Usefulness of intravenous adenosine in idiopathic pulmonary arterial hypertension as a screening agent for identifying long-term responders to calcium channel blockers

Although intravenous adenosine is recommended for acute vasodilator testing in patients with pulmonary hypertension, long-term outcomes in acute responders treated with calcium channel blockers (CCBs) who are identified by adenosine remain unknown. In this study, the value of adenosine for identifying long-term responders to CCBs was investigated in patients with idiopathic pulmonary arterial hypertension (IPAH). All acute responders were subsequently treated with high-dose CCB monotherapy, and 6-minute walk distances, hemodynamic data, and World Health Organization functional classifications were followed. Nine of 104 patients exhibited an acute response with intravenous adenosine (8.7%, 95% confidence interval 3.2 to 14.2). After 12 months of follow-up, all acute responders were still alive; however, only 6 patients showed sustained hemodynamic improvement (5.8%, 95% confidence interval 2 to 13). Three patients had failed CCB monotherapy and bosentan was added to their treatment. Mean tolerated dose of intravenous adenosine was 142 ± 49 μg/kg/min. No life-threatening adverse events were observed and only 2 patients of the nonresponders exhibited a 20% decrease in mean systemic arterial pressure. In nonresponders, 1- and 3-year survival rates were 89% and 75%, respectively. In conclusion, acute vasodilator testing with intravenous adenosine was safe and able to screen responders to CCB therapy in patients with IPAH. Long-term CCB responders accounted for about 5.8% of patients with IPAH.     

Increased expression of ferritin in cerebral cortex after human traumatic brain injury

Despite numerous researches and improvements in the past few years, the precise mechanisms underlying secondary brain injury after trauma remain obscure. Iron is essential for almost all types of cells, including nerve cells. However, excess of iron has been proved to contribute to the brain injury following trauma in animal models. As a key iron-handling protein in the brain, ferritin might be involved in iron-induced pathophysiological process of various brain disorders. Therefore, the current study was aimed to investigate the expression of ferritin in the human contused brain. Nineteen contused brain samples were obtained from 19 patients undergoing surgery for brain contusions 3 h–17 d after trauma, and three normal temporal pole samples from 3 patients with petroclival meningioma were collected as controls. Expression of ferritin-H-chain was measured by quantitative real-time polymerase chain reaction (PCR), western blot and immunohistochemistry, respectively. Perl’s reaction was taken for iron staining. The results showed that human traumatic brain injury (TBI) could up-regulate ferritin-H-chain in pericontusional cortex. A marked increase of ferritin was detected in the early group (≤12 h), and remained elevated for a long time till after 48 h post-injury. The location of ferritin-H-chain was found mainly at the neuron-like cells and seldom at glia-like cells. Perl’s reaction showed that most of the iron-positive cells were glia-like cells. These findings suggested that iron and ferritin might be involved in the secondary brain injury and could be therapeutic targets for patients with TBI.     

脂肪性肝病与胃食管反流病的相关性研究

目的评估脂肪性肝病(FLD)与胃食管反流病GERD之间的关系。方法选取2 000例受试者,采用较简便的胃食管反流病问卷(GerdQ)作为初筛GERD诊断标准,对入选者均进行腹部超声波等检查,分析FLD与GERD关系。结果对2 000例患者利用GerdQ评估GERD诊断情况,有176例(8.8%)诊断为GERD,女68人(38.64%),男108人(61.36%);脂肪肝患者760例,患病率38.0%,在脂肪肝组中,男女性GERD症状的GerdQ阳性率分别为13.77%和12.24%,两者无明显差异(P>0.05)。脂肪肝人群发生GERD症状的患病率与对照组存在统计学差异(P<0.05)。结论脂肪肝与GERD显著相关,控制脂肪肝发展可以降低GERD发病率。     

Enhancing bifunctional catalytic activity of cobalt–nickel sulfide spinel nanocatalysts through transition metal doping and its application in secondary zinc–air batteries

Developing large-scale and high-performance OER (oxygen evolution reaction) and ORR (oxygen reduction reaction) catalysts have been a challenge for commercializing secondary zinc–air batteries. In this work, transition metal-doped cobalt–nickel sulfide spinels are directly produced via a continuous hydrothermal flow synthesis (CHFS) approach. The nanosized cobalt–nickel sulfides are doped with Ag, Fe, Mn, Cr, V, and Ti and evaluated as bifunctional OER and ORR catalyst for Zn–air battery application. Among the doped spinel catalysts, Mn-doped cobalt–nickel sulfides (Ni_1.29Co_1.49Mn_0.22S₄) exhibit the most promising OER and ORR performance, showing an ORR onset potential of 0.9 V vs. RHE and an OER overpotential of 348 mV measured at 10 mA cm⁻², which is attributed to their high surface area, electronic structure of the dopant species, and the synergistic coupling of the dopant species with the active host cations. The dopant ions primarily alter the host cation composition, with the Mn(iii) cation linked to the introduction of active sites by its favourable electronic structure. A power density of 75 mW cm⁻² is achieved at a current density of 140 mA cm⁻² for the zinc–air battery using the manganese-doped catalyst, a 12% improvement over the undoped cobalt–nickel sulfide and superior to that of the battery with a commercial RuO₂ catalyst.

Transition metal-doped cobalt–nickel sulfide spinel (Ni_1.29Co_1.49Mn_0.22S₄) nanocatalysts for secondary Zn–air batteries with an efficient and stable electrochemical performance.     

