Phloretin ameliorates heart function after myocardial infarction via NLRP3/Caspase-1/IL-1ß signaling.

OBJECTIVES/AIMS: Inflammation is crucial in structural and electrical remodeling after myocardial infarction (MI), affecting cardiac pump function and conduction pathways. Phloretin possesses an anti-inflammation role by inhibiting the NLRP3/Caspase-1/IL-1ß pathway. However, the effects of Phloretin on cardiac contractile and electrical conduction function after MI remained unclear. Therefore, we aimed to investigate the potential role of Phloretin in a rat model of MI. METHODS: Rats were assigned into four groups: Sham, Sham+Phloretin, MI and MI+Phloretin, with ad libitum food and water. In the MI and MI+Phloretin groups, the left anterior descending coronary artery was occluded for 4 weeks, while the Sham and Sham+Phloretin groups received sham operation. The Sham+Phloretin group and the MI+Phloretin group received oral administration of Phloretin. In vitro, H9c2 cells were subjected to hypoxic conditions to simulate an MI model, with Phloretin for 24 h. Cardiac electrophysiological properties were assessed following MI, including the effective refractory period (ERP), action potential duration (APD)90 and ventricular fibrillation (VF) incidence. Echocardiography evaluated left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), left ventricular internal diameter at end-diastole (LVIDd), left ventricular internal diameter at end-systole (LVIDs), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) to assess cardiac function. Serum type B natriuretic peptide (BNP) level was applied to evaluate the degree of Heart failure (HF). The fibrosis area and severity were assessed by Masson staining and protein expression levels of collagen 3, collagen 1, TGF-ß and α-SMA. Western blot analysis estimated the protein expression levels of NLRP3, Pro Caspase-1, Caspase-1, ASC, IL-18, IL-1ß, pp38, p38, and Connexin43(Cx43) to elucidate the influence of inflammation on electrical remodeling after MI. RESULTS: Our findings demonstrate that Phloretin inhibits the NLRP3/Caspase-1/IL-1ß pathway, leading to the upregulation of Cx43 by limiting p38 phosphorylation, which further decreases susceptibility to ventricular arrhythmias (VAs). Additionally, Phloretin attenuated fibrosis by inhibiting inflammation to prevent HF. In vitro experiments also provided strong evidence supporting the inhibitory effects of Phloretin on the NLRP3/Caspase-1/IL-1ß pathway. CONCLUSION: Our results suggest that Phloretin could suppress the NLRP3/Caspase-1/IL-1ß pathway to reverse structural and electrical remodeling after MI to prevent the occurrence of VAs and HF.

Heterogeneously informed trading and the stock market efficiency during the COVID-19 pandemic.

This study investigates the U.S. stock market efficiency from the symmetric and asymmetric perspectives during the COVID-19 pandemic. We explore that the pandemic boosts (hurts) the information role of symmetrically (asymmetrically) informed trading. Specifically, we find that the epidemic outbreak and infection scale strengthen (weaken) the stock return reaction to symmetrically (asymmetrically) informed trading. Evidence also indicates that the effect of symmetrically (asymmetrically) informed trading on stocks' permanent price shocks and price informational efficiency is enhanced (impaired) during the pandemic. Moreover, all these effects are consistently more intensive to informed buys.

Propionate alleviated post-infarction cardiac dysfunction by macrophage polarization in a rat model.

BACKGROUND: The propionate (C3), the important components of short-chain fatty acids (SCFAs), had the effect of inhibiting pro-inflammatory macrophages. Earlier macrophages phenotypic transition from pro-inflammatory M1 to reparative M2 in early stage was a central juncture of cardiac dysfunction mitigation after myocardial infarction (MI). METHODS: 160 Sprague-Dawley rats were assigned to 4 groups: sham group (n = 40), sham + C3 group (n = 40), MI group (n = 40) and MI + C3 group (n = 40). The rats in sham + C3 and MI + C3 group were treated with oral sodium propionate (200 mM), and equivalent concentration of sodium chloride was administered in sham and MI group as control. After 7 days of propionate adaptive feeding, rats were anesthetized and induced the MI by coronary occlusion. The classification of macrophages, the level of inflammatory factors and inflammatory signaling were estimated at 3rd days after thoracotomy, and the extent of myocardial fibrosis was evaluated at 7th and 28th days after operation. Echocardiography was estimated on 28th day after surgery. RAW264.7 cells, stimulated by LPS + IFN-γ with or without propionate, were harvested for western blot and supernatants were collected for cytokine analysis by ELISA. RESULTS: Propionate administration reduced the MI-induced myocardial fibrosis in infarcted border and attenuated cardiac function deterioration compared with MI group. In comparison with MI group, propionate promoted macrophages reduction, macrophage M2-like polarization, and inflammatory cytokines decrease in infarcted border zone following MI, which partly depends on the inhibition of JNK/P38/NFκB signaling pathways. CONCLUSIONS: Oral propionate in early stage, as a nutritional intervention, alleviated post-MI chronic cardiac remodeling and cardiac dysfunction at least in part by modulating macrophages polarization and pro-inflammatory cytokine, which were associated with reduction of JNK/P38/NFκB phosphorylation.

