牙线牵引辅助内镜黏膜下剥离术治疗胃角黏膜病变的疗效（含视频）

目的 探讨牙线牵引辅助内镜黏膜下剥离术（endoscopic submucosal dissection, ESD）治疗胃角黏膜病变的疗效。方法 回顾性分析2015年1月—2018年12月厦门大学附属第一医院内镜中心收治的127例胃角黏膜病变患者病例资料。根据术中手术方法,将患者分为牙线牵引辅助ESD组（牵引组,n=51）和传统ESD组（传统组,n=76）,同时把41例胃角纤维化病例也分为牵引组(n=23)和传统组(n=18)。对比分析手术时间、整块切除率、治愈性切除率及出血、肌层损伤、穿孔等不良事件发生率等指标。结果 牵引组与传统组病例年龄、性别、病变大小及病变形态差异无统计学意义（P＞0.05）。牵引组手术时间较传统组明显缩短[（65.4±36.5） min比(103.5±43.2) min,P=0.012],病变整块切除率[100.00%(51/51)比90.79%(69/76),P=0.026]及治愈性切除率均更高[94.12%(48/51)比81.58%(62/76),P=0.042],且剥离过程中肌层损伤[5.88%(3/51)比25.00%（19/76）,P=0.010]及术中出血更少[47.06%（24/51）比82.89%（63/76）,P=0.010]。传统组2例(2.63%)纤维化病例穿孔,牵引组无穿孔病例,穿孔发生率差异无统计学意义（P=0.243）。在胃角纤维化病例中,牵引组手术时间较传统组明显缩短[（81.4±29.3） min比(119.3±37.6） min,P=0.010],病变整块切除率[100.00%（23/23）比72.22%(13/18）,P=0.007]及治愈性切除率均更高[95.65%(22/23)比72.22%(13/18),P=0.035],且剥离过程中肌层损伤[8.70%(2/23)比72.22%(13/18）,P=0.001]及术中出血更少[78.26%(18/23)比100.00%(18/18),P=0.035]。结论 牙线牵引辅助ESD治疗胃角黏膜病变及有纤维化的胃角病变安全有效,与传统ESD相比,手术时间更短,治愈率更高,不良事件发生率更低。     

颅内压监测在重型创伤性颅脑损伤患者中的应用进展

重型创伤性颅脑损伤(TBI)后患者颅内压(ICP)升高是导致死亡或致残的主要原因之一。ICP监测是持续监测患者颅内情况和指导处理异常ICP的重要手段。本文就近年来有关ICP监测在重型TBI患者中的临床应用进行综述。     

Characterization of ibrutinib‐sensitive and ‐resistant mantle lymphoma cells

Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B‐cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one‐third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib‐sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti‐tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach.     

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.     

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 .