脓毒症休克血管低反应性机制及临床对策

脓毒症休克依然是严重创伤、大面积烧伤等危重患者最常见并发症和死亡原因之一。尽管脓毒症患者血浆儿茶酚胺水平升高、肾素一血管紧张素系统高度激活，但是许多患者对液体复苏和血管活性药物治疗效果不佳，出现非常棘手的顽固性低血压。其原因与内毒素诱导血管内皮细胞（VEC）功能损伤、全身微血管舒缩功能紊乱，进而导致血管低反应性、甚至血管麻痹性舒张等病理生理过程有关。笔者就如何针对血管低反应性的机制来选择适当的治疗措施进行探讨。

Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease

AIM： To assess whether treatment with insulinsensitizing agents （ISAs） in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet （MCDD） rat model of non-alcoholic fatty liver disease （NAFLD）. METHODS： Rats （n = 6 per group） were treated with different drugs, including MCDD only, MCDD diet with either metformin （200 mg/kg）, rosiglitazone （3 mg/kg）, metformin plus rosiglitazone （M＋R）, ezetimibe （2 mg/ kg）, valsartan （2 mg/kg）, or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured. RESULTS： Fatty liver （FL） rats demonstrated severe hepatic fatty infiltration （〉 91% fat）, with an increase in hepatic TG （＋1263%, P 〈 0.001）, hepatic cholesterol （＋245%, P 〈 0.03）, hepatic MDA levels （＋225%, P 〈 0.001）, serum TNF-alpha （17.8 ＋ 10 vs 7.8 ＋ 0.0, P 〈 0.001）, but a decrease in hepatic alpha tocopherol （-74%, P 〈 0.001） as compared to the control rats. Combination therapy with all drugs produced a significant decrease in liver steatosis （-54%）, hepatic TG （-64%）, hepatic cholesterol （-31%） and hepatic MDA （-70%）, but increased hepatic alpha tocopherol （＋443%） as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis （-32% vs -54%, P 〈 0.001） and in hepatic MDA levels （-55% vs -70%, P 〈 0.01）, but a similar decrease in hepatic lipids when compared with the all drugs combination. TNF-alpha levels decreased significantly in all treatment groups except in ISA group. CONCLUSION： Combination therapies have a greater effect on liver fat content as compared to monotherapy. Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin.

Transboundary water vulnerability and its drivers in China

Competitive use of transboundary freshwater resources is becoming one of the key factors influencing regional peace and political relationship among states.In China, 18 major international river basins are concentrated in three regions, of which the total annual outflow at the border is 7320×108 m3, occupying 26.8% of the total annual runoff of China, and the inflow at the border is only 172×108 m3.In this paper, we analyzed the major drivers affecting shared water vulnerability in China, namely:(1) changes in physical conditions affecting the availability of water;(2) competing objectives between economic development and ecological conservation;(3) lack of emergency response mechanisms;(4) unsound administrative institutions;and(5) shortcomings in the development of regional cooperation based on transboundary waters.We concluded by identifying four pathways for reducing vulnerability:(1) encouraging scientific research cooperation;(2) constructing information-sharing channels;(3) establishing early-warning mechanisms;and(4) promoting further coordination and negotia-tion.

Inhibition mechanism between sodium(Na3AlF6)and sulfur on coke reactivity

Inhibition mechanism between sodium （NaaAlF6） and sulfur on coke reactivity was investigated by simulating petroleum coke with low-impurity pitch coke and by impurity doping. The mechanism was discussed by scanning electron microscopy, energy-dispersive spectrometry, and X-ray powder diffraction. Results show that Na effectively inhibited S catalysis during carbon-air/CO2 reactions, and S inhibited the catalysis of Na during carbon- air reaction to a certain extent. A stable structure with a Na-to-S atomic ratio of 1.4 and a cyclic reaction system of ＂Na2SO3→ Na2S→Na2CO3→ Na2SO3＂ were likely the keys to producing this mutual inhibition.