The impact of COVID-19 on commodity options market: Evidence from China.

Considering the severe economic impact of COVID-19, this study examines COVID-19's influence on the Chinese commodity market. The literature shows that COVID-19's influence in China during its abatement period has not been well investigated. We address this issue by the intraday analysis of the volatility from 16 commodity options contracts in the Chinese commodity options market over the period 2019-2021. We demonstrate that while the pandemic eased in China after its initial outbreak, it still significantly affected the volatility of Chinese agricultural commodities options. In contrast, its impacts on the volatility of options for petrochemicals, ores, and metals are negligible. This pattern reflects the role of pandemic-led supply disruptions affecting agricultural commodity prices as necessities, contributing to higher price volatility relative to non-agricultural commodities, which are less volatile.

Complete genome sequence of a novel arlivirus from a yellow spotted stink bug (Erthesina fullo (Thunberg, 1783)).

Arlivirus is currently the only genus in the newly established viral family Lispiviridae. In this study, the complete genome sequence of a novel arlivirus, tentatively named "Nbu stink bug virus 1" (NbuSBV-1), was identified in an individual yellow spotted stink bug, Erthesina fullo (family Pentatomidae, order Hemiptera), which is a widely distributed phytophagous pest in Asia. NbuSBV-1 has a single negative-stranded RNA genome of 13,605 nucleotides in length, and it was predicted to contain six open reading frames (ORFs). Conserved domains of NbuSBV-1 were predicted in ORF1 (a nucleoprotein), ORF4 (a glycoprotein domain), ORF5 (a zinc-finger domain), and ORF6 (an RNA-directed RNA polymerase [RdRP] domain, an mRNA cap domain, and a methyltransferase domain). NbuSBV-1 shares 50.54% amino acid sequence identity in the RdRP region with its closest homolog, Lishì spider virus 2. In RdRP-based phylogenetic analysis, NbuSBV-1 was clearly clustered in a clade with other arliviruses. Furthermore, NbuSBV-1-derived small interfering RNAs (siRNAs) showed typical patterns of virus-derived siRNAs produced by the host antiviral RNA interference pathway. As far as we know, NbuSBV-1 is the first arlivirus identified in an insect of the family Pentatomidae.

The short-chain fatty acid propionate improved ventricular electrical remodeling in a rat model with myocardial infarction.

The short-chain fatty acid (SCFA) propionate (C3), a microorganism metabolite produced by gut microbial fermentation, has parasympathetic-activation effects. The cardiac autonomic rebalancing strategy is considered as an important therapeutic approach to myocardial infarction (MI)-produced ventricular arrhythmias (VAs). Thus, our research was designed to clarify the potential functions of the SCFA propionate in VAs and cardiac electrophysiology in MI rats. A hundred adult Sprague-Dawley rats were allocated to four groups: the sham group (200 mM sodium chloride), the sham + C3 group (200 mM propionate), the MI group (200 mM sodium chloride) and the MI + C3 group (200 mM propionate). In comparison with the sham group, propionate significantly increased the parasympathetic components heart rate variability (HRV) and acetylcholine levels, prolonged cardiac repolarization, induced STAT3 phosphorylation and up-regulated the c-fos expression in nodose ganglia and solitary nucleus. Propionate intake reduced the susceptibility to VAs. MI induced by coronary ligation caused a significant increase in the sympathetic components HRV, abnormal repolarization, global repolarization dispersion, norepinephrine and inflammatory cytokines, reduction and redistribution of Connexin 43 in the infarcted border zone, and activation of NFκB, which were attenuated in the MI + C3 group. Oral propionate supplementation, as a nutritional intervention, protected the heart against MI-induced VAs and cardiac electrophysiology instability partly by parasympathetic activation based on the gut-brain axis.

Complete genome sequence of a novel nege-like virus in aphids (genus Indomegoura).

