Multi-targeted therapeutic effects of Sankudiwan (SKDW) in myocardial ischemia-reperfusion injury: a comprehensive study.

OBJECTIVE: This study aimed to investigate the therapeutic effects and underlying mechanisms of Sankudiwan (SKDW) on myocardial ischemia-reperfusion injury (MIRI) in a rat model. MATERIALS AND METHODS: Rats were subjected to MIRI and treated with varying doses of SKDW. The myocardial infarct size, cardiac function, histological changes, apoptosis, and inflammation were assessed using TTC staining, echocardiography, Hematoxylin and Eosin (HE) staining, TUNEL staining, and ELISA assays. We further explored SKDW's influence on cardiomyocyte mitochondria and inflammatory factor expression. Moreover, oxidative stress-related parameters and differentially expressed genes were analyzed using bioinformatics approaches. RESULTS: SKDW significantly reduced myocardial infarct size and improved cardiac function, demonstrating a dose-dependent therapeutic potential. It ameliorated myocardial tissue damage at the histological level, inhibited cardiomyocyte apoptosis, and mitigated inflammatory response. SKDW also enhanced mitochondrial energy metabolism and suppressed the levels of oxidative stress markers. Bioinformatics analysis identified key differentially expressed genes (DEGs), including cbln1, Tgm1, Trh, and Ccl27, possibly mediating the therapeutic effects of SKDW. CONCLUSIONS: SKDW exerts its therapeutic effects on MIRI through the modulation of several genes and pathways related to inflammation, apoptosis, mitochondrial function, and oxidative stress. Our findings provide a scientific basis for the clinical application of SKDW in the treatment of MIRI.

Calcium (Ca2+ ) sensors and MYC2 are crucial players during jasmonates-mediated abiotic stress tolerance in plants.

Plants evolve stress-specific responses that sense changes in their external environmental conditions and develop various mechanisms for acclimatization and survival. Calcium (Ca2+ ) is an essential stress-sensing secondary messenger in plants. Ca2+ sensors, including calcium-dependent protein kinases (CDPKs), calmodulins (CaMs), CaM-like proteins (CMLs), and calcineurin B-like proteins (CBLs), are involved in jasmonates (JAs) signalling and biosynthesis. Moreover, JAs are phospholipid-derived phytohormones that control plant response to abiotic stresses. The JAs signalling pathway affects hormone-receptor gene transcription by binding to the basic helix-loop-helix (bHLH) transcription factor. MYC2 acts as a master regulator of JAs signalling module assimilated through various genes. The Ca2+ sensor CML regulates MYC2 and is involved in a distinct mechanism mediating JAs signalling during abiotic stresses. This review highlights the pivotal role of the Ca2+ sensors in JAs biosynthesis and MYC2-mediated JAs signalling during abiotic stresses in plants.

Potential cerebrovascular protective functions of lycium barbarum polysaccharide in alleviating hyperglycemia-aggravated cerebral ischemia/reperfusion injury in hyperglycemic rats.

