The role of the cd99l2 gene on leukocyte interstitial migration in zebrafish.

Leukocytes play an essential role in ontogeny, tissue regeneration, and innate and adaptive immunity. The migration of leukocytes to the infected or traumatized areas is necessary for their immune response function. As an adhesion molecule, CD99L2 is crucial in the extravasation of leukocytes, however, its role in the interstitial migration of leukocytes remains unclear. In this study, the cd99l2 gene was knock-out by TALEN (transcription activator-like effector nuclease) in zebrafish and discovered that the deletion had no effect on zebrafish development. The number of granulocytes and macrophages recruited to the wounded tissue was significantly reduced in the cd99l2 mutants following caudal fin damage. Further research revealed that the expression of mfap4 was drastically decreased in the cd99l2 mutants, which may be one of the reasons that affect the migration of macrophages to the wound site. Moreover,transgenic lines with labeled vasculature, neutrophils and macrophages demonstrated that neutrophils and macrophages migrate throughout the interstitial space to the wound tissue in both wild-type and mutant zebrafish at 60 hours post-fertilization, indicating that the cd99l2 gene is involved in the interstitial migration of leukocytes. Finally, RNA transcription, protein folding, and the P450 pathway were enriched in cd99l2 mutants by RNA-seq analysis. Previous research had demonstrated that the regulation of transcription and signal transduction could be affected by adhesion molecules, which may suggest that the cd99l2 gene is involved in the cascade signaling pathway of leukocyte migration as an adhesion molecule. In conclusion, this study uncovered a novel function of the cd99l2 gene in the process of leukocyte migration in zebrafish, which is expected to provide a theoretical foundation for inflammatory and immune-related diseases.

[Induction of robust senescence-associated secretory phenotype in mouse NIH-3T3 cells by mitomycin C].

Senescence-associated secretory phenotype (SASP) is often a concomitant result of cell senescence, embodied by the enhanced function of secretion. The SASP factors secreted by senescent cells include cytokines, proteases and chemokines, etc, which can exert great influence on local as well as systemic environment and participate in the process of cell senescence, immunoregulation, angiogenesis, cell proliferation and tumor invasion, etc. Relative to the abundance of SASP models in human cells, the in vitro SASP model derived from mouse cells is scarce at present. Therefore, the study aimed to establish a mouse SASP model to facilitate the research in the field. With this objective, we treated the INK4a-deficient mouse NIH-3T3 cells and the wildtype mouse embryonic fibroblasts (MEF) respectively with mitomycin C (MMC), an anticarcinoma drug which could induce DNA damage. The occurring of cell senescence was evaluated by cell morphology, ß-gal staining, integration ratio of EdU and Western blot. Quantitative RT-PCR and ELISA were used to detect the expression and secretion of SASP factors, respectively. The results showed that, 8 days after the treatment of NIH-3T3 cells with MMC (1 µg/mL) for 12 h or 24 h, the cells became enlarged and the ratios of ß-gal-positive (blue-stained) cells significantly increased, up to 77.4% and 90.4%, respectively. Meanwhile, the expression of P21 protein increased and the integration ratios of EdU significantly decreased (P < 0.01). Quantitative RT-PCR detection showed that the mRNA levels of several SASP genes, including IL-6, TNF-α, IL-1α and IL-1ß increased evidently. ELISA detection further observed an enhanced secretion of IL-6 (P < 0.01). On the contrary, although wildtype MEF could also be induced into senescence by MMC treatment for 12 h or 24 h, embodied by the enlarged cell volume, increased ratios of ß-gal-positive cells (up to 71.7% and 80.2%, respectively) and enhanced expression of P21 protein, the secretion of IL-6 displayed no significant change. Our study indicated that, although MMC could induce senescence in both mouse NIH-3T3 cells and wildtype MEF, only senescent NIH-3T3 cells displayed the canonical SASP phenomena. Current study suggested that senescent NIH-3T3 cells might be an appropriate in vitro SASP model of mouse cells.

[Screening of Active Fractions from Huanglian Jiedu Decoction against Primary Neuron Injury after Oxygen-Glucose Deprivation].

