[A study of the clinical curative effect of nucleos(t)ide analogues treated to pegylated interferon-α add-on therapy in patients with chronic hepatitis B].

Objective: To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test. Results: A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance. Conclusion: Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log(10)IU/ml), HBsAg level at 24 weeks (≤ 0.92 log(10)IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log(10)IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log(10)IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

[The transformation of microcystin-LR during tap water treatment process and analysis of its degradation products].

Objective: To establish a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the determination of microcystin-LR (MC-LR) in drinking water, investigate its removal efficiency during tap water advanced treatment process and analyze its degradation products in the tap water. Methods: Two parallel water samples were collected from each point of tap water advanced treatment process in September 2015, November 2015 and January 2016, respectively, and treated by mixing, filtration, concentration, elution, nitrogen blow and re-dissolvement. The samples were analyzed by LC/MS/MS to determine the MC-LR concentration and its removal efficiency during treatment process. The combination of actual water enrichment (including source water enrichment of 50 times and 1 500 times concentrated, finished water enrichment of 50 times and 2 500 times concentrated) and laboratory simulated water (including the mixture of MC-LR and liquid chlorine in the mass ratio of 1∶10, 1∶20, 1∶100 and 1∶1 000, respectively) were used to qualitative analyze the MC-LR degradation products by Orbitrap mass spectrometry. Results: The linearity of MC-LR ranged from 2 to 200 µg/L with the detection limit of 0.007 9 µg/L and the limit of quantification of 0.026 3 µg/L. The recovery rate of MC-LR from different contration in drinking water were from 94.88%-101.47%. The intra-day precision was 2.51%-7.93% and the intra-day precision was 3.24%-8.41%. The average concentration of MC-LR in source water was (0.631±0.262) µg/L, 94.0% of which can be removed by ozone exposure while the concentrate was (0.038±0.016) µg/L, biological pre-treatment and chlorination. The remaining can hardly be removed by sand filtration, ozone exposure, activated carbon, ultrafiltration and other processes. The MC-LR average concentration in the finished water maintained at about (0.036±0.016) µg/L. Degradation products including hydroxy-microcystin, methyl-hydroxy-microcystin, methyl-microcystin were identified in the laboratory simulated water of the mixture of MC-LR and liquid chlorine in the mass ratio of 1∶10. Conclusion: The established MC-LR detection method can be well applied to the monitoring of MC-LR in drinking water due to its simple pre-treatment process and good methodological validation parameters. The degradation products of treatment processes was different.

Characterization of the NLRC5 promoter in chicken: SNPs, regulatory elements and CpG islands.

NLRC5 plays an important role in the innate immunity and cellular immunity in many species, but the regulatory mechanism of NLRC5 expression in chickens remains unclear. In this study, a series of deletion fragments of the NLRC5 promoter region were constructed and dual-luciferase assay was performed. Then, we detected the SNP in the core region and its function. Important transcriptional regulatory elements were predicted and identified. Methylation of CpG islands was measured. The results revealed that the two core regions of -4372 to -3756 and -2925 to -2265 in the NLRC5 promoter were essential for NLRC5 mRNA expression in which a SNP (A/G), located at -2470, was found to have an effect on the transcriptional activity. Also, the STAT1 element in the second core region of the NLRC5 promoter was identified to bind with the STAT1 transcription factor, which was necessary for the transcriptional activity. In addition, many other elements in the NLRC5 promoter, including YY1 and CEBP, may contribute significantly to the expression activity of NLRC5. Moreover, two CpG islands were searched. Part of one was located in the first core region, which suggests that epigenetic modification may regulate the activity of the first promoter region, and the other was mostly in an unmethylated state. Collectively, these results suggest the complex regulation of NLRC5 expression includes SNPs, transcription factors and methylation.

A novel micro-tensile system for full-field deformation measurement of thin films.

We propose a novel micro-tensile system fit for mechanical property characterization of low-dimensional materials. The micro-tensile system was integrated with a micro-tensile apparatus driven by a piezoelectric transducer (PZT) and an optical microscope. The displacement provided by the PZT actuator was amplified by a lever structure on the micro-tensile apparatus. A stalloy was designed to transmit the displacement and reduce the mechanical resistance to the PZT actuator. Quantitative analysis was conducted for the designed apparatus. A calibration experiment was performed based on the micro-scale digital image correlation under the optical microscope. To validate the feasibility, the PET film specimen with a V-notch was tested by the proposed system. The results indicate that the proposed micro-tensile system is reliable and powerful.

[Air pollution and adverse birth outcome in China: a comprehensive review].