BACKGROUND: Aphids are important vectors of numerous plant viruses. Besides plant viruses, a number of insect specific viruses (ISVs), such as nege/nege-like viruses, have been recently discovered in aphids of the genera Aphis, Rhopalosiphum, and Sitobion. FINDINGS: In this study, the complete genome sequence of a novel nege-like virus, tentatively named "Indomegoura nege-like virus 1" (INLV1), was identified in aphids of the genus Indomegoura. INLV1 possessed a single positive-stranded RNA genome with 8945 nucleotides, which was predicted to contain three typical open reading frames (ORFs) of negeviruses (including ORF1, ORF2, and ORF3), a 44-nt 5' untranslated region (UTR) and a 98-nt 3' UTR. Five conserved domains were predicted for INLV1, including an Alphavirus-like methyltransferase domain, a RNA virus helicase core domain, and a RNA-dependent RNA polymerase domain (RdRP) in ORF1, a DISB-ORF2_chro domain in ORF2, and a SP24 domain in ORF3. According to the maximum likelihood phylogenetic tree based on RdRP, INLV1 was grouped with barley aphid RNA virus 1 and Hubei virga-like virus 4, together with another two invertebrate viruses, which formed a distinct clade in the proposed group Centivirus. The alignment of RdRP domains for INLV1 and other nege/kita-like viruses suggested that RdRP of INLV1 contained the permuted C (GDD)- A [DX(4-5)D] -B [GX(2-3)TX(3)N] motifs, which were conserved in the Centivirus and Sandewavirus groups. Furthermore, the high abundance and typical characteristics of INLV1 derived small interfering RNAs clearly showed the active replication of INLV1 in the aphid Indomegoura. CONCLUSION: INLV1 is the first nege-like virus infecting aphids of the genus Indomegoura. As far as we know, it is also the first ISV revealed in this aphid genus.

One-step preparation of molybdenum disulfide/graphene nano-catalysts through a simple co-exfoliation method for high-performance electrocatalytic hydrogen evolution reaction.

HYPOTHESIS: Recently, molybdenum disulfide (MoS2) as a new type of catalyst, has been used for hydrogen evolution. In order to overcome the shortcomings of MoS2, such as poor conductivity and lack of catalytic activity sites, various materials were added to prepare composites, such as graphene with good conductivity. EXPERIMENTS: In this work, we combined MoS2 with graphene through a very simple liquid-phase salt-assisted co-exfoliation method. The obtained MoS2/graphene nano-composites have been further applied to electrocatalyst of hydrogen evolution reaction. The influences of different ratio of MoS2 to graphene and different solvents of exfoliation on the electrocatalytic activity for the hydrogen evolution reaction have been investigated in detail. FINDINGS: In general, the obtained MoS2/graphene nano-catalysts exhibits the smallest Tafel slope of 61 mV/dec with the exfoliation solvent of isopropanol, and 65 mV/dec in N-methyl pyrrolidone. All the MoS2/graphene composites exhibit much better catalytic activity than either MoS2 or graphene single substance due to the synergetic effect between MoS2 and graphene nanosheets.

Facile synthesis of a graphene/nickel-cobalt hydroxide ternary hydrogel for high-performance supercapacitors.

In this paper, a graphene/nickel-cobalt hydroxide ternary hydrogel (G-Ni-Co) with superior electrochemical performances was prepared by a simple hydrothermal method using Ni(NO3)2·6H2O, Co(NO3)2·6H2O, and graphene oxide as the starting materials. The mass fraction and the pH value of the reaction system were optimized. The prepared G-Ni-Co was assembled into a symmetric supercapacitor and its electrochemical performance was estimated. In a symmetric supercapacitor, the specific capacitance of G-Ni-Co is 551.3 F g-1 at the scan rate of 10 mV s-1 and 646.1 F g-1 at the current density of 0.5 A g-1, respectively. The specific capacitance still retains 70.8% after 5000 cycles at the scan rate of 100 mV s-1. The energy density reaches 108.6 W h kg-1 at a power density of 550.0 W kg-1 and remains 72.4 W h kg-1 at 7600.0 W kg-1, respectively.

Production of mono- to few-layer MoS2 nanosheets in isopropanol by a salt-assisted direct liquid-phase exfoliation method.