OBJECTIVE: To observe the protective effect of active fractions of Huanglian Jiedu Decoction (HJD) on primary cortical neuron injury after oxygen-glucose deprivation (OGD)/reperfusion (R) injury. Methods Using macroporous resin method, HJDFE30, HJDFE50, HJDFE75, and HJDFE95 with 30%, 50%, 75%, and 95% alcohol were respectively prepared. Then the content of active components in different HJD fractions was determined with reverse phase high-performance liquid chromatography (RP-HPLC). The OGD/R injury model was induced by sodium dithionite on primary cortical neurons in neonate rats. MTT assay was used to observe the effect of four fractions (HJDFE30, HJDFE50, HJDFE75, and HJDFE95) and seven index components of HJD on the neuron viability. RESULTS: RP-HPLC showed active component(s) contained in HJDFE30 was geniposide; baicalin, palmatine, berberine, and wogonside contained in HJDFE50; baicalin, berberine, baicalein, and wogonin contained in HJDFE75. The neuron viability was decreased after OGD for 20 min and reperfusion for 1 h, (P <0. 01), and significantly increased after administered with HJD, HJDFE30, HJDFE50, and HJDFE75 (P <0. 05, P <0. 01). Geniposide, baicalin, baicalein, palmatine, wogonside, and wogonin could increase the cortical neuron viability (P <0. 05, P <0. 01). CONCLUSIONS: HJDFE30, HJDFE50, and HJDFE75, as active fractions of HJD, had protective effect on primary cortical neuron injury after OGD/R. Furthermore, geniposide, baicalin, and baicalein were main active components of HJD.

Two-step irradiance schedule versus single-dose tramadol sustained-release tablets for pain control during topical 5-aminolevulinic acid-photodynamic therapy of condyloma acuminatum in Chinese patients: a randomized comparative study.

BACKGROUND AND OBJECTIVE: Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) offers promising results for the treatment of condyloma acuminatum. However, patients have to dwell with pain to benefit from this otherwise effective and safe "off-label" treatment modality. Several techniques have been explored to control ALA-PDT-induced pain, but the desperate search for a universally accepted method is still ongoing. This study compares the two-step irradiance approach with single-dose administration of 100 mg tramadol sustained-release tablets for pain induced by ALA-PDT of condyloma acuminatum in Chinese patients. PATIENTS AND METHODS: Adult Chinese patients with condyloma acuminatum were enrolled in a randomized comparative study. Pain levels were compared using the Numeric Rating Scale (NRS) at pre-defined assessment points during and after irradiation. RESULTS: The pain was dominated by characteristics such as burning and pricking and was almost always local and superficial. DURING IRRADIATION: The median pain scores were lower in the two-step irradiance group at 1 minute (U = 621.5, P = 0.002) but higher at 20 minutes (U = 585.5, P = 0.002). The median pain scores between the two groups did not differ significantly at other assessment points. The pain was moderate in both groups and peaked earlier in the analgesics group (median: 5 minutes) but later in the two-step irradiance group (median: 15 minutes). AFTER IRRADIATION: The pain was generally mild. The median pain scores were equal at each assessment point, except at 3 hours where the median was lower in the analgesics group (1.0) as compared with the two-step irradiance group (2.0) (U = 725.0, P = 0.056). CONCLUSIONS: Pain in the two-step irradiance protocol is irradiance-dependent. The two-step irradiance approach produces significant benefits over analgesics during the initial stages of therapy but analgesics offer significant benefits thereafter. There are potential benefits of combining the two approaches in minimizing ALA-PDT-induced pain.

Evaluating Skin Involvement in Systemic Sclerosis Using High-Frequency Ultrasound and Virtual Touch Tissue Imaging.