Objective: To summarize the progress in the research of the association between air pollution and adverse birth outcomes in China. Methods: A literature retrieval was conducted by using the databases of CNKI, Wanfang, Pubmed, Science Direct, and Web of Science to select relevant research papers published before 30(th), June 2016 in China according to inclusion criteria. Finally, 27 papers were included in analysis. Results: Exposure to particulate matter (PM(10)), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), total suspended particles (TSP) during pregnancy might increase risk for low birth weight; exposure to PM(10), SO(2), NO(2) during pregnancy might increase risk for premature birth; and exposure to SO(2), NO(2), ozone (O(3)), and PM(10) during pregnancy might increase risk for congenital heart diseases and other birth defects. Conclusion: Exposure to air pollutants during pregnancy might increase the risk for adverse birth outcomes, and further studies are needed to prove the association.

Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

OBJECTIVE: Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a ß-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. MATERIALS AND METHODS: Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. RESULTS: Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. CONCLUSIONS: Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

Effect of hemorrhagic shock on endotoxin-inducing TNF production and intra-tissue lipopolysaccharide-binding protein mRNA expression and their relationship.

In order to further elucidate effect of hemorrhagic shock on endotoxin-inducing cytokine production, the present study was designed to investigate the production of tumor necrosis factor alpha (TNF alpha) induced by low-dose (1 microgram/kg) of lipopolysaccharide (LPS) and its cellular sources after hemorrhagic shock (HS) in rats. With combination of expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs, and kidneys, we further analyzed a possible mechanism for increasing sensitivity to LPS by shock. We found in vivo that plasma TNF alpha levels in the HS + LPS group were 20-fold higher than those in the HS group (p < .01) and 2.7-fold higher than those in the LPS group (p < .05). It was shown in vitro that the capacity of the peripheral white blood cells to produce TNF alpha in response to LPS stimulation was significantly decreased by 126% (p < .01) and 57% (p < .05) compared with the pre-shock levels and sham group, respectively, at the end of resuscitation following shock, and still markedly inhibited 3 h after resuscitation, while the capacity of hepatic Kupffer's cells to produce TNF alpha was significantly increased by 110% compared with the sham group (p < .01) after shock and resuscitation. Results from RT-PCR showed that expression of LBP mRNA in the liver, lungs, and kidneys was increased after shock and resuscitation. It is suggested that hemorrhagic shock could significantly strengthen endotoxin to induce TNF alpha production, which might be due to up-regulation of LBP expression in tissues after shock, and the tissue macrophage population may be the main source for cytokine production in shock.

Ultrashort electron pulses as a four-dimensional diagnosis of plasma dynamics.

We report an ultrafast electron imaging system for real-time examination of ultrafast plasma dynamics in four dimensions. It consists of a femtosecond pulsed electron gun and a two-dimensional single electron detector. The device has an unprecedented capability of acquiring a high-quality shadowgraph image with a single ultrashort electron pulse, thus permitting the measurement of irreversible processes using a single-shot scheme. In a prototype experiment of laser-induced plasma of a metal target under moderate pump intensity, we demonstrated its unique capability of acquiring high-quality shadowgraph images on a micron scale with a-few-picosecond time resolution.

[Early fluid therapy for dogs with severe burn-blast combined injury].

Fifty male mongrel dogs were inflicted with 25% III degree burn combined with moderate blast injury. They were divided into five groups; four treatment groups (with various amounts of infused fluid and sodium) and one control group. Each group consisted of 10 animals. The results indicated that every kind of treatment was effective. However, the regime of crystalloid plus whole blood (infused 8 h after injury) was the best. Generally speaking, fluid therapy should be given carefully. The optimal amount of sodium given was 0.3 mmol.kg-1.1%.BSA-1. The amount of water-2-2.5ml.kg-1% BSA-1. After treatment with the Parkland formula, the pulmonary water content was high, so it is not worth recommending. Continuous measurement of the viscosity of plasma, microhematocrit and the amount of sodium in urine and blood were simple and useful.

Immune responses, and autoimmune outcome, during virus infection of the central nervous system.

A combined role of a virus infection of the central nervous system (CNS) and an autoimmune response to myelin basic protein (MBP), an autoantigen of the CNS, is suggested in the pathogenesis of multiple sclerosis (MS). SJL mice are highly susceptible while B6 mice are less susceptible to the induction of experimental autoimmune encephalomyelitis (EAE), the autoimmune model of MS. Peripheral inoculation of Semliki forest virus (SFV) into SJL and B6 mice resulted in: (1) Higher viral titers, more severe clinical disease, and hence a stronger nonspecific and SFV-specific lymphoproliferation, and production of IFN-gamma and TNF/LT was observed by splenocytes (SPL) of B6 than by those of SJL mice, on Day 7 postinfection. (2) Following viral clearance, however, proliferation to SFV, and to MBP, and the production of IFN-gamma and TNF/LT by SPL of SFV-infected SJL mice were significantly higher, while the production of TGF-beta was significantly lower than by those of B6 mice. In conclusion, the immune responses to SFV, and to MBP, which were triggered by SFV infection were significantly higher and more prolonged in the SPL of SJL mice, the EAE-susceptible mice, than by those of B6 mice after the infection was cleared.

