Cost-effectiveness evaluation of different control strategies for Clonorchis sinensis infection in a high endemic area of China: A modelling study

Clonorchiasis is an important food-borne parasitic disease caused by Clonorchis sinensis infection. The evaluation of long-term cost-effectiveness of control strategies is important for disease control and prevention. The present study aimed to assess the cost-effectiveness of the three recommended strategies (i.e., WHO, Chinese and Guangdong strategies) and different combinations of commonly used measures (i.e., preventive chemotherapy, information, education, and communication (IEC) and environmental improvement) on clonorchiasis. The study area, Fusha town in Guangdong Province, was a typical high endemic area in China. The analysis was based on a multi-group transmission model of C. sinensis infection. We set the intervention duration for 10 years and post-intervention period for 50 years. The corresponding costs and DALYs were estimated. Strategies with incremental cost-effectiveness ratios (ICERs) less than 1/5 of the willingness-to-pay threshold were identified as highly cost-effective strategies. The optimal control strategy was obtained using the next best comparator method. The ICERs of Guangdong strategy were $172 (95% CI: $143-$230) US for praziquantel and $106 (95% CI: $85-$143) US for albendazole, suggesting the highest cost-effectiveness among the three recommended strategies. For praziquantel, 470 sets of control strategies were identified as highly cost-effective strategies for achieving infection control (prevalence<5%). The optimal strategy consisted of chemotherapy targeted on at-risk population, IEC and environmental improvement, with coverages all being 100%, and with the ICER of $202 (95% CI: $168-$271) US. The results for transmission control (prevalence<1%) and albendazole were obtained with the same procedures. The findings may help to develop control policies for C. sinensis infection in high endemic areas. Moreover, the method adopted is applicable for assessment of optimal strategies in other endemic areas.     

Genetic validation of Aspergillus fumigatus phosphoglucomutase as a viable therapeutic target in invasive aspergillosis

Aspergillus fumigatus is the causative agent of invasive aspergillosis, an infection with mortality rates of up to 50%. The glucan-rich cell wall of A. fumigatus is a protective structure that is absent from human cells and is a potential target for antifungal treatments. Glucan is synthesized from the donor uridine diphosphate glucose, with the conversion of glucose-6-phosphate to glucose-1-phosphate by the enzyme phosphoglucomutase (PGM) representing a key step in its biosynthesis. Here, we explore the possibility of selectively targeting A. fumigatus PGM (AfPGM) as an antifungal treatment strategy. Using a promoter replacement strategy, we constructed a conditional pgm mutant and revealed that pgm is required for A. fumigatus growth and cell wall integrity. In addition, using a fragment screen, we identified the thiol-reactive compound isothiazolone fragment of PGM as targeting a cysteine residue not conserved in the human ortholog. Furthermore, through scaffold exploration, we synthesized a para-aryl derivative (ISFP10) and demonstrated that it inhibits AfPGM with an IC₅₀ of 2 μM and exhibits 50-fold selectivity over the human enzyme. Taken together, our data provide genetic validation of PGM as a therapeutic target and suggest new avenues for inhibiting AfPGM using covalent inhibitors that could serve as tools for chemical validation.     

17β‐Oestradiol facilitates M2 macrophage skewing and ameliorates arrhythmias in ovariectomized female infarcted rats

Epidemiological studies have suggested a lower incidence of arrhythmia‐induced sudden cardiac death in women than in men. 17β‐oestradiol (E2) has been reported to have a post‐myocardial infarction antiarrhythmic effect, although the mechanisms have yet to be elucidated. We investigated whether E2‐mediated antioxidation regulates macrophage polarization and affects cardiac sympathetic reinnervation in rats after MI. Ovariectomized Wistar rats were randomly assigned to placebo pellets, E2 treatment, or E2 treatment +3‐morpholinosydnonimine (a peroxynitrite generator) and followed for 4 weeks. The infarct sizes were similar among the infarcted groups. At Day 3 after infarction, post‐infarction was associated with increased superoxide levels, which were inhibited by administering E2. E2 significantly increased myocardial IL‐10 levels and the percentage of regulatory M2 macrophages compared with the ovariectomized infarcted alone group as assessed by immunohistochemical staining, Western blot and RT‐PCR. Nerve growth factor colocalized with both M1 and M2 macrophages at the magnitude significantly higher in M1 compared with M2. At Day 28 after infarction, E2 was associated with attenuated myocardial norepinephrine levels and sympathetic hyperinnervation. These effects of E2 were functionally translated in inhibiting fatal arrhythmias. The beneficial effect of E2 on macrophage polarization and sympathetic hyperinnervation was abolished by 3‐morpholinosydnonimine. Our results indicated that E2 polarized macrophages into the M2 phenotype by inhibiting the superoxide pathway, leading to attenuated nerve growth factor‐induced sympathetic hyperinnervation after myocardial infarction.     