OBJECTIVE: This study aimed to explore the diagnostic significance of high-frequency ultrasound combined with visual touch tissue imaging quantification (VTIQ) in the diagnosis and management of systemic sclerosis (SSc). METHODS: Patients diagnosed with SSc and normal volunteers were recruited and divided into an experimental group and a control group, with 30 cases in each group, respectively. The skin thickness at six sites was assessed using high-frequency ultrasound, and the shear wave velocity (SWV) was determined using the VTIQ method. The differences in skin thickness and SWV between the experimental group and the control group were compared and a receiver operating characteristic (ROC) curve was plotted. The value of high-frequency ultrasound, VTIQ, and high-frequency ultrasound combined with VTIQ for evaluating skin involvement in SSc was determined. RESULTS: The difference in SWV sum at six sites and the thickness sum was statistically significant (all p = 0.000 < 0.05) from that of the control group, and there was a strong association between the SWV sum, thickness sum, and Rodnan skin score at the six sites in the experimental group (p = 0.000, r = 0.726; p = 0.000, r = 0.679). Based on the ROC curve, the area under the curve (AUC) for high-frequency ultrasound examination was 0.789. The AUC for VTIQ examination was 0.893, while the AUC for high-frequency ultrasound combined with VTIQ examination was 0.923. The combined examination method showed the highest AUC, indicating the best diagnostic performance. CONCLUSION: The integration of high-frequency ultrasound and VTIQ provides a quantitative approach for assessing the extent of skin involvement in SSc patients, offering valuable insights for clinical diagnosis and treatment purposes.

[Adverse cardiovascular effects of antiretrovirals in female mice during gestation].

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

[The time-concentration relationship of serum bisphenol A in male rats].

OBJECTIVE: To investigate the relationship of time-concentration of bisphenol A (BPA) in male Sprague-Dawley (SD) rats after single oral BPA administration. METHODS: A total of 66 specific pathogen free (SPF) SD male rats were divided into 10 experimental groups and control group (n = 6). The experimental group rats were treated with BPA of 300 mg/kg by oral gavage and blood samples were taken from one group at 0.5, 1, 2, 4, 6, 12, 24, 36, 60, 84 h time point after oral administration, respectively. The serum BPA concentration was determined by fluorescence-high performance liquid chromatography (FL-HPLC) analysis. RESULTS: After oral administration of 300 mg/kg, the total serum BPA concentration of 17.13 microg/ml was the highest in rats at 1 h, then decreased, but it increased to 15.18 microg/ml again at 24 h, then gradually decreased to 0.51 microg/ml at 84 h. The level of serum free BPA was lower than that of total serum BPA after oral administration, the serum free BPA was 0.57 microg/ml at 0.5 h after oral administration. The serum free BPA level decreased to 0.06 microg/ml at 1 h, 0.03 microg/ml at 4 h, 0.01 microg/ml at 36 h after oral administration. The free BPA was only 4.15% (0.57/13.73) in total BPA in serum at 0.5 h after oral administration of 300 mg/kg BPA. CONCLUSION: These results suggested that conjugated BPA was the main metabolite of BPA in rat serum after single oral administration. Enterohepatic circulation of BPA glucuronide in rats may results in two peak levels of total BPA in serum.

[The differences in absorption and metabolism of bisphenol A between rats and mice].

