation in brain, and ends up with an increased susceptibility to neurodegenerative diseases. Based on the knowledge of mechanisms of phospholipid peroxidation, this review focuses on the characteristics of phospholipid peroxidation as a key factor in the development of neurodegenerative diseases, in order to provide theoretical basis for targeted intervention of phospholipid peroxidation as a potential strategy to prevent neurodegenerative diseases.

Development of an eco-friendly and fast HPLC method for quantitative analysis of four nucleosides in Cordyceps and related products / 中国天然药物

An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products (fermented mycelia of Hirsutella sinensis andPaecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column (50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 mL·min

Matrine inhibits proliferation and migration of HepG2 cells by downregulating ERK1/2 signaling pathways

Objective: To research the effect of matrine on the proliferation and migration of HepG2 cells through extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Methods: HepG2 cell was selected and divided into blank control group, experimental group (matrine 1, 2, and 4 mg/mL), and positive control group (PD98059, ERK1/2 inhibitor). MTT measure was used to detect the effective time and concentration which matrine inhibits HepG2 cells. After 24 h, the effect of effective concentration of matrine on the of morphological changing HepG2 cells was observed. The invasion ability was assayed by transwell method, the expression of ERK1/2 and pERK1/2 were detected through Western blot, and reverse transcription polymerase chain reaction was used to test the expression level of ERK1/2 mRNA. Results: With the increase of matrine concentration, the number of adherent HepG2 cells gradually decreased, the morphologic changes gradually became spherical, some cell morphology was incomplete, and even cell fragments appeared. The proliferation and invasion ability of HepG2 cells decreased. The expression of ERK1/2, pERK1/2, and ERK1/2 mRNA downregulated with the increase of matrine concentration (P < 0.05). Conclusion: Matrine inhibits the proliferation and migration of HepG2 cells by downregulating the ERK1/2 signaling pathway.

Study on the correlation between acute radionuclitidis and improved body mass index in intensity-modulated radiation therapy after cervical cancer surgery / 中华放射肿瘤学杂志

Objective To investigate the relationship between the body mass index (BMI)/body mass index improved (BMIIMPd) and the dose of the small intestine as well as the acute radiation colitis in the intensity-modulated radiation therapy after cervical cancer surgery.Methods Thirty-nine cervical cancer patients underwent postoperative adjuvant radiotherapy.All patients received Philips large bore CT scan for enhanced CT scan,target delineation and organ at risk.All patients were treated with a single arc 10 MV VMAT plan.The correlation between the radiation dose of the small intestine and the acute radiation enteritis and BMI/BMIIMPd was analyzed.Results The BMI was calculated as (22.23±2.80) kg/m2,BMIIMPd was (21.49±3.95) kg/m2,the small intestine volume VSI was (1 155.71 ± 419.33)cc3.The volume of the small intestine received more than 10 Gy (V10_SI) VMAT was (66.50± 27.01) ％,and the equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) were (4 098.87± 184.93) cGy and (7.98±8.73)％.One way ANOVA demonstrated that under the VMAT technology,the BMIIMPd,V30,V40,EUD (or=50) and NTCP in the small intestine were the influencing factors of the occurrence of acute radiation enteritis.Conclusions If the improved BMIIMPd is utilized to distinguish the BMI,the high dose area of the small intestine will be larger and the incidence of acute radiation enteritis will be higher for patients with BMIIMPd between 10.1 and 16.9(normal and thin).Conventional BMI cannot be utilized as a basis for the prediction of the incidence of acute radiation enteritis in patients with cervical carcinoma.

Role of ERK signaling protein in morphine preconditioning reducing global ischemia-reperfusion injury in isolated rat hearts / 中国药理学通报