祁连山典型流域谷地植被斑块演变与土壤性状

植物群落演变与土壤性状变化之间的相互作用和过程研究对于认识生态系统结构和功能演变有着重要的意义.对祁连山谷地灌丛草甸退化演变过程中植物群落物种组成、土壤物理和化学性状特征、及土壤与植被的相互作用进行了研究,结果表明,在祁连山谷地阴坡林线以下较小的空间范围,植被斑块由金露梅群落向金露梅-马蔺群落斑块和马蔺群落斑块演变,植被盖度降低,但物种多样性增加.不同植被斑块之间土壤水分有显著的梯度变化,土壤水分的变化导致植被的退化演替.植被斑块的演变导致土壤性状的明显分异,从金露梅灌丛斑块向金露梅-马蔺群落斑块和马蔺群落斑块演变,土壤容重显著增加,土壤团聚体组成由大粒级的大团聚体(》1mm)破碎为小粒级的大团聚体(1-0.25mm)和微团聚体(《0.25mm),团聚体稳定性降低,表明土壤结构的退化;土壤有机碳含量下降了31.2%和55.9%,干筛各粒级土壤团聚体中有机碳含量金露梅-马蔺群落斑块和马蔺群落斑块显著低于金露梅斑块,土壤团聚体平均重量粒径与有机碳含量存在显著相关,植被退化演变中土壤有机碳的损失部分地由于团聚体的破碎引起;土壤全氮和有效氮不同斑块之间也有显著的差异,植被斑块退化演变使氮的有效性降低;但磷、钾养分对植被变化的响应不敏感.植被的退化演变使土壤团聚体破碎、土壤结构退化,有机碳和全氮含量下降,使其抗侵蚀能力和水源涵养功能显著降低,又进一步加速植被的退化演替.在气候变暖的趋势下,马蔺斑块将进一步向林线逼近,灌丛草甸植被将会进一步退化和萎缩.     

Hemin with Peroxidase Activity Can Inhibit the Oxidative Damage Induced by Ultraviolet A

Excessive reactive oxygen species (ROS), a highly reactive substance that contains oxygen, induced by ultraviolet A (UVA) cause oxidative damage to skin. We confirmed that hemin can catalyze the reaction of tyrosine (Tyr) and hydrogen peroxide (H₂O₂). Catalysis was found to effectively reduce or eliminate oxidative damage to cells induced by H₂O₂ or UVA. The scavenging effects of hemin for other free-radical ROS were also evaluated through pyrogallol autoxidation, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)-scavenging assays, and phenanthroline–Fe²⁺ assays. The results show that a mixture of hemin and tyrosine exhibits strong scavenging activities for H₂O₂, superoxide anion (O₂⁻·), DPPH·, and the hydroxyl radical (·OH). Furthermore, the inhibition of oxidative damage to human skin keratinocyte (HaCaT) cells induced by H₂O₂ or UVA was evaluated. The results show that catalysis can significantly reduce the ratio of cell apoptosis and death and inhibit the release of lactate dehydrogenase (LDH), as well as accumulation of malondialdehyde (MDA). Furthermore, the resistance to apoptosis was found to be enhanced. These results show that the mixture of hemin and tyrosine has a significantly protective effect against oxidative damage to HaCaT cells caused by UVA, suggesting it as a protective agent for combating UVA damage.     