OBJECTIVE: To investigate the mechanism of the different levels of serum bisphenol A (BPA) between rat and mouse after oral administration. METHODS: A total of 18 specific pathogen free (SPF) male rats and 18 mice were treated with 300 mg/kg BPA by oral administration, blood samples were taken from rats and mice after BPA administration at 0.5, 1.0, 12.0 h time points (n = 6 at each point). Serum BPA levels were quantified using fluorescence-high performance liquid chromatography (FL-HPLC) analysis. The rats and mice (n = 6, respectively) were perfused with 100 ml of 0.1 mmol/L BPA by intestinal absorption in situ, then the BPA levels of perfusion fluid at 0.5, 1.0, 2.0 h time points and serum at 2.0 h after BPA perfusion were determined by FL-HPLC analysis. The levels of UDP-glucuronosyltransferase 2B1 (UGT2B1) mRNA expression in the liver of rats and mice were analyzed by semi-quantitative RT-PCR and UGT2B1 enzymatic activity was determined by FL-HPLC method. The rats and mice (n = 6, respectively) were treated with 300 mg/kg BPA by oral administration after fasting 24 h, the feces were collected during 24 h and the levels of BPA in feces were determined by FL-HPLC analysis. RESULTS: At 0.5, 1.0, 12.0 h after oral administration at 300 mg/kg BPA, the levels of serum BPA in mice ((66.57 ± 14.95), (51.16 ± 16.06), (22.73 ± 5.00) µg/ml, respectively) were significantly higher than in rats ((15.63 ± 5.65), (18.34 ± 5.02), (7.65 ± 2.58) µg/ml, respectively) (F values were 50.660, 17.957, 8.420, respectively, P < 0.05), the rates of absorption in mice small intestine during 0 h-, 0.5 h-, 1.0 - 2.0 h ((10.20 ± 4.20), (1.49 ± 0.67), (1.31 ± 0.55) µg × cm(-2) × min(-1), respectively) were higher than that in rats ((1.87 ± 0.69), (0.47 ± 0.13), (0.36 ± 0.08) µg × cm(-2) × min(-1), respectively) (F values were 14.954, 8.877, 11.536, respectively, P < 0.05), the serum BPA levels in mice ((22.64 ± 4.35) µg/ml) were significantly higher than in rats ((4.13 ± 0.83) µg/ml) after 2 h perfusion with 0.1 mmol/L BPA (F = 74.643, P = 0.000), the levels of UGT2B1 mRNA expression and enzymatic activity in the rats liver were obviously higher than in the mice liver. After oral administration at 300 mg/kg BPA, the feces BPA levels of rats ((1.50 ± 0.32) mg/g) were significantly higher than that of the mice ((0.57 ± 0.35) mg/g) (F = 21.215, P = 0.001) during 24 h. CONCLUSION: The serum BPA level of mouse is significantly higher than the rat after oral administration at 300 mg/kg BPA, which may be caused by BPA high absorption rate of mouse small intestine and strong ability of BPA glucuronidation and excretion of the rat.

[Changes of semen quality in Chinese fertile men from 1985 to 2008].

OBJECTIVE: To analyze the changes of semen quality in Chinese fertile men during the past 24 years. METHODS: We reviewed the literature on the sperm quality of Chinese fertile males published from 1985 to 2008, collected relevant data, and analyzed the changes in semen volume, sperm density, and total sperm count by linear regression. RESULTS: There were no significant changes either in semen volume during the period of 1985-2008 (P >0. 05) , or in sperm density and total sperm count from 1985 to 1994 (P > 0.05). However, significant decreases were observed during the latter 14 years in sperm density (from 81.5 x 10(6)/ml in 1995 to 66.7 x 10(6)/ml in 2008, with a mean annual reduction of 1.40%) and total sperm count (from 257.2 x 10(6) in 1995 to 185.9 x 10(6) in 2008, with a mean annual reduction of 2. 15%) (P < 0.05). CONCLUSION: The semen quality of Chinese fertile men showed no significant changes from 1985 to 1995, but evidently declined from 1995 to 2008, which may be attributed to the aggravated environmental pollution induced by heavy chemical industry.

[Acute infection of Toxoplasma gondii affects the level of oxygen free radicals in serum and testes of mice].

OBJECTIVE: To observe the impact of Toxoplasma gondii infection on the level of oxygen free radicals and antioxidant enzyme in serum and testes of mice. METHODS: 40 BALB/c male mice were randomly divided into four groups. Five mice from each group were injected intraperitoneally with 2.5 x 10(3) tachyzoites of T. gondii, the others received PBS. Mice were sacrificed on the 1st, 3rd, 5th, and 7th day after inoculation. Samples of serum and testes were collected to determine the content of oxygen free radicals and superoxide dismutase (SOD). RESULTS: The concentration of the oxygen free radicals (NO, *OH, O2-) in serum and testes of the mice increased along with the days of infection. The concentration of SOD reached a peak on the 3rd day after the injection and then decreased. Both of oxygen free radicals and SOD showed a statistical difference with the control (P < 0.01). CONCLUSION: Acute infection of T. gondii leads to n increase of oxygen free radicals and SOD in the serum and testes of mice.

The traditional uses, phytochemistry, pharmacology and toxicology of Cinnamomi ramulus: a review.