Biochemical response to lamivudine treatment in HBeAg negative chronic hepatitis B patients in Iran

AIM： To study the effect of a one-year lamivudine regimen in patients with chronic hepatitis B. METHODS： Medical records of HBeAg negative hepatitis B patients who attended a hepatitis clinic in Tehran between March 2002-March 2004 were evaluated. The patients received 100 mg lamivudine tablets once daily for at least 12 mo. Liver enzymes and complete blood count were checked at baseline and the end of treatment （12th mo） and 6 mo after discontinuation of treatment. RESULTS： Of all patients, 24 were excluded. Of 71 patients left, 58 （81.7%） were men. Mean age of the patients was 38 ± 14 years. Mean level of ALT in serum was 1437 ± 205 nkat/L at baseline with a significant reduction at the end of treatment to a mean level of 723 ± 92 nkat/L （P = 0.002）. In 38 patients （53.5%）, the ALT level was normal after one-year treatment. Five patients （7.3%） relapsed （biochemically） within 6 mo after discontinuing lamivudine therapy （the patients with good end of treatment response）. Mean level of AST in serum was 1060 ± 105 nkat/L at baseline which decreased significantly to 652 ± 75 nkat/L at the end of treatment （P = 0.002）. CONCLUSION： Over half （53.5%） of chronic hepatitis B patients with HBeAg negative have normal liver enzyme level at 12-mo lamivudine therapy.

Dissolution kinetics of kaolin mineral in acidic media for predicting optimal condition for alum production

The dissolution kinetics and mechanisms of reaction of Batagbon Kaolin in sulphuric and fluosilicic acids were studied. Leaching temperature, acid concentration, particle size, solid-to-liquid ratio, and stirring speed were selected as process parameters. It is observed that the dissolution rate increases with decreasing particle size and solid-to-liquid ratio, and increases with stirring speed, acid concentration, and leaching temperature. The experimental results indicate that the dissolution rate is of mixed control via hydrogen ion [H＋] action, with reaction order of 0.813 and the reaction kinetics can be expressed as gmt=[1-（1-x）l/3＋y/6[（l-x）l/3＋ 1-2（1-x）2/3]. The activation energy of the process is determined to be 21.6 k J/mol. The level of the product quality is also evaluated.

REFLUX ESOPHAGITIS AND AIRWAY HYPERRESPONSIVENESS

Objectives’ To observe the effects of reflux esophagitis(RE) on the lung function and alrway reactivity,and study the mechanism of airway hyperresponsiveness(AHR) in patients with RE.Methods. Lung function measurements and airway provocation tests were performed in 31 RE patientsand 35 control subjects’ TXB, and PGF,. were determined in 20 cases of each group.Results. In RE patients the lung function was lower and the rate of AHR was higher than control sub-jects (P<0. 05). Among RE patients 25 % had higher airway sensitivity (Dminr 3u ). The TXB2 of REpatients with AHR was higher than those without AHR’ Dmin correlated significantly with TXB2 (r=0. 653, P<0. 05).Concluswhs’ RE could damage the lung function. The rate of AHR was 61 %, the high airway sensltivity was probably potential asthma, and TXB2 may play a role in the pathogenesis of AHR.

Mechanism of Immune Hyporesponsiveness Induced by Recipientderived Immature Dendritic Cells in Rat Liver Transplantation