蒲洼农业生态系统能流的稳定性及其动态

在研究生态系统结构及功能的基础上,本文基于１９７５－１９９０年的数据,对蒲洼农业生态系统能流的稳定性及其动态进行了分析。通过建立能流模型,由李雅普诺夫稳定性原理,得出该生态系统能流的平衡态具有渐近稳定性。动态数学模拟表明,目前该系统的能量流动正从不稳定状态向稳定和平衡态过渡,这一过程大约需要７ａ时间。     

Studying Early Nodulin Gene ENOD40 Expression and Induction by Nodulation Factor and Cytokinin in Transgenic Alfalfa

ENOD40, an early nodulin gene, is expressed following inoculation with Rhizobium meliloti or by adding R. meliloti-produced nodulation (Nod) factors or the plant hormone cytokinin to uninoculated roots. We isolated two MsENOD40 clones, designated MsENOD40–1 and MsENOD40–2, with distinct promoters from an alfalfa (Medicago sativa cv Chief) genomic library. The promoters were fused to the reporter gene uidA (gus), and the constructs were introduced into alfalfa. We observed that the MsENOD40–1 construct was expressed almost exclusively under symbiotic conditions. The MsENOD40–2 construct was transcribed under both symbiotic and nonsymbiotic conditions and in nonnodular and nodular tissues. Both MsENOD40 promoter-gus constructs were similarly expressed as nodules developed, and both were expressed in roots treated with 6-benzylaminopurine or purified Nod factor. However, no blue color was detected in nodule-like structures induced by the auxin transport inhibitor N-1-(naphthyl)phthalamic acid on roots of plants containing the MsENOD40–1 promoter construct, whereas pseudonodules from plants containing the MsENOD40–2 promoter construct stained blue. A 616-bp region at the distal 5′ end of the promoter is important for proper spatial expression of MsENOD40 in nodules and also for Nod-factor and cytokinin-induced expression.     

Aerobic denitrification by novel isolated strain using NO-₂-N as nitrogen source

Biological denitrification reaction can be achieved under aerobic environment. Few aerobic denitrifiers using nitrite as sole nitrogen source were identified. Using nitrite as the sole nitrogen source, this work assessed the denitrification activity of yy7, an aerobic heterotrophic denitrifier identified as Pseudomonas sp. (94% similarity) by 16S rRNA sequencing analysis. The logistic equation describes the cell growth curve, yielding a generation time of 2.9h at an initial 18 mg l(-1)NO(-)?-N. Reduction of NO(-)?-N was primarily achieved during its logarithmic growth phase, and was accompanied by an increase in suspension pH and near complete consumption of dissolved oxygen. Three genes relating to nirK, norB, and nosZ were noted to involve in isolate strain. Isolate yy7 can survive and remove up to 40 mg l(-1)NO(-)?-N and, hence, can be applied as an effective aerobic denitrifier during simultaneous nitrification and denitrification via nitrite processes.     

330例2型糖尿病患者死因分析

目的:通过对80年代、90年代及近6年(2000-2006)我院2型糖尿病患者死因的比较,探讨分析糖尿病患者的死亡原因及其变迁,为提高糖尿病防治水平,减少糖尿病死亡率提供科学依据。方法:采用回顾性调查方法对我院1983-2006年住院2型糖尿病患者死因进行分析,并分三阶段进行比较。共调查2型糖尿病死亡病例330例。结果:不同年代心脑血管疾病均是导致2型糖尿病患者死亡的主要原因,位居死因第一,占总死亡人数的38.2%。肿瘤作为2型糖尿病患者的死因所占比例明显增加,占总死亡人数的19.4%。以感染为直接死因逐渐下降,但仍为重要死因,占14.2%。而糖尿病酮症酸中毒、高渗昏迷和低血糖昏迷等急性并发症所占比例显著减少,占8.8%。结论:糖尿病慢性并发症尤其是心脑血管病变是2型糖尿病的主要死因,近年来肿瘤已经成为2型糖尿病患者的重要死因,以感染为直接死因逐渐下降,但仍为重要死因,而糖尿病酮症酸中毒、高渗昏迷和低血糖昏迷等急性并发症所占比例显著减少。