OBJECTIVES: Cinnamomi ramulus (called Guizhi in Chinese) is a traditional medicine used to treat gastrointestinal dysfunction, cancer, arthritis, osteoporosis, spleen deficiency, Alzheimer's disease and obesity. This review aimed to provide a systematic summary on the geographical distribution, botany, traditional application, phytochemistry, pharmacology, pharmacokinetics, toxicology and other aspects of Cinnamomi ramulus. KEY FINDING: So far, more than 121 chemical compounds have been isolated from Cinnamomi ramulus, including volatile oil, organic acids, triterpenoid saponins, coumarins, tannins, flavonoids and flavonoid glycosides, steroids and polysaccharides. This paper reviews the pharmacological effects of Cinnamomi ramulus on antibacterial, anti-inflammatory, antiviral, antitumour, antipyretic and analgesic, antidiabetic and antiplatelet aggregation effects. Furthermore, the present review also indicates that Cinnamomi ramulus has the potential to develop into drugs for treating various diseases with high efficacy and low toxicity. SUMMARY: The convictive evidence from modern pharmacology research supports the traditional application of Cinnamomi ramulus. However, further studies on the structure-activity relationship of some of the isolated compounds may improve their biological potency. More toxicological studies will also contribute to the progress of clinical trial studies.

[Expression and Clinical Significance of PD-L1 and MicroRNA-138-5p in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the expression and clinical significance of PD-L1 and microRNA-138-5p in the peripheral blood mononuclear cells of patients with acute myeloid leukemia. METHODS: The SYBR GreenⅠreal-time PCR was used to detect the expression levels of PD-L1 mRNA and miR-138 in 20 cases of primary AML, 9 cases of relapsed/refractory AML and 8 cases of complete remission. The samples of peripheral blood of 20 healthy peoples were used as controls. RESULTS: The expression levels of PD-L1 in both the primary AML and the relapsed/refractory AML groups were significantly higher than those in the healthy control group (P<0.01), and the expression level of PD-L1 in the relapsed/refractory AML group was significantly higher than that in the primary AML group (P<0.01). The expression level of miR-138 in both the primary AML and the relapsed/refractory AML groups were significantly lower than that in the healthy control group (P<0.01). The 8 sampes out of 20 cases of primary AML patients achieved complete remission (CR) were collected and detected. The results showed that the expression level of miR-138 in the complete remission group was higher than that in the primary AML group (P<0.05), but the expression level of PD-L1 mRNA in the CR group was not significantly different from that in the primary AML group (P>0.05). and there was a negative correlation between PD-L1 mRNA and miR-138 in primary AML patients (P<0.05). CONCLUSION: The expression of PD-L1 increases and the expression of miR-138 down-regulates in PBMNCs of AML patients, furthermore, both correlate each other.

Targeted Acquisition of Fusarium oxysporum f. sp. niveum Toxin-Deficient Mutant and Its Effects on Watermelon Fusarium Wilt.

Watermelon Fusarium wilt is a common soil-borne disease that has significantly affected its yield. In this study, fusaric acid-deficient mutant designated as ΔFUBT (mutated from Fusarium oxysporum f. sp. niveum, FON) was obtained. The ΔFUBT mutant showed significant decrease in fusaric acid production but maintained wild-type characteristics, such as in vitro colony morphology, size, and conidiation. A field pot experiment demonstrated that ΔFUBT could successfully colonize the rhizosphere and the roots of watermelon, leading to significant reduction in FON colonization in the watermelon plant. In addition, ΔFUBT inoculation significantly improved the rhizosphere microenvironment and effectively increased the resistance in watermelon. This study demonstrated that a nonpathogenic Fusarium mutant (ΔFUBT) could be developed as an effective microbial control agent to alleviate Fusarium wilt disease in watermelon and increase its yield.

[Long-term effects of bio-organic fertilizer application on soil organic carbon pool and enzyme activity of cucumber continuous cropping.] / æ–½ç”¨ç”Ÿç‰©æœ‰æœºè‚¥å¯¹é»„ç“œè¿žä½œåœŸå£¤æœ‰æœºç¢³åº“å’Œé ¶æ´»æ€§çš„æŒç»­å½±å“.