OBJECTIVE: Lycium barbarum polysaccharide (LBP) is the efficient primary compound of Lycium barbarum and has been shown to alleviate hyperglycemia-aggravated cerebral ischemia/reperfusion (I/R) injury. However, the cerebrovascular changes related to diabetes mellitus (DM) and the potential cerebrovascular protective effects of LBP are still unknown. This study aimed to explore the cerebrovascular protective functions of LBP on cerebral I/R injury in diabetic rats and its potential mechanisms. MATERIALS AND METHODS: Sprague Dawley (SD) rats were separated into three groups: the normoglycemic (NG), diabetic hyperglycemic (HG), and HG + LBP (50 mg/kg) treatment groups. A 30 min transient middle cerebral artery occlusion (tMCAO) with 24 h reperfusion was established. The neurological deficits, cerebral water content, infarct volume, and cerebrovascular permeability were assessed to evaluate the extent of cerebral injury. Histopathological alterations were assessed by hematoxylin and eosin, Nissl, immunohistochemical, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. A transmission electron microscope was used to detect ultrastructural alterations, and a western blot was used to examine protein expression. RESULTS: The HG rats exhibited a significant increase in neurological deficits, cerebral water content, infarct volume, cerebrovascular permeability, neural cell death, and apoptosis compared with the NG rats, and the LBP treatment alleviated these effects. Cerebrovascular structure analysis showed that the cross-sectional area (CSA) and wall thickness were remarkably altered in the HG rats compared with the NG rats. The LBP treatment protected the cerebrovascular structure and vasoreactivity by decreasing the wall thickness and increasing the CSA, α-smooth muscle actin, and endothelial nitric oxide synthase expression of cerebral vessels. CONCLUSIONS: The intake of LBP benefits the cerebrovascular structure and vasoreactivity in diabetic rats. Our research provides a possible new strategy for treating stroke in patients with DM.

V-ATPase subunit a is required for survival and midgut development of Locusta migratoria.

The vacuolar-type H+ -ATPase (V-ATPase) is an ATP-dependent proton pump, which regulates various cellular processes. To date, most functional studies on V-ATPases of insects have focused on subunits of the V1 complex, and there is little information on the VO genes. In this study, two cDNA sequences of LmV-ATPase a were identified in Locusta migratoria. RT-qPCR analysis revealed that LmV-ATPase a1 and LmV-ATPase a2 are differentially expressed in various tissues and developmental stages. Injection of dsRNA for the common region of LmV-ATPase a1 and LmV-ATPase a2 into third-instar nymphs resulted in a significant suppression of LmV-ATPase a. The injected nymphs ceased feeding, lost body weight and finally died at a mortality of 98.6%. Furthermore, aberrations of midgut epithelial cells, the accumulation of electron-lucent vesicles in the cytoplasm, and a partially damaged brush border were observed in dsLmV-ATPase a-injected nymphs using transmission electron microscopy. Especially, the mRNA level of wingles, and notch genes were dramatically down-regulated in the dsLmV-ATPase a-injected nymphs. Taken together, our results suggest that LmV-ATPase a is required for survival and midgut development of L. migratoria. Hence, this gene could be a good target for RNAi-based control against locusts.

Optical lattice vibrations in monolayer hexagonal boron nitride from macroscopic equations.

Using two pairs of macroscopic equations deduced from a dipole lattice model including electronic polarization (EP) of ions and local field effects (LFEs) self-consistently, optical lattice vibrations in monolayer hexagonal boron nitride (BN) are studied theoretically for both in-plane and out-of-plane motions. Longitudinal and transverse optical (LO and TO) modes and out-of-plane (ZO) modes are derived, and explicit expressions are obtained for phonon dispersion, group velocity and density of states. The analytical phonon dispersion relations describe previous numerical results very well; the LO phonon dispersion is identical to the analytical expression of Sohier et al, which shows the degeneracy of the LO and TO modes at [Formula: see text] and the splitting at finite wavevectors due to the long-range macroscopic field. Whilst relating to microscopic quantities, the linear coefficients of the lattice equations are determined by first-principles calculated quantities (such as macroscopic susceptibilities). Therefore the EP and LFEs on the vibrational properties are studied. With no EP or LFEs, all the phonon frequencies are overestimated significantly. Including EP, the LFEs increase (decrease) the in-plane (out-of-plane) dielectric susceptibility by a factor of 2.5-3.5. Both ionic EP and LFEs should be included to obtain an accurate description of the lattice dynamics.