Aim To observe the role of ERK signaling protein in morphine preconditioning reducing global ischemia-reperfusion injury in isolated rat hearts.Methods Adult male Sprague-Dawley rats were distributed into six groups (n =10 for each) using a random number table:control group (CON),ischemia-reperfusion group (I/R),ischemia preconditioning group (IPC),morphine preconditioning group at the concentration of 1 μmol · L-1 (MPC),ERK inhibitor PD98059 + MPC (MPD),and group of ERK inhibitor-PD98059 (PD).The isolated rat hearts were treated on a Langendorff perfusion apparatus system.The coronary effluent was collected at 15 min of equilibration (baseline),5 and 10 min of reperfusion for detection of the activity of LDH.Meanwhile,a water-filled balloon was inserted into the left ventricular for continuous LVDP measurement.The IS and AAR and IS/AAR ratios were observed by TTC.Western blot was used to examine the level of phosphorylated ERK in myocardium.Results As compared with the I/R group,MPC significantly decreased IS and IS/AAR ratio as well as LDH activities at 5 min and 10 min of reperfusion,but improved the LVDP at the end of reperfusion.Moreover,the phosphorylation level of ERK in myocardium was up-regulated by MPC.However,ERK inhibitor PD98059 could block the protective effects of MPC,as indicated by the increased IS and IS/AAR ratio,elevated LDH activity at the reperfusion of 5 and 10 min,and the suppressed LVDP at the end of reperfusion.Furthermore,the MPC-induced phosphorylation of ERK was also reversed by PD98059.Conclusion Morphine preconditioning may confer cardio-protection against the global ischemia-reperfusion injury in rat hearts through enhancing the phosphorylation of ERK.

Simultaneous determination of cordycepin and 2'-deoxyadenosine in Cordyceps genus by online SPE-HPLC / 中国中药杂志

An online SPE-HPLC method for simultaneous determination of cordycepin (3'-deoxyadenosine) and 2'-deoxyadenosine in Cordyceps genus (C. sinensis,C. militaris,Hirsutella sinensis and C. sobolifera) was developed. The samples were enriched on a ZORBAX SB-AQ (4.6 mm×12.5 mm,5 μm) column with isocratic elution by 9% methanol solution. The separation of analytes was performed on a ZORBAX SB-AQ (4.6 mm×150 mm,5 μm) column with gradient elution by 0.1% formic acid solution and methanol (91∶9). The flow rate was 1.0 mL•min⁻¹. Column temperature was 40 ℃ and detection wavelength was 260 nm. This method has been applied for analysis of different Cordyceps genus. The 2'-deoxyadenosine was detected in C. sinensis,Hirsutella sinensis and C. sobolifera. The cordycepin was detected in C. militaris. In summary,the cordycepin chromatographic peak from C. sinensis in some past reports may be the 2'-deoxyadenosine chromatographic peak or the mixture peak of 2'-deoxyadenosine and cordycepin in which 2'-deoxyadenosine content was higher than cordycepin. The developed method is suitable for analysis of cordycepin and 2'-deoxyadenosine in Cordyceps genus.

Sub-anesthesia Dose of Isoflurane in 60% Oxygen Reduces Inflammatory Responses in Experimental Sepsis Models / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sepsis is a major cause of mortality in Intensive Care Units. Anesthetic dose isoflurane and 100% oxygen were proved to be beneficial in sepsis; however, their application in septic patients is limited because long-term hyperoxia may induce oxygen toxicity and anesthetic dose isoflurane has potential adverse consequences. This study was scheduled to find the optimal combination of isoflurane and oxygen in protecting experimental sepsis and its mechanisms.</p><p><b>METHODS</b>The effects of combined therapy with isoflurane and oxygen on lung injury and sepsis were determined in animal models of sepsis induced by cecal ligation and puncture (CLP) or intraperitoneal injection of lipopolysaccharide (LPS) or zymosan. Mouse RAW264.7 cells or human peripheral blood mononuclear cells (PBMCs) were treated by LPS to probe mechanisms. The nuclear factor kappa B (NF-κB) signaling molecules were examined by Western blot and cellular immunohistochemistry.</p><p><b>RESULTS</b>The 0.5 minimum alveolar concentration (MAC) isoflurane in 60% oxygen was the best combination of oxygen and isoflurane for reducing mortality in experimental sepsis induced by CLP, intraperitoneal injection of LPS, or zymosan. The 0.5 MAC isoflurane in 60% oxygen inhibited proinflammatory cytokines in peritoneal lavage fluids (tumor necrosis factor-alpha [TNF-β]: 149.3 vs. 229.7 pg/ml, interleukin [IL]-1β: 12.5 vs. 20.6 pg/ml, IL-6: 86.1 vs. 116.1 pg/ml, and high-mobility group protein 1 [HMGB1]: 323.7 vs. 449.3 ng/ml; all P< 0.05) and serum (TNF-β: 302.7 vs. 450.7 pg/ml, IL-1β: 51.7 vs. 96.7 pg/ml, IL-6: 390.4 vs. 722.5 pg/ml, and HMGB1: 592.2 vs. 985.4 ng/ml; all P< 0.05) in septic animals. In vitro experiments showed that the 0.5 MAC isoflurane in 60% oxygen reduced inflammatory responses in mouse RAW264.7 cells, after LPS stimulation (all P< 0.05). Suppressed activation of NF-κB pathway was also observed in mouse RAW264.7 macrophages and human PBMCs after LPS stimulation or plasma from septic patients. The 0.5 MAC isoflurane in 60% oxygen also prevented the increases of phospho-IKKβ/β, phospho-IκBβ, and phospho-p65 expressions in RAW264.7 macrophages after LPS stimulation (all P< 0.05).</p><p><b>CONCLUSION</b>Combined administration of a sedative dose of isoflurane with 60% oxygen improves survival of septic animals through reducing inflammatory responses.</p>