Here, we report a facile salt-assisted direct liquid-phase exfoliation method for mass production of MoS2 nanosheets. We choose organic solvent isopropanol (IPA) as exfoliation media and potassium ferrocyanide, potassium sodium tartrate, or sodium tartrate as salt, the assistant. The selected salts show universal and efficient assistant effect for the exfoliation of MoS2 in IPA. Especially, potassium ferrocyanide (K4Fe(CN)6) can enhance the exfoliation efficiency up to 73 times and a dispersion of MoS2 nanosheets with concentration as high as 0.240 mg mL-1 can be easily obtained in IPA-K4Fe(CN)6 system. Transmission electron microscopy, atomic force microscopy (AFM), and Raman spectroscopy show that bulk MoS2 has been successfully exfoliated into mono- to few-layer MoS2 nanosheets. AFM analysis indicates that nearly 60% flakes are monolayer in MoS2 dispersion.

The pristine graphene produced by liquid exfoliation of graphite in mixed solvent and its application to determination of dopamine.

The pristine graphene can be easily prepared in isopropanol-water mixture with salts as assistant via liquid-phase exfoliation method. The concentration of graphene dispersion reaches as high as 0.565 mg/mL. The graphene film prepared by drop-casting method shows an excellent electrical conductivity (7.095 × 104 S/m). Furthermore, an electrochemical biosensor based on the pristine graphene shows high selectivity and sensitivity for the determination of dopamine. The linear detection range for dopamine is 2.5-1500 µM with detection limit of 1.5 µM. This method provides a potential process for preparing high-quality graphene ready-to-use in low-boiling point solvent.

Mechanism underlying inhibition of inflammatory responses induced by α7nAChR agonist postcondi?tioning alone or in combination with remote limb ischemic postconditioning during myocardial I∕R in rats: the relationship with GSK?3β / 中华麻醉学杂志

Objective To evaluate the relationship between the mechanism underlying inhibition of inflammatory responses induced by α7 nicotinic acetylcholine receptor(α7nAChR)agonist postcondition?ing alone or in combination with remote limb ischemic postconditioning during myocardial ischemia?reperfu?sion(I∕R)and glycogen synthase kinase?3β(GSK?3β)in rats. Methods Eighty adult male Sprague?Dawley rats, aged 8 weeks, weighing 290-320 g, were divided into 4 groups(n=20 each)using a ran?dom number table: I∕R group, α7nAChR agonist postconditioning group(group P), remote limb ische?mic postconditioning group(group L)and α7nAChR agonist postconditioning plus remote limb ischemic postconditioning group(group P+L). Myocardial I∕R was induced by 30 min occlusion of the left anterior descending branch of coronary artery followed by 120 min reperfusion. Specific α7nAChR agonist PNU282987 2 mg∕kg was intravenously injected immediately before reperfusion in group P. In group L, limb ischemia was induced by tourniquet occlusion of bilateral hind paws for 10 min starting from 20 min of myocardial ischemia, and the tourniquet was released at the beginning of reperfusion. Combination of inter?vention measures previously described in P and L groups was performed in group P+L. Venous blood sam?ples were taken at 120 min of reperfusion for determination of serum troponin I(TnI)and creatine kinase?MB(CK?MB)concentrations, myocardial infarct size(IS)and expression of phosphorylated GSK?3β [p?GSK?3β(Ser536)], NF?κBp65 and phosphorylated nuclear factor?κBp65(p?NF?κBp65)in myocar?dial tissues(by Western blot). Results Compared with group I∕R, myocardial IS and serum cTnI and CK?MB concentrations were significantly decreased, the expression of p?GSK?3β(Ser9)in ischemic area was up?regulated, and the expression of p?NF?κBp65 in ischemic area was down?regulated in P, L and P+L groups(P<0.05). Compared with group L, myocardial IS and serum cTnI and CK?MB concentrations were significantly decreased, the expression of p?GSK?3β(Ser9)in ischemic area was up?regulated, and the expression of p?NF?κBp65 in ischemic area was down?regulated in group P+L(P<0.05). Conclusion The mechanism by which α7nAChR agonist postconditioning alone or in combination with remote limb is?chemic postconditioning inhibits inflammatory responses during myocardial I∕R may be related to inhibiting GSK?3β activity in rats.