Osteoprotegerin mediate RANK/RANKL signaling inhibition eases asthma inflammatory reaction by affecting the survival and function of dendritic cells

Introduction: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Dendritic cells (DCs) are considered the most important antigen-presenting cell in asthma airway inflammatory reaction. But whether osteoprotegerin (OPG) mediate RANK/RANKL signaling inhibition influences asthma development by affecting the survival and function of DCs remains unclear. In this study, we assessed the effects of OPG on DCs and asthma. Material and methods: BALB/c mice immunized with ovalbumin (OVA) were challenged thrice with an aerosol of OVA every second day for eight days. Dexamethasone (1.0mg/kg) or OPG (50 mig/kg) was administered intraperitoneally to OVA-immunized BALB/c mice on day 24 once a day for nine days. Mice were analyzed for effects of OPG on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. The expression of RANK and β-actin was detected by Western Blot. DCs were isolated from mouse bone morrow. Cell survival was assessed by cell counting. The content of IL-12 was detected by ELISA. Results: Results showed that OVA increased the number of inflammatory factors in BALF, elevated lung inflammation scores in mice. OPG reversed the alterations induced by OVA in the asthmatic mice. OPG inhibited the survival and function of DC via inhibition of RANK/RANKL signaling. Conclusions: This research proved inhibition of RANK/RANKL signaling by OPG could ease the inflammatory reaction in asthma, providing new evidence for the application of OPG on asthma

No disponible

Nuclear receptor hormone receptor 39 is required for locust moulting by regulating the chitinase and carboxypeptidase genes.

The nuclear receptor-mediated 20-hydroxyecdysone (20E) signalling pathway plays crucial roles in insects by initiating and regulating moulting and metamorphosis. In the present study, we identified and characterized a cDNA encoding a putative nuclear receptor protein (Locusta migratoria hormone receptor 39, LmHR39) based on L. migratoria transcriptomics data. Reverse-transcription quantitative PCR (RT-qPCR) revealed that LmHR39 shows low-level expression in the early days of fifth-instar nymphs, and peak expression occurs on day 5, which is followed by a decrease before ecdysis. LmHR39 transcription could be induced by 20E in vivo and was significantly suppressed by knocking down the expression of the L. migratoria ecdysone receptor gene and early-late gene LmHR3. After RNA interference of LmHR39 with double-stranded RNA (dsRNA), 85% of the insects showed abnormal morphology, with curly wings after moulting and delayed eclosion time. Haematoxylin and eosin staining indicated that apolysis of the integument and wing pad cuticle in the dsLmHR39-treated insects was delayed compared to that in the dsRNA for green fluorescent protein-injected control. Furthermore, RNA-sequencing and RT-qPCR analysis showed the expression level of carboxypeptidase genes (Carboxypeptidase A (CPA) and Carboxypeptidase M (CPM)) and chitin degrading genes (LmChitinase5 (LmCHT5) and LmChitinase10 (LmCHT10)) dramatically declined in the dsLmHR39-treated insects, implying that the LmHR39-mediated 20E signalling pathway is involved in the regulation of carboxypeptidase genes (CPA and CPM) and chitinase genes (LmCHT5 and LmCHT10), and participated in apolysis of the integument and wing pads during locust moulting.

Two-dimensional excitons in monolayer transition metal dichalcogenides from radial equation and variational calculations.

Exciton energy spectra of monolayer transition metal dichalcogenides (TMDs) in various dielectric environments are studied with an effective mass model using the Keldysh potential for the screened electron-hole interaction. Two-dimensional (2D) excitons are calculated by solving a radial equation (RE) with a shooting method, using boundary conditions that are derived by applying the asymptotic properties of the Keldysh potential. For any given main quantum number n, the exciton Bohr orbit shrinks as [Formula: see text] becomes larger (m is the orbital quantum number) resulting in increased strength of the electron-hole interaction and a decrease of the exciton energy. Further, both the exciton energy and its effective radius decrease linearly with [Formula: see text]. The screened hydrogen model (SHM) (Olsen et al 2016 Phys. Rev. Lett. 116 056401) is examined by comparing its exciton energy spectra with our RE solutions. While the SHM is found to describe the nonhydrogenic exciton Rydberg series (i.e. the energy's dependence on n) reasonably well, it fails to account for the linear dependence of the exciton energy on the orbital quantum number. The exciton effective radius expression of the SHM can characterize the exciton radius's dependence on n, but it cannot properly describe the exciton radius's dependence on m, which is the cause of the SHM's poor description of the exciton energy's m-dependence. Analytical variational wave-functions are constructed with the 2D hydrogenic wave-functions for a number of strongly bound exciton states, and very close exciton energies and wave-functions are obtained with the variational method and the RE solution (exciton energies are within a 6% of deviation). The variational wave-functions are further applied to study the Stark effects in 2D TMDs, with an analytical expression derived for evaluating the redshift the ground state energy.