Effects of excitatory amino acids and nimodipine on calcium currents in cultured rat cortical neurons.

AIM: To study the effect of excitatory amino acid (EAA) and calcium channel blocker on neuronal calcium channels. METHODS: With path-clamp technique (whole-cell recording), the effects of Bay-K-8644, cesium glutamate, potassium aspartate, and nimodipine (Nim) on calcium currents (ICa) in cultured cortical neurons of neonatal rats were studied. RESULTS: ICa was raised obviously by Bay-K-8644 and glutamate. ICa was raised concentration-dependently by aspartate (0.5, 5, 50 mmol.L-1), with increasing rates 15% +/- 3%, 37% +/- 3%, and 53% +/- 6%, respectively. The inhibition of ICa was obvious while adding Nim in the bath solution. With Nim 10 mumol.L-1, the inhibitory rate was 46% +/- 4%. CONCLUSION: EAA had increasing effects on neuronal calcium currents and Nim inhibited Ca2+ influx in neurons.

Plasma cytokines and endotoxin levels in patients with severe injury and their relationship with organ damage.

In 17 patients plasma TNF-alpha and IL-8 were assayed with enzyme-linked immunosorbent assay. IL-6 activity in plasma was determined by bioassay with IL-6-dependent cell line 7TD1. The limulus amoebocyte lysate chromogenic test was used for plasma endotoxin assay. Plasma cytokine levels in injured patients were significantly increased. Plasma TNF-alpha was shown to be increased earlier, while an increase in plasma IL-6 and IL-8 levels occurred late, all of which were shown to be significantly positively correlated with ISS, cardiac and hepatic enzyme activities, and index of renal function. In addition, obvious endotoxaemia occurred at an early stage of injuries, which was respectively significantly correlated with ISS and plasma TNF-alpha, IL-6 and IL-8 levels. Severe injuries could induce increased successive release of TNF-alpha, IL-6 and IL-8, and obvious endotoxaemia. The post injury release of cytokines might be related to endotoxaemia, and may play an important role in the development of organ damage after injury.

Dynamic changes of lung lymph flow and the release of lysosomal enzyme from the lungs after severe steam inhalation injury in goats.

Chronic lung lymph fistulae were produced in six goats according to Winn's and Stothert's methods with our modification to define the pathophysiology of pulmonary oedema after severe steam inhalation injury. Arterial blood gas, lung lymph flow (QLym), lymph/plasma total protein concentration ratio (L/P), and beta-glucuronidase (beta-G) in plasma and lung lymph were monitored for 24 h post-injury. The pathological changes in the lung tissues were also determined at the end of the study. It was found that directly after injury, QLym increased steadily to a peak value at 6 h, followed by declining values at 18 and 24 h. L/P decreased promptly during the 60 min after injury and then also steadily increased to a peak value at 4 h (P less than 0.05). A significant increase in plasma beta-G was only observed at 4 h post-burn. However, lung lymph beta-G activities and lymph beta-G transport increased immediately after injury, reaching a peak at 4 h (5 and 12 times above baseline values, respectively, P less than 0.01). Significant hypoxaemia and hypocapnia occurred at 2 h post-burn and deteriorated progressively throughout the study. There were obvious pulmonary interstitial and alveolar oedema microscopically. This study demonstrates that the increase in transvascular fluid and protein flux after steam inhalation injury is mainly due to increased pulmonary microvascular permeability. Nevertheless, a hydrostatic pressure effect can not be completely excluded, especially in the first hour post-burn. Lysosomal enzyme release is considered to be one of the important factors which damage lung microvascular elements and induce an increase in their permeability.

Blood gas studies in dogs with severe steam inhalation injury.

The dynamic changes in blood gases in 34 dogs suffering severe steam inhalation injury were studied during the first 14 days post-burn to determine the effects of inhalation injury on lung function. Nineteen dogs received only severe steam inhalation injury, while 15 other dogs received both 30 per cent total body surface area (TBSA) deep burns and steam inhalation injury. The results showed marked reductions of PaO2, PaCO2, AB, SBE, T-CO2, SB, BBp, pHNR and SatO2 (P less than 0.05 approximately 0.01), whereas the P(A-a)O2 increased (P less than 0.05 approximately 0.01) within week 1 post-burn in both groups. These data suggest that the injured animals were suffering from hypoxaemia and respiratory alkalosis induced by disturbance of the gas-exchange function of the lungs. There was also metabolic acidosis, which was closely related to high fever, excessive catabolism, and particularly to hypoxaemia in week 1 post-burn. If the animals survived through the critical period (1-7 days post-burn), most of the abnormal gas parameters then gradually returned to the pre-burn levels. It is clear, therefore, that blood gas monitoring in patients with inhalation injury is not only of diagnostic importance but also of prognostic value.