Effect of Autophagy Inhibition on the Protection of Ischemia Preconditioning against Myocardial Ischemia/Reperfusion Injury in Diabetic Rats / 中华医学杂志(英文版)

<p><b>Background</b>Ischemia preconditioning (IPC) remains the most powerful intervention of protection against myocardial ischemia/reperfusion injury (IRI), but diabetes can weaken or eliminate its cardioprotective effect and detailed mechanisms remain unclear. In this study, we aimed to explore whether changes of autophagy in the diabetic condition are attributable to the decreased cardioprotective effect of IPC.</p><p><b>Methods</b>Sixty diabetic male Sprague-Dawley rats were randomly divided into the control (C), IRI, rapamycin (R), wortmannin (W), rapamycin + IPC (R + IPC), and wortmannin + IPC (W + IPC) groups. The in vivo rat model of myocardial IRI was established by ligaturing and opening the left anterior descending coronary artery via the left thoracotomy. Durations of ischemia and reperfusion are 30 min and 120 min, respectively. Blood samples were taken at 120 min of reperfusion for measuring serum concentrations of troponin I (TnI) and creatine kinase isoenzyme MB (CK-MB) using the enzyme-linked immunosorbent assay. The infarct size was assessed by Evans blue and triphenyltetrazolium chloride staining. The expressions of LC3-II, beclin-1, phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and P-Akt/Akt ratio in the ischemic myocardium were assessed by Western blotting.</p><p><b>Results</b>Compared to the IRI group, infarct size (56.1% ± 6.1% vs. 75.4 ± 7.1%, P < 0.05), serum cTnI (0.61 ± 0.21 vs. 0.95 ± 0.26 ng/ml, P < 0.05), and CK-MB levels (6.70 ± 1.25 vs. 11.51 ± 2.35 ng/ml, P < 0.05) obviously decreased in the W + IPC group. Compared with the C group, myocardial expressions of LC3-II (0.46 ± 0.04 and 0.56 ± 0.04 vs. 0.36 ± 0.04, P < 0.05) and beclin-1 (0.34 ± 0.08 and 0.38 ± 0.07 vs. 0.24 ± 0.03, P < 0.05) evidently increased, and myocardial expressions of mTOR (0.26 ± 0.08 and 0.25 ± 0.07 vs. 0.38 ± 0.06, P < 0.05), PI3K (0.29 ± 0.04 and 0.30 ± 0.03 vs. 0.38 ± 0.02, P < 0.05), and P-Akt/Akt ratio (0.49 ± 0.10 and 0.48 ± 0.06 vs. 0.72 ± 0.07, P < 0.05) markedly decreased in the IRI and R groups, indicating an increased autophagy. Compared with the IRI group, myocardial expression of beclin-1 (0.26 ± 0.03 vs. 0.34 ± 0.08, P < 0.05) significantly decreased, and myocardial expressions of mTOR (0.36 ± 0.04 vs. 0.26 ± 0.08, P < 0.05), PI3K (0.37 ± 0.03 vs. 0.29 ± 0.04, P < 0.05), and P-Akt/Akt ratio (0.68 ± 0.05 vs. 0.49 ± 0.10, P < 0.05) increased obviously in the W + IPC group, indicating a decreased autophagy.</p><p><b>Conclusions</b>Increased autophagy in the diabetic myocardium is attributable to decreased cardioprotection of IPC, and autophagy inhibited by activating the PI3K-Akt-mTOR signaling pathway can result in an improved protection of IPC against diabetic myocardial IRI.</p>

Feasibility Analysis of Oxygen-Glucose Deprivation-Nutrition Resumption on H9c2 Cells Models of Myocardial Ischemia-Reperfusion Injury / 中华医学杂志(英文版)

<p><b>Background</b>Oxygen-glucose deprivation-nutrition resumption (OGD-NR) models on H9c2 cells are commonly used in vitro models of simulated myocardial ischemia-reperfusion injury (MIRI), but no study has assessed whether these methods for establishing in vitro models can effectively imitate the characteristics of MIRI in vivo. This experiment was designed to analyze the feasibility of six OGD-NR models of MIRI.</p><p><b>Methods</b>By searching the PubMed database using the keywords "myocardial reperfusion injury H9c2 cells," we obtained six commonly used OGD-NR in vitro models of MIRI performed on H9c2 cells from more than 400 published papers before January 30, 2017. For each model, control (C), simulated ischemia (SI), and simulated ischemia-reperfusion (SIR) groups were assigned, and cell morphology, lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) levels, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory cytokines were examined to evaluate the characteristics of cell injury. Subsequently, a coculture system of cardiomyocyte-endothelial-macrophage was constructed. The coculture system was dealt with SI and SIR treatments to test the effect on cardiomyocytes survival.</p><p><b>Results</b>For models 1, 2, 3, 4, 5, and 6, SI treatment caused morphological damage to cells, and subsequent SIR treatment did not cause further morphological damage. In the models 1, 2, 3, 4, 5 and 6, LDH release was significantly higher in the SI groups than that in the C group (P < 0.05), and was significantly lower in the SIR groups than that in the SI groups (P < 0.05), except for no significant differences in the LDH release between C, SI and SIR groups in model 6 receiving a 3-h SI treatment. In models 1, 2, 3, 4, 5, and 6, compared with the C group, ATP levels of the SI groups significantly decreased (P < 0.05), ROS levels increased (P < 0.05), and MMP levels decreased (P < 0.05). Compared with the SI group, ATP level of the SIR groups was significantly increased (P < 0.05), and there was no significant ROS production, MMP collapse, and over inflammatory response in the SIR groups. In a coculture system of H9c2 cells-endothelial cells-macrophages, the proportion of viable H9c2 cells in the SIR groups was not reduced compared with the SI groups.</p><p><b>Conclusion</b>All the six OGD-NR models on H9c2 cells in this experiment can not imitate the characteristics of MIRI in vivo and are not suitable for MIRI-related study.</p>