Objective： The use of donor-derived immature dendritic cells （imDC） has become a promising approach to induce immune tolerance or immune hyporesponsiveness. However, donor-derived imDC needs to be harvested for a few days and transfused into the recipient in 5-10 days before transplantation, which is practically impossible in a clinical setting where donor organs are mainly harvested from cadavers. Moreover, donor-derived imDC might be cleared by allogeneic reaction offsetting induced immune tolerance or immune hyporesponsiveness. In our study, we further explored the underlying mechanism of immune hyporesponsiveness induced by donor-antigen-unloaded recipient-derived imDC by transfusing these imDC into rats in 1 day before liver transplantation. This paper is to study the mechanism of immune hyporesponsiveness induced by donor-antigen-unloaded recipient-derived imDC and its protection of liver grafts in rats. Methods： 40 SD rats （donor） and 40 male Wistar rats （recipient） were randomly divided into 4 groups： control, cyclosporine A （CsA）, mature DC （mDC）, and imDC; with 10 SD rats and 10 Wistar rats for each group. Animal models of acute graft rejection were established with these rats. Corresponding treatments were given before or after transplantation. In the control group, Wistar rats received no treatment other than liver transplantation. In the CsA group, Wistar rats underwent liver transplantation plus CsA treatment （10 mg/kg·d） in the starting day 2 after transplantation. For the mDC group, recipient-derived mDC （1 × 10^6/rat） were infused intravenously via the dorsal vein of the penis to recipient rats. For the imDC group, imDC （1× 10^6/rat） were injected into recipient rats via the dorsal vein of the penis. In each group, 5 recipients were executed at 10 days after transplantation; the remaining five recipients were kept for the observation of survival time. Blood samples were collected for the measurement of ALT and TBIL; IL-2, IFN-γ, IL-4 and IL-10 and levels were measured with double-antibody sandwich ELISA. Liver tissue was harvested for HE staining and the observation of histological features. Acute rejection was evaluated with Banff classification. Expression levels of Fas-L/Fas in the grafts were detected by iminunohistochemieal staining; and western blot was used to detect the expression level of Scurfin. Results： The median survival times （MST） of the liver allografls in the CsA and imDC group were significantly longer than those in the control or mDC group （P〈0.05）. The serum levels of ALT and TBIL in the control and mDC groups were significantly higher than those of the CsA or imDC group （P〈0.05）. Compared with the CsA anti imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower than those of the control and mDC groups （P〈0.01）. Slight or no rejection reaction was found in the CsA anti imDC groups （P〈0.05）. The expression level of Scurfin protein in CD4^＋ CD25^＋ T cells of the imDC group was significantly higher than that of three other groups （P〈 0.05）. Conclusion： Donor-antigen-unloaded recipient- derived imDC is an effective treatment in inducing immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span was significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced hy imDC transfusion may involve the preprocesses of T cell apoptosis induction, immune tolerance or hyporesponsiveness in T cells, induction of the shift in TH1/TH2 balance, selection activation of Th2 subset, or induction of regulatory T cell.

Exploration of structure and mechanism of insoluble gels formed in microwave-assisted Suzuki coupling for poly(9,9-dihexylfluorene)s

A series of poly(9,9-dihexylfluorene)s (PDHFs) have been synthesized via microwave-assisted Suzuki and Yamamoto coupling reactions. Compared with the conventional oil-bath heating (48 h, Mw 20100 g/mol by Suzuki reaction and Mw 24000 g/mol by Yamamoto reaction), microwave-assisted polymerization can yield PDHFs with higher molecular weights (Mw 37200 g/mol by Suzuki reaction and Mw 43400 g/mol by Yamamoto reaction) in shorter time (14 and 60 min). However, sometimes formation of insoluble gels was observed together with PDHF in Suzuki coupling reaction. PDHF and insoluble gels were analyzed by XPS, elemental analysis, FTIR, TGA and DSC. Experimental results demonstrated that H2O might take part in the Suzuki coupling reaction under microwave condition, which could make the cross-linking reaction occur and form gels.