Aggravation of spinal cord compromise following new osteoporotic vertebral compression fracture prevented by teriparatide in patients with surgical contraindications

Summary

Patients with spinal cord deficits following new unstable osteoporotic compression fracture and surgical contraindications were considered to receive conservative treatment. Teriparatide was better than alendronate at improving bone mineral density and bone turnover parameters, as well as preventing aggravation of spinal cord compromise.

Introduction

This study compared the preventive effects of teriparatide and alendronate on aggravation of spinal cord compromise following new unstable osteoporotic vertebral compression fracture (OVCF) in patients with surgical contraindications.

Methods

This was a 12-month, randomized, open-label study of teriparatide versus alendronate in 49 patients with new unstable OVCF and surgical contraindications. Neurological function was evaluated using modified Japanese Orthopedic Association (mJOA) score (11-point scale, the maximum score of 11 implies normalcy). Visual analog scale (VAS) scores, kyphotic angles, anterior-border heights and diameters of the spinal canal of the fractured vertebrae, any incident of new OVCFs (onset of OVCF during follow-up), spine bone mineral density (BMD), and serum markers of bone resorption and bone formation were also examined at baseline and 1, 3, 6, and 12 months after initiation of the medication regimen.

Results

At 12 months, mean mJOA score had improved in the teriparatide group and decreased in the alendronate group. Mean concentrations of bone formation and bone resorption biomarkers, mean spine BMD, and mean anterior-border height and spinal canal diameter of the fractured vertebrae were significantly greater in the teriparatide group than in the alendronate group. Mean VAS score, mean kyphotic angle of the fractured vertebrae, and incidence of new OVCFs were significantly smaller in the teriparatide group than in the alendronate group.

Conclusions

In patients with neurological deficits following new unstable OVCF and with surgical contraindications, teriparatide was better than alendronate at improving the BMD and the bone turnover parameters, as well as preventing aggravation of spinal cord compromise.

     

Computer prediction of allergen proteins from sequence-derived protein structural and physicochemical properties

BACKGROUND: Computational methods have been developed for predicting allergen proteins from sequence segments that show identity, homology, or motif match to a known allergen. These methods achieve good prediction accuracies, but are less effective for novel proteins with no similarity to any known allergen. METHODS: This work tests the feasibility of using a statistical learning method, support vector machines, as such a method. The prediction system is trained and tested by using 1005 allergen proteins from the Allergome database and 22,469 non-allergen proteins from 7871 Pfam families. RESULTS: Testing results by an independent set of 229 allergen and 6717 non-allergen proteins from 7871 Pfam families show that 93.0% and 99.9% of these are correctly predicted, which are comparable to the best results of other methods. Of the 18 novel allergen proteins non-homologous to any other proteins in the Swissprot database, 88.9% is correctly predicted. A further screening of 168,128 proteins in the Swissprot database finds that 2.9% of the proteins are predicted as allergen proteins, which is consistent with the estimated numbers from motif-based methods. CONCLUSIONS: Our study suggests that SVM is a potentially useful method for predicting allergen proteins and it has certain capability for predicting novel allergen proteins. Our software can be accessed at .     

双切口3至4块钢板固定治疗累及后内侧柱的复杂胫骨平台骨折15例疗效分析

目的 探讨双切口3至4块钢板固定治疗累及后内侧柱的Schatzker Ⅴ、Ⅵ型复杂胫骨平台骨折的临床疗效.方法 2013年1月至2015年12月采用前外侧联合后内侧倒L形双切口,外侧1块3.5 mm锁定钢板,内侧及后内侧2至3块3.5mm小钢板固定治疗累及后内侧柱的Schatzker Ⅴ、Ⅵ型复杂胫骨平台骨折患者15例,分析术后复位效果及随访时膝关节功能情况,评估手术临床疗效.结果 15例均获随访,随访时间18 ～30个月,平均24个月.术后骨折复位效果满意,末次随访时复位无丢失,骨折均愈合,膝关节活动度0 ～135°,平均115..膝关节功能采用HSS评分标准评定:优10例,良2例,可3例,差0例,优良率80％.结论 对于累及后内侧柱的SchatzkerⅤ、Ⅵ型复杂胫骨平台骨折,采用双切口,3至4块3.5 mm钢板固定,可以获得有效固定,膝关节功能恢复良好,并发症少,疗效满意.     

After Treatment with Methylene Blue is Effective against Delayed Encephalopathy after Acute Carbon Monoxide Poisoning

Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is the most severe and clinically intractable complication that occurs following acute CO poisoning. Unfortunately, the mechanism of DEACMP is still vague. Growing evidence indicates that delayed cerebral damage after CO poisoning is related to oxidative stress, abnormal neuro‐inflammation, apoptosis and immune‐mediated injury. Our recent report indicated that methylene blue (MB) may be a promising therapeutic agent in the prevention of neuronal cell death and cognitive deficits after transient global cerebral ischaemia (GCI). In this study, we aimed to investigate the potential of MB therapy to ameliorate the signs and symptoms of DEACMP. Rats were exposed to 1000 ppm CO for 40 min. in the first step; CO was then increased to 3000 ppm, which was maintained for another 20 min. The rats were implanted with 7‐day release Alzet osmotic mini‐pumps subcutaneously under the back skin, which provided MB at a dose of 0.5 mg/kg/day 1 hr after CO exposure. The results showed that MB significantly suppressed oxidative damage and expression of pro‐inflammatory factors, including tumour necrosis factor‐α and interleukin (IL)‐1β. MB treatment also suitably modulated mitochondrial fission and fusion, which is helpful in the preservation of mitochondrial function. Furthermore, MB dramatically attenuated apoptosis and neuronal death. Lastly, behavioural studies revealed that MB treatment preserved spatial learning and memory in the Barnes maze test. Our findings indicated that MB may have protective effects against DEACMP.