Osteoprotegerin mediate RANK/RANKL signaling inhibition eases asthma inflammatory reaction by affecting the survival and function of dendritic cells.

INTRODUCTION: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Dendritic cells (DCs) are considered the most important antigen-presenting cell in asthma airway inflammatory reaction. But whether osteoprotegerin (OPG) mediate RANK/RANKL signaling inhibition influences asthma development by affecting the survival and function of DCs remains unclear. In this study, we assessed the effects of OPG on DCs and asthma. MATERIAL AND METHODS: BALB/c mice immunized with ovalbumin (OVA) were challenged thrice with an aerosol of OVA every second day for eight days. Dexamethasone (1.0mg/kg) or OPG (50µg/kg) was administered intraperitoneally to OVA-immunized BALB/c mice on day 24 once a day for nine days. Mice were analyzed for effects of OPG on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. The expression of RANK and ß-actin was detected by Western Blot. DCs were isolated from mouse bone morrow. Cell survival was assessed by cell counting. The content of IL-12 was detected by ELISA. RESULTS: Results showed that OVA increased the number of inflammatory factors in BALF, elevated lung inflammation scores in mice. OPG reversed the alterations induced by OVA in the asthmatic mice. OPG inhibited the survival and function of DC via inhibition of RANK/RANKL signaling. CONCLUSIONS: This research proved inhibition of RANK/RANKL signaling by OPG could ease the inflammatory reaction in asthma, providing new evidence for the application of OPG on asthma.

LmCDA1 organizes the cuticle by chitin deacetylation in Locusta migratoria.

Cells produce an extracellular matrix (ECM) with a stereotypic organization that is important for tissue function. The insect cuticle is a layered ECM that mainly consists of the polysaccharide chitin and associated proteins adopting a quasi-crystalline structure. Our understanding of the molecular mechanisms deployed during construction of the highly ordered protein-chitin ECM so far is limited. In this study, we report on the role of the chitin deacetylase 1 (LmCDA1) in the organization of the protein-chitin ECM in the migratory locust Locusta migratoria, and LmCDA1 localizes predominantly to the apical tier of the protein-chitin ECM, but it is also found in lower regions. Reduction of LmCDA1 function correlates with lower amounts of chitin and impedes conversion of chitin to chitosan by deacetylation. Establishment of the quasi-crystalline architecture of the protein-chitin ECM is, however, independent of LmCDA1 activity, but it is dependent on another chitin deacetylase, LmCDA2, which has no detectable effects on chitin deacetylation and, as shown previously, no influence on chitin content. Our data reveal that LmCDA1 and LmCDA2 act in parallel and independently from each other in defining the dimensions of the cuticle. Both enzymes are non-uniformly distributed within the protein-chitin matrix, suggesting a site-autonomous function.

Influences of remifentanil on myocardial ischemia-reperfusion injury and the expressions of Bax and Bcl-2 in rats.