Nanosurface chemistry and dose govern the bioaccumulation and toxicity of carbon nanotubes, metal nanomaterials and quantum dots in vivo

The chemical and biological mechanisms of life processes mostly consist of multistep and programmed processes at nanoscale levels. Interestingly enough, cell, the basic functional unit and platform that maintains life processes, is composed of various organelles fulfilling sophisticated functions through the precise control on the biomolecules （e.g., proteins, phospholipid, nucleic acid and ions） in a spatial dimension of nanoscale sizes. Thus, understanding of the activities of manufactured nanoscale materials including their interaction with biological sys- tems is of great significance in chemistry, materials sci- ence, life science, medicine, environmental science and toxicology. In this brief review, we summarized the recent advances in nanotoxicological chemistry through the dis- section of pivotal factors （primarily focusing on dose and nanosurface chemistry） in determining nanomaterial- induced biological/toxic responses with particular empha- sis on the nanomaterial bioaccumulation （and interaction organs or target organs） at intact animal level. Due to the volume of manufacture and material application, we deliberately discussed carbon nanotubes, metal/metal oxide nanomaterials and quantum dots, severing as representativematerial types to illustrate the impact of dose and nanosurface chemistry in these toxicological scenarios. Finally, we have also delineated the grand challenges in this field in a conceptual framework of nanotoxicological chemistry. It is noted that this review is a part of our persistent endeavor of building the systematic knowledge framework for toxicological properties of engineered nanomaterials.

Effects of phospholipase D on cardiopulmonary bypass-induced neutrophil priming

Objective:To investigate the relationship betwe en phospholipase D (PLD) activation and neutrophil priming induced by cardiopulm onary bypass (CPB), and try to clarify whether CPB-induced systemic inflammator y response can be attenuated by inhibiting neutrophilic PLD activation. Methods:Neutrophils were isolated from arterial blood of 8 pat ients undergoing valve replacement before operation and 30 min after initiation of CPB respectively. Both the preoperative and CPB-stirred neutrophils were sub divided into 5 groups by receiving different experimental interventions: (1) bac terial lipopolysaccharide (LPS, 10 ng·ml -1 ), (2) N-formylmethionylph enylalanine (fMLP, 1 μmol·L -1 ), (3) LPS+fMLP, (4) 1-butanol ( 0.5 %)+ LPS+fMLP, (5) vehicle. Elastase and myeloperoxidase (MPO) release was measured f or the parameters of neutrophil activation, neutrophil PLD activity was determin ed by quantitation of choline produced from the stable product of phosphatidylch oline catalyzed by PLD. Results:(1) Preoperative neutrophils treated with LPS+fMLP pre sented significantly higher PLD activity ( 13.48 ± 2.61 nmol choline·h -1 ·mg -1 ) and released more elastase and MPO than cells treated with v ehicle (PLD activity 3.70 ± 0.49 nmol choline·h -1 ·mg -1 , P< 0.01 ), LPS (P< 0.01 ) and fMLP respectively. In 1-butanol+LPS+fMLP group, PLD activity of preoperative neutrop hils was lower than that in LPS+fMLP group (P< 0.01 ), b esides the release of elastase and MPO decreased sharply below both LPS + fMLP a nd fMLP groups (P< 0.01 ). In LPS group, PLD activity wa s higher (P< 0.01 ), while elastase and MPO release did not differ from control. fMLP group presented PLD activity, elastase and MPO rel ease higher than control (P< 0.01 ); nevertheless, lower than LPS+fMLP group (P< 0.01 ). (2) CPB-stirred neutro phils presented prominent PLD activity increment, and even the control level was 3.59 -fold of the pre-operative control (P< 0.01 ) . PLD activity in LPS+fMLP group was higher than that in other groups. Notably, PLD activity was even nonstatistically lower in 1-butanol+LPS+fMLP group than t hat in LPS or fMLP group. CPB-stirred neutrophils in LPS+fMLP group released mo re elastase and MPO than control, LPS, and 1-butanol+LPS+fMLP groups did ( P< 0.01 ); however, neither of the release was statistically different from that of fMLP group. Conclusions:Cardiopulmonary bypass enables neutrophil priming accompanied with significant increase in PLD activity. Inhibition of neutrophil PLD activation attenuates its priming and may alleviate CPB-induced systemic in flammatory reaction.