The combination of field trial and indoor incubation experiment were conducted to examine the long-term effects of one-time application of bio-organic fertilizer on soil organic carbon (C) components, organic C mineralization, and enzyme activity in cucumber continuous cropping. Compared with CK, bio-organic fertilizer application significantly increased the content of soil organic C, activated C pool, slow-release C pool and inert C pool during four continuous cucumber planting seasons. With the increases of the number of consecutive crops, the proportion of soil inert carbon gradually increased. After four continuous seasons of cucumber planting, the cumulative and daily mineralization rate of soil organic C in the bio-organic fertilizer treatment increased by 17.3%-31.0% and 7.8%-43.0%, respectively. In the stage of cucumber ripening, bio-organic fertilizer application increased the activities of continuous soil urease, catalase, sucrose and neutral phosphatase by 10.5%-62.1%, 4.8%-25.5%, 3.9%-21.4% and 4.6%-66.4%. The activities of those four enzymes increased with the increases of the application amount of organic fertilizer. Results from the correlation and path analysis showed that the activity of the four enzymes were significantly correlated with the dynamics of organic carbon components in soil cucumber continuous cropping process. Soil urease and invertase activities significantly affected organic carbon mineralization during the continuous cropping process of cucumber. Application of bio-organic fertilizer could increase soil organic carbon content and enzyme activity, improve inert carbon ratio of soil organic carbon pools, cumulative and mineralization rate of organic carbon in continuous cropping process, thereby enhance soil carbon sequestration capacity.

Impact of C-reactive protein on long-term mortality in acute myocardial infarction patients with diabetes and those without.

BACKGROUND: Little is known about the relationship between C-reactive protein (CRP) and long-term mortality after acute myocardial infarction (AMI) in diabetic patients. The current study aimed to examine whether CRP levels are associated with for long-term all-cause, cardiovascular, and cardiac mortality in AMI patients with diabetes and those without separately. METHODS: The cohort study included 663 diabetic and 1853 non-diabetic patients with AMI. The median follow-up time was 1045 days (2.9 years). RESULTS: According to the median concentration of serum CRP (8.95 mg/l), the patients were divided into two groups. The low CRP level group (<8.95 mg/l) served as a reference. In diabetic patients with AMI, the adjusted hazard ratios (HRs) for long-term all-cause, cardiovascular, and cardiac mortality were 1.62 (P = 0.027), 1.91 (P = 0.008), and 2.08 (P = 0.007), respectively. In non-diabetic patients with AMI, the adjusted hazard ratios (HRs) for long-term all-cause, cardiovascular, and cardiac mortality were 1.72 (P < 0.001), 1.8 (P < 0.001), and 1.78 (P = 0.001), respectively. CONCLUSIONS: Regardless of whether patients had diabetes or not, CRP value is an independent predictor of long-term, all-cause, cardiovascular, and cardiac mortality after AMI.

Impact of serum albumin levels on long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset acute myocardial infarction.

BACKGROUND: To evaluate the association of serum albumin (SA) with long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset acute myocardial infarction (AMI). METHODS: The cohort study enrolled 2305 patients with first-onset AMI. The median follow-up was of 1088days (3years). Impacts of SA on long-time mortality after AMI were determined using multivariate Cox proportional hazard regression analysis with backward selection. RESULTS: The patients were divided into three categories by SA tertiles (≤3.62, 3.63-4.08, >4.08g/dl). High tertile group was used as reference, the adjusted HRs for all-cause death were 1.21 (P=0.338) and 1.74 (P=0.003) for intermediate and low tertile, respectively (p-for-trend=0.001); The equivalent values for cardiovascular death were 1.13 (P=0.588) and 1.64 (P=0.022), respectively (p-for-trend=0.009); The corresponding values for cardiac death were 1.07 (P=0.806) and 1.59 (P=0.048), respectively (p-for-trend=0.022). Moreover, adjusted HRs per 1-g/dl decrease in SA concentrations were 1.66 (P=0.001) for all-cause death, 1.47 (P=0.024) for cardiovascular death, and 1.61 (P=0.012) for cardiac death. CONCLUSIONS: Low SA level (≤3.62g/dl) on admission was an independent predictor of long-term all-cause, cardiovascular, and cardiac mortality in patients with first-onset AMI. There was a dose-response relationship between decreased SA concentrations and increased long-term all-cause, cardiovascular, and cardiac mortality.