OBJECTIVE: To investigate the influences of remifentanil on myocardial ischemia-reperfusion injury in rats and the expressions of b-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and other apoptosis-related proteins. MATERIALS AND METHODS: A total of 60 Sprague-Dawley (SD) rats were randomly divided into sham operation (S) group, model (M) group, low-dose remifentanil (L) group and high-dose remifentanil (H) group, with 15 rats in each group. The rat model of myocardial ischemia-reperfusion injury was established by the ligation of the left anterior descending branch (LAD). After ischemia for 30 min and reperfusion for 24 h, the cardiac function of rats in each group was measured by an ultrasonic instrument. Triphenyl tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats in each group. The activity of myocardial enzymes in the serum of rats in each group was detected. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to examine the apoptosis level of rat cardiomyocytes in each group. Quantitative polymerase chain reaction (qPCR) and Western blotting were applied to detect the expression levels of apoptosis-related proteins and messenger ribonucleic acids (mRNAs) in rat cardiomyocytes in each group. RESULTS: Compared with those in S group, left ventricular internal dimension in systole (LVIDs) and left ventricular internal dimension in diastole (LVIDd) were markedly increased (p<0.01), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were notably decreased in M group (p<0.01). LVIDs and LVIDd in L group and H group were lower than those in M group (p<0.05, p<0.01), whereas LVEF and LVFS were higher than those in M group (p<0.05, p<0.01). The myocardial infarction area in M group was significantly larger than that in S group (p<0.01), and those in L group and H group were remarkably smaller than that in M group (p<0.05, p<0.01). The activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase-muscle/brain (CK-MB) in the serum of rats in M group were evidently higher than those in S group (p<0.01), and compared with those in M group, those in L group and H group were significantly decreased (p<0.05, p<0.01). The apoptosis level of myocardial cells in M group was significantly higher than that in S group (p<0.01), while those in L group and H group were markedly lower than that in M group (p<0.05, p<0.01). Compared with those in S group, the expression levels of cleaved caspase-3 and its mRNAs in myocardial cells in M group were remarkably increased (p<0.01), while those of Bcl-2/Bax and it mRNAs were significantly decreased (p<0.01). The expression levels of cleaved caspase-3 and its mRNAs in myocardial cells in L group and H group were significantly lower than those in M group (p<0.05, p<0.01), but those of Bcl-2/Bax and its mRNAs were significantly higher than those in M group (p<0.05, p<0.01). CONCLUSIONS: Remifentanil can effectively reduce myocardial cell injury caused by myocardial ischemia-reperfusion in rats, improve cardiac function, reduce the myocardial infarction area, decrease cleaved caspase-3 in myocardial cells, and increase Bcl-2/Bax.

Discovery and identification of fatigue-related biomarkers in human saliva.

OBJECTIVE: To identify stable and specific biomarkers/biomarker combinations for fatigue assessment and establish a discriminant model. PATIENTS AND METHODS: Saliva was collected and electroencephalogram analysis was performed for 47 emergency physicians while awake and after continuoutas duty for 18-24 h. Physicians were divided into the fatigue and non-fatigue groups. Protein spectra of completely quantified saliva specimens were identified before and after long working hours using mass spectrometry. Data were analyzed through Proteome Discoverer software combined with SEQUEST to search protein databases. Proteins were characterized by collision-induced dissociation spectra. A global internal standard (GIS) was added to each group of samples and labeled by tandem mass tags m/z 131.1. All data were compared with GIS, and data between groups were further compared. Qualitative and quantitative data on proteins were exported for fatigue-related proteomic analysis, and a fatigue assessment model was established. RESULTS: We identified 767 salivary proteins in the fatigue group. The correct rates of the discriminant function of the non-fatigue and fatigue groups were 97.1% and 91.7%, respectively (the total correct rate was 95.7%). CONCLUSIONS: We identified 30 fatigue-related protein markers from saliva. We also established a fatigue assessment model for emergency physicians using salivary biomarkers.

Efficacy of inhalational sevoflurane anesthesia induction on inhibiting the stress response to endotracheal intubation in children with congenital heart disease.