Effects of zinc-containing magnesium alloys on proliferation of human osteosarcoma U2OS cells in vitro / 中国组织工程研究

BACKGROUND: Alloying can improve the corrosion resistance and slow the degradation of pure magnesium. In addition, increasing studies have shown that zinc has good antitumor effect. OBJECTIVE: To evaluate the effect of zinc-containing magnesium alloy on the proliferation and apoptosis of human osteosarcoma U2OS cells in vitro.METHODS: The corrosion resistance of pure magnesium and different zinc-containing (2%, 4%, 6%) magnesium alloys were observed and compared by the hydrogen release assay in the Hank's solution. MTT assay was used to examine the effects of different zinc-containing magnesium alloy extractions on the proliferation of U2OS cells (or MC3T3-E1 cells) after co-culture of 1, 3, 5 days. After 24-hour co-culture with pure magnesium, different zinc-containing magnesium alloys and titanium alloy extractions, the apoptotic rates of U2OS cells were analyzed by flow cytometry, and the expression of apoptosis-related proteins were detected by western blot assay.RESULTS AND CONCLUSION: The corrosion resistance of pure magnesium was improved after addition of Zn within the initial 100 hours, and the magnesium alloy containing 4% zinc exhibited the optimal corrosion resistance. Different zinc-containing magnesium alloy extractions obviously inhibited the U2OS proliferation in a zinc level-depended manner, and the cytotoxicity of different zinc-containing magnesium alloy extractions to MC3T3-E1 was graded 0-1. Different zinc-containing magnesium alloy extractions could also induce obvious apoptosis in U2OS cells in a zinc level-depended manner. Different zinc-containing magnesium alloy extractions, especially the magnesium alloy containing 4% zinc, up-regulated the expression of p53 and Bax proteins and down-regulated the expression of Bcl-2 protein in U2OS cells, leading to the disorder of Bcl-2/Bax. These findings suggest that different zinc-containing magnesium alloy extractions can inhibit the proliferation and induce apoptosis of U2OS cells in vitro.

Relationship between the status of BRAF V600 and EGFR gene mutation and clinicopathological features in patients with non-small cell lung cancer / 临床与实验病理学杂志

Purpose To study the status of BRAF V600 and EGFR mutations in patients with non-small cell lung cancer (NSCLC) and to examine the relations between them.Methods BRAF V600 and EGFR mutations were detected with DNA sequencing.The relationship between BRAF V600,EGFR mutations and the clinicopathological features were analyzed.Results BRAF V600 mutations were detected in 11 (7.5％) of the 146 specimens.BRAF V600 mutations were found morelfrequently in non-smokers (P =0.045).There were no significant differences in age,gender,histological subtype and differentiation between patients with and without BRAF V600 mutations (P ＞ 0.05).EGFR mutations were detected in 68 (46.6％) of the 146 specimens.EGFR mutations were found more frequently in women,non-smokers and adenocarcinoma (P ＜ 0.05).Four tumors with BRAF V600 mutations (three V600 and one V600D) showed concomitant EGFR mutations (two DEL and two L858R).Conclusion BRAF V600 mutations in patients with NSCLC are found more frequently in non-smokers.There are no significant differences in age,gender,histological subtype and differentiation between patients with and without BRAF mutations.