Potential of endophytic fungus Phomopsis liquidambari for transformation and degradation of recalcitrant pollutant sinapic acid.

The biodegradation potential of sinapic acid, one of the most representative methoxy phenolic pollutants presented in industrial wastewater, was first studied using an endophytic fungus called Phomopsis liquidambari. This strain can effectively degrade sinapic acid in flasks and in soil and the possible biodegradation pathway was first systematically proposed on the basis of the metabolite production patterns and the identification of the metabolites by GC-MS and HPLC-MS. Sinapic acid was first transformed to 2,6-dimethoxy-4-vinylphenol that was further degraded via 4-hydroxy-3,5-dimethoxybenzaldehyde, syringic acid, gallic acid, and citric acid which involved in the continuous catalysis by phenolic acid decarboxylase, laccase, and gallic acid dioxygenase. Moreover, their activities and gene expression levels exhibited a 'cascade induction' response with the changes in metabolic product concentrations and the generation of fungal laccase significantly improved the degradation process. This study is the first report of an endophytic fungus that has great potential to degrade xenobiotic sinapic acid, and also provide a basis for practical application of endophytic fungus in the bioremediation of sinapic acid-contaminated industrial wastewater and soils.

[Value of MCV/RDW Combined with Reticulocyte Parameters in Differential Diagnosis of Anemia Diseases].

OBJECTIVE: To evaluate the value of mean corpuscular volume/RBC distribution width (MCV/RDW) combined with reticulocyte parameters in differential diagnosis of aplastic anemia (AA), myelodysplastic syndrome (MDS), megaloblastic anemia (MA) and hemolytic anemia (HA) in order to provide some laboratorial evidence for clinical doctors in first diagnosis of these diseases. METHODS: The data of MCV/RDW and reticulocyte parameters of AA, MDS, MA and HA patients from January 1 of 2011 to August 31 of 2014 were retrospectively collected in West China Hospital of Sichuan University. And 158 healthy unrelated individuals with age-, sex-matched were collected as controls. The value of MCV/RDW and reticulocyte parameters in differentiating diagnosis of above mentioned 4 kinds of anemia diseases was assessed. ROC analysis was used to determine the cutoff value of MCV/RDW and the reticulocyte parameters were performed in differentiating diagnosis of AA and MDS. RESULTS: The average values of MCV/RDW of 158 AA patients (79 acute AA patients and 79 chronic AA patients), 107 MDS patients, 13 MA patients and 81 HA patients increased in variable degrees as compared with the controls, and there was statistical difference between them, the MCV/RDW value of acute AA patients was obviously less than that of other patients. In the 4 kinds of anemia diseases, the reticulocyte absolute count in acute AA patients was the lowest, that of chronic AA, MA and MDS patients was higher, and that of HA patients was highest. The ratio of low fluorescent reticulocyte decreased, and the ratio of moderate and high fluorescent reticulocytes increased in the 4 kinds of anemia diseases, as compared to controls. The difference was statistically significant. The analysis of differential diagnosis of chronic AA and MDS showed that RDW-SD could differentiate the chronic AA from MDS. The area under the curve (AUC) of RDW-SD was 0.76 (P < 0.01). The cutoff value of RDW-SD was 22.75fl. The sensitivity and specificity of RDW-SD for differential of chronic AA and MDS was 49.5% and 98.7%, respectively. CONCLUSION: MCV/RDW and reticulocyte parameters can be used as the laboratorial differential diagnostic indicators for AA, MDS, MA and HA diseases.

R25G mutation in exon 1 of LMNA gene is associated with dilated cardiomyopathy and limb-girdle muscular dystrophy 1B.

BACKGROUND: Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy (DCM), conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype. METHODS: All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction (PCR) and the PCR products were screened for gene mutation by direct sequencing. RESULTS: Ten members of the family had limb-girdle muscular dystrophy (LGMD) and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C > G (R25G) in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine (Arg) to glycine (Gly). CONCLUSIONS: The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.