OBJECTIVE: To investigate the efficacy of inhalational sevoflurane anesthesia induction on inhibiting the stress response to endotracheal intubation in pediatric patients with congenital heart disease (CHD). PATIENTS AND METHODS: Forty ASA physical status I/II pediatric patients scheduled for interventricular septal defect repair or interatrial septal defect repair, were randomly divided into two groups (20 each): intravenous induction group (Group C) and inhalational sevoflurane anesthesia induction group (Group D). In group C, anesthesia was induced with midazolam, pipecuronium bromide and fentanyl, and the children were examined by radial artery monitoring after the consciousness extinction. Also, they were endotracheally intubated after muscle relaxation. In group D, anesthesia was induced with inhalation of 8% sevoflurane and 6 L/min oxygen, and the children were examined by radial artery monitoring after the consciousness extinction and were endotracheally intubated 4 min later. Before anesthesia induction (T0), consciousness extinction (T1), endotracheal intubation (T2), endotracheal intubation (T3), and after endotracheal intubation (T4), 1 and 3 min after intratracheal intubation (T5,6), HR and bispectral index (BIS) were monitored. The MAP of T2-T6 points was recorded. Ulnar vein blood samples were taken for determination of Endothelin (ET) and Thromboxane A2(TXA2) in the points of consciousness extinction, and 5 and 10 min after endotracheal. RESULTS: All the children were well examined by endotracheal intubation. Compared with the baseline value at T0, there was no significant difference of HR in group D, but the HR of group C was decreased at T2, T3, T4 and T6. The BIS of the two groups were decreased at T1-T6 (p<0.05). Compared with the values at T2, they were increased at T5 and T6 in group C, and increased at T6 in group D (p<0.05). Compared with group C, the MAP of group D was decreased at T5, and the BIS of the two groups was decreased at T2-T6 (p<0.05). There were no significant differences of ET and TXA2 between groups. CONCLUSIONS: It is well inhibited the endotracheal intubation stress response in children with congenital heart diseases using sevoflurane inhalational anesthesia induction.

Correlation of insulin-like growth factor 1 and osteoarthritic cartilage degradation: a spontaneous osteoarthritis in guinea-pig.

OBJECTIVE: The pathogenesis of osteoarthritis centers on the imbalance between catabolic and anabolic processes in cartilage metabolism. Insulin growth factor 1 (IGF-1) has been shown to have anabolic effects in cartilage in vitro. This study aim to determine whether IGF-1 on cartilage is associated with loss of chondrocyte and extracellular matrix breakdown using the Hartley guinea pig model. MATERIALS AND METHODS: Cartilage from the medial and lateral tibial plateau of 6-month and 12-month old Hartley guinea pigs were used for this study. Histological analysis was performed with hematoxylin-eosin (HE) and toluidine blue staining. Safranin-O staining was used to quantify proteoglycan (PG) loss and the extent of cartilage damage by Modified Mankin score. Distribution of IGF-1 was demonstrated with in situ hybridization techniques. IGF-1 mRNA levels were assessed using Real-time PCR. RESULTS: Histological loss of chondrocytes, and cartilage matrix and decreased IGF-1 distribution were demonstrated in a temporal and spatial manner. Compared to the 6-month old samples, the 12-month specimens had significantly cartilage degeneration and less cartilage matrix and PGs staining. Decreased level of IGF-1 was also observed in the 12-month samples. These observations were more pronounced in the medial tibial plateau when compared to the lateral plateau. CONCLUSIONS: The decreased level of IGF-1 may play a critical role for maintaining the balance between catabolic and anabolic processes in cartilage metabolism during the development of osteoarthritis. Thus, the increase of IGF-1 may be applicable to developing OA therapy.

Clinical research on correction of ankle arthritis-related factor levels via urea.