Relationship between autophagy and diabetes mellitus-caused influence on ischemic preconditioning-induced cardioprotection in rats / 中华麻醉学杂志

Objective To evaluate the relationship between autophagy and diabetes mellitus-caused influence on ischemic preconditioning ( IP )-induced cardioprotection in rats. Methods Clean-grade healthy male Sprague-Dawley rats, aged 12 weeks, weighing 290-320 g, were used in this study. Diabe-tes mellitus was induced by high-fat and high-sucrose diet ( lasting for 1 week) and intraperitoneal streptozo-tocin 50 mg∕kg ( for 2 consecutive days) and confirmed by fasting blood glucose level≥16. 65 mmol∕L ( for 1 week) . Thirty rats with diabetes mellitus, weighing 350-450 g, were divided into 3 groups ( n=10 each) using a random number table method: sham operation group ( DM-S group) , myocardial ischemia-reperfusion ( I∕R) group ( DM-IR group) and IP group ( DM-IP group) . Another 30 non-diabetic rats were selected and divided into 3 groups ( n=10 each ) using a random number table method: sham operation group (S group), myocardial I∕R group (IR group) and IP group. Myocardial ischemia was induced by ligation of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion. IP was produced by 3 cycles of 5-min ischemia followed by 5-min reperfusion prior to establishment of myo-cardial I∕R injury model in IP and DM-IP groups. Blood samples were collected from the internal jugular vein at the end of reperfusion for measuring serum concentrations of cardiac troponin I ( cTnI) and creatine kinase-MB ( CK-MB) . The rats were then sacrificed and myocardial tissues were obtained for determination of myocardial infarct size and expression of microtubule-associated protein 1 light chain 3 Ⅱ ( LC3 Ⅱ) , Beclin-1, phosphatidyl-inositol 3-kinase (PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt) and mammalian target of rapamycin ( mTOR) ( by Western blot) . p-Akt∕Akt ratio was calculated. Results Compared with S group, the serum cTnI and CK-MB concentrations were significantly increased, the percentage of myocardial infarct size was increased, the expression of LC3Ⅱand Beclin-1 in myocardial tis-sues was up-regulated, the expression of PI3K and mTOR was down-regulated, and p-Akt∕Akt ratio was decreased in IR group (P<0. 05). Compared with IR group, the serum cTnI and CK-MB concentrations were significantly decreased, the percentage of myocardial infarct size was decreased, the expression of LC3Ⅱand Beclin-1 in myocardial tissues was down-regulated, the expression of PI3K and mTOR was up-regulated, and p-Akt∕Akt ratio was increased in IP group ( P<0. 05) . Compared with DM-S group, the se-rum cTnI and CK-MB concentrations were significantly increased, the percentage of myocardial infarct size was increased, the expression of LC3Ⅱ and Beclin-1 in myocardial tissues was up-regulated, the expres-sion of PI3K and mTOR was down-regulated, and p-Akt∕Akt ratio was decreased in DM-IR group ( P<0. 05) . There was no significant difference in the parameters mentioned above between DM-IP group and DM-IR group (P>0. 05). Conclusion The mechanism by which diabetes mellitus abolishes IP-induced cardioprotection may be related to inhibiting activation of PI3K-Akt-mTOR signaling pathway and enhanced autophagy in rats.