Effects of zinc-containing magnesium alloys on proliferation of human osteosarcoma U2OS cells in vitro / 中国组织工程研究

BACKGROUND: Alloying can improve the corrosion resistance and slow the degradation of pure magnesium. In addition, increasing studies have shown that zinc has good antitumor effect. OBJECTIVE: To evaluate the effect of zinc-containing magnesium alloy on the proliferation and apoptosis of human osteosarcoma U2OS cells in vitro.METHODS: The corrosion resistance of pure magnesium and different zinc-containing (2%, 4%, 6%) magnesium alloys were observed and compared by the hydrogen release assay in the Hank's solution. MTT assay was used to examine the effects of different zinc-containing magnesium alloy extractions on the proliferation of U2OS cells (or MC3T3-E1 cells) after co-culture of 1, 3, 5 days. After 24-hour co-culture with pure magnesium, different zinc-containing magnesium alloys and titanium alloy extractions, the apoptotic rates of U2OS cells were analyzed by flow cytometry, and the expression of apoptosis-related proteins were detected by western blot assay.RESULTS AND CONCLUSION: The corrosion resistance of pure magnesium was improved after addition of Zn within the initial 100 hours, and the magnesium alloy containing 4% zinc exhibited the optimal corrosion resistance. Different zinc-containing magnesium alloy extractions obviously inhibited the U2OS proliferation in a zinc level-depended manner, and the cytotoxicity of different zinc-containing magnesium alloy extractions to MC3T3-E1 was graded 0-1. Different zinc-containing magnesium alloy extractions could also induce obvious apoptosis in U2OS cells in a zinc level-depended manner. Different zinc-containing magnesium alloy extractions, especially the magnesium alloy containing 4% zinc, up-regulated the expression of p53 and Bax proteins and down-regulated the expression of Bcl-2 protein in U2OS cells, leading to the disorder of Bcl-2/Bax. These findings suggest that different zinc-containing magnesium alloy extractions can inhibit the proliferation and induce apoptosis of U2OS cells in vitro.

Dynamic expression level of plasma HMGB 1 and clinical significance in patients with sepsis shock / 国际检验医学杂志

Objective To explore the dynamic change of high mobility group box-1(HMGB1) expression in sepsis shock patients and its relationship with prognosis.Methods A total of 98 patients with septic shock in ICU from March 2014 to March 2016 were collected as the research subjects and divided into the shock group (48 cases) and control group(50 cases) according to whether de-veloping shock at admission.The HMGB1 levels and APACHE Ⅱ scores change within 28 d after admission were compared be-tween the two groups ;the shock group was divided into the group A (HMGB1≤35 pg/mL ,30 cases) ,B(HMGB1>35 pg/mL ,18 cases) according to the HMGB1 level before treatment ,the two groups were observed for 3 months from the day admitted to hospi-tal.The APACHEⅡ score ,ScvO2 ,lactic acid concentration and lactic acid clearance rate after 7 d treatment ,ICU mechanical venti-lation use rate and survival rate within 3 months were compared between the two groups.Results The HMGB1 level and A-PACHEⅡ scores before admission had no statistical difference between the shock group and control group (P>0.05);the HMGB1 and APACHEⅡ scores on 7 ,14 ,21 ,28 d after admission in the shock group were significantly higher than those in the control group ,the difference was statistically significant(P<0.05);the APACHEⅡ score ,mean lactic acid clearance rate and ScvO2 after 7 d treatment in the group A were significantly higher than those in the group B ,the difference was statistically significant (P<0.05) ,the survival rate within 3 months after admission in the group A was also significantly higher than that in the group B ,the difference was statistically significant (P<0.05) ,while the lactic acid concentration and ICU mechanical ventilation use rate after 7 d treatment in the group A were significantly lower than those in the group B with statistical difference (P<0.05).Conclusion The HMGB1 level change has a strong correlation with the prognosis ,the higher the HMGB1 level ,the worse the prognosis of patients with septic shock ,HMGB1 can be used as an important indicator of monitoring disease condition changes in sepsis ,which is worthy of attention in clinical laboratory.