OBJECTIVE: To investigate the reliability of urea as the internal reference of ankle irrigating fluid in correction of synovial fluid and related factor concentration dilution times, and to further determine the factor expression level in synovial fluid. PATIENTS AND METHODS: A total of 91 patients, including 20 cases of non-posterior median foot lesions and 71 cases of unilateral ankle osteoarthritis, were enrolled in this study. AOFAS score, Takakura staging and visual analogue pain scale were given; the venous blood was collected and the ankle fluid and irrigating fluid were obtained from the affected side via puncture. The urea in serum, synovial fluid and irrigating fluid was quantified using an AU5800 biochemical instrument (Beckman Coulter). Statistical analysis was performed for the correlation between urea in serum and synovial fluid; the levels of TNF-α, IL-1ß, IL-6, IGF-1 and HELIX-II in irrigating fluid quantified by enzyme linked immunosorbent assay (ELISA) were further corrected. RESULTS: There was a good linear relationship between urea contents in synovial fluid and serum (R2=0.89), and the regression slope was 0.927. The levels and ratio of urea in serum and synovial fluid were independent of Takakura staging or pain degree. The expressions of IL-1ß (p=0.000), IGF-1 (p=0.000) and HELIX-II (p=0.010) were significantly increased in synovial fluid in patients with ankle osteoarthritis. There was no significant difference in expression of IL-1ß (p=0.514), and TNF-α was not detected in synovial fluid. CONCLUSIONS: This study confirmed the dynamic stability of urea in the ankle fluid, and it is not affected by the progression of arthritis, age and other factors, which is the standard internal reference of correcting ankle irrigating fluid dilution times. The occurrence mechanism of ankle osteoarthritis may be different from that of other osteoarthritis, and IL-6 and IGF-1 are associated with the progression of the disease. Increased HELIX-II is an independent factor of predicting cartilage injury.

Thrombolysis of deep vein thrombosis and inhibiting chemotaxis of macrophage by MCP-1 blockage.

OBJECTIVE: Deep vein thrombosis (DVT) is one common vascular complication after trauma or surgery. Macrophage plays an important role in recanalization of thrombosis and monocyte chemotactic protein 1 (MCP-1) has a potent chemotactic role for macrophage. This study investigated the role of MCP-1 and macrophage in DVT thrombolysis. MATERIALS AND METHODS: DVT mice model was established for evaluating thrombosis grades, and divided into DVT, DVT + MCP-1 recombinant protein, and DVT + MCP-1 neutralizing antibody groups. MCP-1 mRNA and protein expression, weight/length ratio of thrombosis were tested at 1, 5, 9 and 15 day after DVT. F4/80 protein expression in thrombosis on day 9 was measured to reflect infiltration of macrophage. RESULTS: DVT model mice had thrombosis grade at 2.47 ± 0.22 whilst no thrombosis occurred in sham group. DVT group had gradually increased MCP-1 mRNA and protein expression, which reached the peak at day 9, followed by decreased expression. Thrombosis weight/length ratio showed decreasing trends. MCP-1 protein injection significantly elevated MCP-1 expression, decreased thrombosis weight/length ratio, and elevated macrophage infiltration. Injection of MCP-1 antibody remarkably decreased MCP-1 expression, elevated thrombosis weight/length ratio and macrophage infiltration. CONCLUSIONS: MCP-1 up-regulation participates in macrophage chemotaxis and thrombolysis after DVT formation. The blockade of MCP-1 weakens its thrombolysis effects.

Distinctive effect of 6% hydroxyethyl starch 130/0.4 (Voluven) infusion on pediatric patients with congenital heart disease.