Role of PI3K/Akt or JAK/STAT-3 signaling pathways in reduction of myocardial ischemia-reperfusion injury by combination of limb ischemic and morphine postconditioning in rats / 中华麻醉学杂志

Objective To evaluate the role of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)or Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT-3)signaling pathways in reduction of myocardial ischemia-reperfusion(I/R)injury by combination of limb ischemic and morphine postconditioning in rats.Methods Eighty SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 280-320 g,were used in the study.Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.The rats were divided into 8 groups(n=10 each)using a random number table:I/R group,limb ischemic postconditioning group(LIP group),morphine postconditioning group(group MP),combination of limb ischemic and morphine postconditioning group(LIP+MP group)and signaling pathway blocker groups(I/Rb group,LIPb group,MPb group,LIP+MPb group).In I/R,LIP,MP and LIP+MP groups,the animals were sacrificed at the end of reperfusion,and myocardial specimens in ischemic and non-ischemic regions were obtained for determination of phosphorylated STAT-3(p-STAT-3),STAT-3,phosphorylated Akt(p-Akt)and Akt expression(by Western blot)and STAT-3 and Akt mRNA expression(by polymerase chain reaction).In I/Rb,LIPb,MPb and LIP+MPb groups,PI3K/Akt signaling pathway blocker LY294002 0.3 mg/kg was intravenously injected in 5 rats of each group,and JAK/STAT-3 signaling pathway blocker AG490 5 mg/kg was intravenously injected in the other 5 rats of each group.The animals were sacrificed at the end of reperfusion,and myocardial specimens in the ischemic region were obtained for determination of myocardial infarct size.Results Compared with I/R group,the p-STAT-3/STAT-3 ratio in LIP,MP and LIP+MP groups and p-Akt/Akt ratio in LIP+MP group were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P0.05).When JAK2 inhibitor AG490 was applied,the myocardial infarct size was significantly smaller in LIP+MPb group than in I/Rb,LIPb and MPb groups(P0.05).Conclusion Combination of limb ischemic and morphine postconditioning can enhance the activation of PI3K/Akt or JAK/STAT-3 signaling pathways,and the cardioprotection is dependent on the integrity of the PI3K/Akt signaling pathway and partially dependent on the integrity of the JAK/STAT-3 signaling pathway when applied in combination in rats.

ISMAC: An Intelligent System for Customized Clinical Case Management and Analysis.

Clinical cases are primary and vital evidence for Traditional Chinese Medicine (TCM) clinical research. A great deal of medical knowledge is hidden in the clinical cases of the highly experienced TCM practitioner. With a deep Chinese culture background and years of clinical experience, an experienced TCM specialist usually has his or her unique clinical pattern and diagnosis idea. Preserving huge clinical cases of experienced TCM practitioners as well as exploring the inherent knowledge is then an important but arduous task. The novel system ISMAC (Intelligent System for Management and Analysis of Clinical Cases in TCM) is designed and implemented for customized management and intelligent analysis of TCM clinical data. Customized templates with standard and expert-standard symptoms, diseases, syndromes, and Chinese Medince Formula (CMF) are constructed in ISMAC, according to the clinical diagnosis and treatment characteristic of each TCM specialist. With these templates, clinical cases are archived in order to maintain their original characteristics. Varying data analysis and mining methods, grouped as Basic Analysis, Association Rule, Feature Reduction, Cluster, Pattern Classification, and Pattern Prediction, are implemented in the system. With a flexible dataset retrieval mechanism, ISMAC is a powerful and convenient system for clinical case analysis and clinical knowledge discovery.

Ischemic preconditioning produces more powerful anti-inflammatory and cardioprotective effects than limb remote ischemic postconditioning in rats with myocardial ischemia-reperfusion injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Both ischemic preconditioning (IPC) and limb remote ischemic postconditioning (LRIPOC) have been shown to possess significantly different cardioprotective effects against the myocardial ischemia reperfusion injury (IRI), but no study has compared the anti-inflammatory effects of IPC and LRIPOC during myocardial IRI process. We hypothesized that IPC and LRIPOC would produce different anti-inflammatory effects in an in vivo rat model with myocardial IRI.</p><p><b>METHODS</b>Eighty rats were randomly allocated into four equal groups: sham group, IRI group, IPC group and LRIPOC group. In 10 rats randomly selected from each group, serum levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 were assessed, and infarct size was determined. In another 10 rats of each group, myocardial levels of TNF-α, HMGB1, ICAM1, IL-1, IL-6 and IL-10 in both ischemic and non-ischemic regions were measured.</p><p><b>RESULTS</b>The infarct size was significantly lower in IPC and LRIPOC groups than in IRI group. The serum and myocardial levels of pro-inflammatory cytokines including TNF-α, HMGB1, ICAM1, IL-1 and IL-6 during reperfusion were significantly reduced in IPC and LRIPOC groups compared to IRI group. As compared to the IPC group, infarct size, serum level of TNF-α at 60 minutes of reperfusion, serum levels of HMGB1 and ICAM1 at 120 minutes of reperfusion, myocardial levels of TNF-α, ICAM1, IL-1 and IL-6 in the ischemic region, myocardial levels of ICAM1, IL-1 and IL-6 in the non-ischemic region were significantly increased in the LRIPOC group.</p><p><b>CONCLUSIONS</b>In the rats with myocardial IRI, IPC produces more powerful inhibitory effects on local myocardial and systemic inflammatory responses than LRIPOC. This may be partly attributed to more potent cardioprotection produced by IPC.</p>