Bioactive consistency evaluation of cardiotonic pill using marker genes / 药学学报

The study is aimed to develop a method in evaluation of the bioactive consistency of cardiotonic pill (CP). HepG2 cell line was employed as a biological detector. After treated with CP for 24 h, gene chip and qRT-PCR were used to select mRNAs that can represent the bioactivity of CP. Then similarity between different batches of CP were calculated based on expression levels of marker genes to evaluate the bioactive consistency of CP. Marker genes were selected according to the criteria as follows:① fold change 1.5; ② potential relevance to curative effects; ③ extensive involvement in the cellular functions and clustering analysis categories; ④ dose-dependent effect. A total of 10 genes were selected as bioactive markers of CP. Angular cosine was calculated to evaluate the similarity between two samples. The method was validated using intra-day precision and inter-day precision. Using angular cosine similarity, the intra-day and inter-day precision were 0.4% and 0.6%, respectively. The similarities of 6 batches of CDPs ranged from 0.992 to 0.999, and 1 batch of Compound Danshen Tablet was 0.534. The established method is specific and accurate, and provides comprehensive and objective evaluation of bioactive quality of CDPs. It can also benefit the bioactive consistency evaluation of other compounds in traditional Chinese medicines.

Role of p38MAPK signaling pathway in reduction of myocardial ischemia-reperfusion injury by morphine preconditioning in rats with chronic heart failure in vitro / 中华麻醉学杂志

Objective To investigate the role of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway in reduction of myocardial ischemia-reperfusion (I/R) injury by morphine preconditioning in the rats with chronic heart failure in vitro.Methods Adult male Sprague-Dawley rats,weighing 200-230 g,aged 6-7 weeks,in which doxorubicin 2 mg/kg was injected via the tail vein once a week for 6 consecutive weeks to induce chronic heart failure,were studied.At the end of 8th week,30 rats with chronic heart failure were randomly divided into 5 groups (n =6 each) using a random number table:sham operation group (group Sham),I/R group,morphine preconditioning group (group MPC),SB203580 (p38MAPK inhibitor) + morphine preconditioning group (group SBM),and SB203580 group (group SB).The hearts were quickly excised and passively perfused in a Langendorff apparatus and subjected to 30 min of occlusion of the anterior descending branch of the left coronary artery followed by 120 min of reperfusion to establish the model of myocardial I/R injury.After equilibration,the hearts were subjected to 3 cycles of 5 min perfusion with K-H solution containing morphine 1 μmol/L at 5-min intervals before ischemia in group MPC.In group SBM,the hearts were perfused with K-H solution containing SB203580 (5 μmol/L) for 45 min starting from l0 min before morphine preconditioning until 5 min of ischemia.In group SB,morphine preconditioning was not performed,and the hearts were only perfused with K-H solution containing SB203580 (5 μmol/L) starting from 40 min before ischemia until 5 min of ischemia.At 15 min of equilibration (baseline),5 and 10 min of reperfusion,the coronary effluent was collected to detect the activity of lactate dehydrogenase (LDH) using the chemical colorimetry.At 10 min of reperfusion,the expression of phosphor-p38MAPK (p-p38MAPK) in the myocardium was determined by Western blot in Sham,I/R and MPC groups.At 120 min of reperfusion,the area at risk (AAR),total areas of right and left ventricles (LV+RV),and infarct size (IS) were measured,and the IS/AAR ratio was calculated.Results Compared with group Sham,the LDH activity in coronary effluent during reperfusion and IS/AAR ratio were significantly increased in the other groups,and the expression of p-p38MAPK was significantly up-regulated in I/R and MPC groups (P＜0.05).Compared with group I/R,the LDH activity in coronary effluent during reperfusion was significantly decreased,the expression of p-p38MAPK was significantly up-regulated,and the IS and IS/AAR ratio were significantly decreased in group MPC (P＜0.05),and no significant change was found in the LDH activity in coronary effluent,IS and IS/AAR ratio in SBM and SB groups (P＞0.05).Compared with group MPC,the LDH activity in coronary effluent during reperfusion was significantly increased,and the IS and IS/AAR ratio were significantly increased in group SBM (P＜0.05).Conclusion The mechanism by which morphine preconditioning reduces myocardial I/R injury is related to activation of p38MAPK signaling pathway in the rats with chronic heart failure in vitro.