OBJECTIVE: It has not been clear that Voluven (6% hydroxyethyl starch 130/0.4) may be administered in pediatric patients safely. The purpose of this study was to determine if Voluven could be used for blood volume expansion and hypovolemia prevention in pediatric patients with congenital heart disease. PATIENTS AND METHODS: 50 pediatric patients with congenital heart disease were recruited in the study. Circulatory and respiratory parameters were determined to monitor the responses to intravenous infusion of Voluven in the patients. RESULTS: Intravenous infusion of Voluven significantly increased levels of colloid osmotic pressure and central venous pressure, but decreased levels of hemoglobin in the patients. Voluven infusion did not significantly affect colloid osmotic pressure, central venous pressure, hemoglobin and heart rate in the preschool children (<6 years old), and similarly, low infusion (100-240 mL per patient) of Voluven did not significantly affect colloid osmotic pressure, central venous pressure, hemoglobin and heart rate in the young child patients. Also, there was the similar response, i.e. increased colloid osmotic pressure, to Voluven infusion in both female child patients and patients with atrial septal defect. CONCLUSIONS: Voluven may be used in pediatric patients with congenital heart disease, but not in the preschool child patients. Furthermore, special attention should be paid to the intravenous administration of Voluven for blood volume expansion and hypovolemia prevention in female pediatric patients and child patients with atrial septal defect.

Exposure to fine particulate matter associated with senile lentigo in Chinese women: a cross-sectional study.

BACKGROUND: Skin ageing especially senile lentigo directly affects self-esteem. For decades, senile lentigo has been associated with chronic exposure to solar radiation. However, a study conducted recently in Caucasian subjects suggested that exposure to air pollution was significantly correlated with extrinsic skin ageing, in particular senile lentigines. OBJECTIVE: To investigate the association between fine particulate matter (PM2.5 ) and skin ageing, particularly senile lentigo and seborrheic keratosis. METHODS: The study enrolled 400 Chinese women aged 40-90 years including 210 from the Yanqing county in Beijing (low PM2.5 exposure group) and 190 from the Xuanwumen in Beijing (high PM2.5 exposure group). Skin ageing symptoms, particularly senile lentigines and seborrheic keratoses, were clinically assessed using scores of intrinsic and extrinsic skin ageing. An ordinal logistic regression model was used to analyse the effect of PM2.5 on skin ageing adjusted for factors underlying skin ageing. RESULTS: In the study population of Xuanwumen, we found that senile lentigo on cheeks and back of hands was 1.48 times and 2.8 times higher, respectively, compared with those from Yanqing county. However, no association was found between PM2.5 and seborrheic keratosis. We found that other variables such as smoking, second-hand smoking, contact with fossil fuels and skin types were significantly associated with skin ageing. CONCLUSION: These results indicate that PM2.5 was another extrinsic factor promoting skin ageing.

Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study.

BACKGROUND: This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF-α inhibitor, adalimumab, for Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In the 12-week, double-blind, placebo-controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every-other-week (following a single 80 mg dose), or placebo every-other-week. In the subsequent 12-week, open-label, Period B, all patients received adalimumab 40 mg every-other-week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug. RESULTS: For the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All-adalimumab Population), treatment-emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All-adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients each]. There was one death (chronic heart failure). CONCLUSION: In these Chinese patients with moderate-to-severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.

Changes in Ocean Heat, Carbon Content, and Ventilation: A Review of the First Decade of GO-SHIP Global Repeat Hydrography.

Global ship-based programs, with highly accurate, full water column physical and biogeochemical observations repeated decadally since the 1970s, provide a crucial resource for documenting ocean change. The ocean, a central component of Earth's climate system, is taking up most of Earth's excess anthropogenic heat, with about 19% of this excess in the abyssal ocean beneath 2,000 m, dominated by Southern Ocean warming. The ocean also has taken up about 27% of anthropogenic carbon, resulting in acidification of the upper ocean. Increased stratification has resulted in a decline in oxygen and increase in nutrients in the Northern Hemisphere thermocline and an expansion of tropical oxygen minimum zones. Southern Hemisphere thermocline oxygen increased in the 2000s owing to stronger wind forcing and ventilation. The most recent decade of global hydrography has mapped dissolved organic carbon, a large, bioactive reservoir, for the first time and quantified its contribution to export production (∼20%) and deep-ocean oxygen utilization. Ship-based measurements also show that vertical diffusivity increases from a minimum in the thermocline to a maximum within the bottom 1,500 m, shifting our physical paradigm of the ocean's overturning circulation.