[Research on the mercury species in Jiaozhou Bay in spring].

In April 2010, seawater samples collected every twenty minutes in the Jiaozhou Bay were separated and determined in-situ and indoor to study mercury speciation and its daily variation and to further understand the end-result and effect of mercury on offshore environment. Results showed that dissolved element mercury (DEM) concentration of seawater ranged from 38.2 pg x L(-1) to 156 pg x L(-1), with an average value of 97.5 pg x L(-1). The highest and the lowest value appeared at around 13:00 and 17:30 respectively under the influence of tide and light intensity. DEM concentration gradually declined with depth. DEM of surface sea primarily derived from photoreduction of bivalent mercury. Dissolved mercury (DHg) concentrations ranged from 7.32 ng x L(-1) to 49.1 ng x L(-1) (average value was 13.9 ng x L(-1)), from 4.39 ng x L(-1) to 19.3 ng x L(-1) (average value was 7.94 ng x L(-1)) for dissolved reactive mercury (RHg). The maximum peaks of DHg and RHg all appeared around 13:00, due to dirty seawater carried by tidal movement in the lowest tide. The variation trend with depth of RHg and DHg concentrations was similar at different time. Under the influence of the light and water temperature, the ratio of RHg to DHg was higher in the surface water. RHg accounted for 62% of DHg, so the mercury had relatively high activity and biological availability, and contributed to the form of DEM. The methylmercury concentration was low, with an average value of 0.30 ng x L(-1), and some samples were lower than the detection limit.

Combined postconditioning with ischemia and α7nAChR agonist produces an enhanced protection against rat myocardial ischemia reperfusion injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Inflammation is one of important mechanisms for myocardial ischemia reperfusion injury (IRI). Ischemia postconditioning (IPOC) can protect the heart against IRI by inhibiting inflammation, but its cardioprotection is weaker than that of ischemia preconditioning. Recently, the α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR) agonist has shown anti-inflammatory effects in many diseases related to inflammation. This randomized controlled experiment was designed to evaluate whether combined postconditioning with IPOC and the α7nAChR agonist could produce an enhanced cardioprotection in a rat in vivo model of acute myocardial IRI.</p><p><b>METHODS</b>Fifty Sprague-Dawley rats were randomly divided into five equal groups: sham group, control group, IPOC group, α7nAChR agonist postconditioning group (APOC group) and combined postconditioning with IPOC and α7nAChR agonist group (combined group). Hemodynamic parameters were recorded during the periods of ischemia and reperfusion. Serum concentrations of troponin I (TnI), tumor necrosis factor α (TNF-α) and high-mobility group box 1 (HMGB-1) at 180 minutes after reperfusion were assayed in all groups. At the end of the experiment, the infarct size was assessed from excised hearts by Evans blue and triphenyl tetrazolium chloride staining.</p><p><b>RESULTS</b>As compared to the sham group, the infarct size in the other four groups was significantly increased, serum levels of TnI, TNF-α and HMGB1 in the control group and TNF-α, HMGB1 in the IPOC group were significantly increased. The infarct size and serum concentrations of TNF-α, HMGB1 and TnI in the IPOC, APOC and combined groups were significantly lower than those in the control group. As compared to the IPOC group, the infarct size in the combined group was significantly decreased, serum concentrations of TnI, TNF-α and HMGB1 in the APOC and combined groups were significantly reduced. Although the infarct size was significantly smaller in the combined group than in the APOC group, serum levels of TNF-α and HMGB1 were significantly higher in the combined group than in the APOC group.</p><p><b>CONCLUSIONS</b>In a rat in vivo model of acute myocardial IRI, combined postconditioning with IPOC and the α7nAChR agonist can produce enhanced protection against myocardial IRI by increasing the anti-inflammatory effect.</p>