Research progress of the anti-tumor effect of matrine through some signaling pathways / 肿瘤研究与临床

Matrine is a traditional Chinese medicine extraction which can inhibit the proliferation, migration and apoptosis of tumor cells. Cell signal transduction affects the tumor biological behavior and growth condition. Except for the widely research of MAPK, JAK-STAT, NF-κB signal transduction pathways, the latest signaling pathways about matrine are Wnt/β-catenin signaling pathway and mTOR signaling pathway. These pathways are mainly activated by the phosphorylated key proteins to alleviate inflammatory reaction and inhibit the growth of tumor cells and tumor biological behaviors. The research of matrine by cell signaling pathways can provide molecular targeted therapy with theoretical basis. The relationship among different signaling pathways related to the anti-tumor effect of matrine is worth studying deeply in the future.

Effects of morphine preconditioning on expression of microRNAs during hypoxia-reoxygenation in H9 c2 myocardial cells / 中国药理学通报

Aim To evaluate the effects of morphine preconditioning ( MPC ) on the expression of microR-NAs ( miRNAs ) induced by hypoxia-reoxygenation (H/R) in H9c2 myocardial cells. Methods H9c2 cells were randomly divided into 3 groups ( n=4 each) as follows:control group ( CON) , hypoxia/ reoxygen-ation group ( H/R ) and morphine preconditioning group ( MPC+H/R) . The cells were cultured in nor-mal condition in CON group. The cells were subjected to 5 h hypoxia followed by 1 h reoxygenation in H/R group and MPC+H/R group. Specifically, the cells in MPC+H/R group were preconditioned with morphine with the final concentration of 1 μmol·L-1 for 10 min before H/R. After the treatment, CCK-8 was used to detect cell viability and chemical colorimetry was used to detect lactate dehydrogenase ( LDH ) activity in the culture medium. Cell apoptosis was assessed by An-nexin-V-FITC/PI flow cytometry. Relative expression of Fas protein was detected by Western blot. The ex-pression of miRNA in myocardial cells was analyzed by quantitative reverse transcription polymerase chain re-action ( qRT-PCR ) . Results Compared with CON group, the cell viability was significantly decreased, while the LDH activity, apoptotic rate and Fas protein expression were dramatically increased in group H/R (P<0. 01). However, MPC significantly increased the cell viability, whereas it decreased the LDH activity, apoptotic rate and Fas protein expression induced by H/R injury ( P < 0. 01 ) . The expressions of miR-133a-5p, miR-133b-5p, miR-664-1-5p, miR-6216 and let-7 e-5 p were markedly down-regulated by H/R as compared to CON group ( P <0. 05 ) , while MPC inhibited these miRNAs which were significantly down-regulated by H/R group ( P <0. 01 ) . Conclusion Morphine preconditioning might protect H9 c2 myocar-dial cells against H/R injury by regulating the expres-sion of miRNAs such as miR-133a-5p, miR-133b-5p, miR-664-1-5p, miR-6216 and let-7e-5p.

Study on the Optimization of Matrix Formula of Lanlian Ertong Qingre Cataplasm / 中国药房

OBJECTIVE:To optimize the matrix formula of Lanlian ertong qingre cataplasm. METHODS:Taking adhesion force,peel strength and sensory description as index,the ratio of matrix framework material(sodium polyacrylate-gan hydroxyl alu-minum-tartaric acid-glycerin) was optimized with orthogonal test. The single factor test was adopted to select adhesive and filler;the amount of penetrating agent azone was screened using the in vitro penetration amount of phillyrin. RESULTS:The best matrix ratio of Lanlian ertong qingre cataplasm was sodium polyacrylate-gan hydroxyl aluminum-tartaric acid-glycerin(4.0:0.8:0.4:15);PVP K-90 was used as adhesive,and bolus alba as filler;penetration enhancers azone accounted for 2.0%. Validation test showed, prepared cataplasm had good appearance,could stick on the 5th or the 6th ball;it's peel strength was 7.5 N;all RSDs of score were lower than 4%(n=3). CONCLUSIONS:The optimized matrix formula of Lanlian ertong qingre cataplasm is simple,stable and good in molding.