Search

The human–land relationship changes with the development of human society. In the contemporary context in which human activities dominate this relationship, revealing the spatial correlation between human activities and the natural environment provides a bridge to understanding and coordinating the human–land relationship. Currently, it is important to maintain the balance between humans and the environment. To measure the role of human activities in this relationship, this study took China as an example to explore spatial patterns through an indicator system and wavelet analysis at the city level in 2015, and a spatial deviation model to depict the relationship. The study revealed the following results: (1) The spatial pattern of human activity effects was bounded by the Hu Huanyong Line: The west side is a low-intensity area, and the east side was a medium- to high-intensity concentrated distribution area. The human activity scale was decreasing in the east, central area and west; the human activity structure declines from the metropolitan area to the core edge; and the high-value area of human activity is distributed as scattered points with the metropolitan area as the core. (2) Wavelet analysis results revealed that the spatial heterogeneity of each area on the east side of the Hu Huanyong Line showed the pattern of east > central > southwest > northeast, which indicates that the effects of human activities in the northeast are weakening, while those in the southwest are strengthening. Human activity effects on the east side of the Hu Huanyong Line had multiscale features, with the main characteristic scales being 60,000 km2, 150,000 km2, 300,000 km2 and 600,000 km2, which roughly corresponded to multiple cities, provinces, urban agglomerations and regions, respectively. (3) The overall pattern of the relationship between human activities and the natural environment was more consistent. The spatial deviation showed that the 500 m altitude contour

Neonicotinoids are the most widely used insecticides in modern agriculture, and their residues have been found in the environment and food. Previous studies reported that neonicotinoids exert toxic effects in various tissues, but whether they interfered with the female reproductive process remains unknown. In our present research, thiamethoxam was selected as a representative neonicotinoid to establish a mouse toxicity model with gavage. We found that thiamethoxam decreased the ovarian coefficient and disrupted the expression of female hormone receptors, subsequently affecting follicle development. Ovarian granulosa cells from the thiamethoxam exposure group underwent a high level of apoptosis. Using transcriptome analysis, we showed that thiamethoxam exposure altered the expression of multiple oocyte genes related to inflammation, apoptosis, and endoplasmic reticulum stress. Thiamethoxam also adversely affected oocyte and embryo development. Western blotting and fluorescence staining results confirmed that thiamethoxam affected the integrity of DNA, triggered apoptosis, promoted oxidative stress and endoplasmic reticulum stress, and impaired mitochondrial function. Collectively, our results indicated that thiamethoxam exposure disrupts ovarian homeostasis and decreases oocyte quality via endoplasmic reticulum stress and apoptosis induction.

In recent ten years, 3D printing technology has been developed rapidly. As an advanced technology, 3D printing has been used to fabricate complex and high-precision objects in many fields. 3D printing has several technologies. Among these technologies, photo-curing 3D printing was the earliest and most mature technology. In 1988, the first 3D printing machine which was based on photo-curing and called Stereo lithography Appearance (SLA) technology was produced by 3D system Corp. After 30 years of development, many new technologies based on photocuring mechanism emerged. Based on the different principle of pattern formation and character of printing technology, numerous photocuring 3D printing techniques, such as SLA, DLP, LCD, CLIP, MJP, two-photon 3D printing, holographic 3D printing and so on, have been developed. Photo-curing 3D printing has many advantages, such as high precision, smooth surface of printing objects, rapid printing speed and so on. Here, we would introduce five industrial photocuring 3D printing technologies, which are SLA, DLP, LCD, CLIP and MJP. The characters of the materials and the progress of the application of the technique in the biomedical field is also overviewed. At last, the difficulties and challenges of photo-curing 3D printing are also discussed., Highlights • Different techniques of photocuring 3D printing were overviewed. • The advantage, disadvantage and application of the different techniques of photocuring 3D printing were discussed. • The progress of photocuring 3D printing technique in biomedical application is commented. • The existing problems and challenges of photocuring 3D printing were presented.

The demand structure of resources for new economy is different from the traditional one in that its development may significantly change China’s economic location map and spatial pattern. Based on 343 administrative units of prefecture-level cities in China, this research constructs the measurement index system of terrestrial surface natural resources under the orientation of the new economic demands, this research mainly analyses the spatial distribution characteristics and geographical mechanism of natural resources by means of the spatial autocorrelation and spatial similarity calculation methods. The results show that: (1) The structure and endowment of natural resources under the orientation of the new economic demands need to be reexamined. The significance of a good environment and ecological resources has been highlighted. The coupling of resource elements better reveals the availability of natural resources. (2) The natural resources decrease from southeast to northwest, showing a pattern of “abundant in the south and east and scarce in the north and west”. Natural resources have a significant positive correlation in spatial distribution with two types of agglomeration: high-high agglomeration and low-low agglomeration, showing the local agglomeration feature of “high in the south and low in the north”. (3) Natural factors such as temperature, precipitation and altitude affect the spatial distribution of natural resources, with the temperature being the most significant. This indicates that the original natural environment and its role are the geographical mechanism for the formation and distribution of natural resources. The results could provide a reference for the development and the optimization of China’s new economy.

Nickel is a heavy metal element extensively distributed in the environment and widely used in modern life. Divalent nickel is one of the most widespread forms of nickel and has been reported as toxic to various tissues. However, whether exposure to divalent nickel negatively affects ovarian homeostasis and oocyte quality remains unclear. In this study, we found that 3 weeks of nickel sulfate exposure affected body growth and decreased the weight and coefficient of the ovary, and increased atretic follicles exhibiting enhanced apoptosis in granulosa cells. Further studies have found that nickel sulfate triggered ovarian fibrosis and inflammation via transforming growth factor-β1 and nuclear factor-κB pathways, and reduced oocyte development ability. In addition, nickel sulfate increased the level of reactive oxygen species, which induced DNA damage and early apoptosis. Moreover, it was found that nickel sulfate caused damage to the mitochondria showing aberrant morphology, distribution and membrane potential while decreased levels of histone methylation. To summarize, our results indicated that nickel sulfate exposure triggered ovarian fibrosis and inflammation and caused structural and functional disorders of mitochondria in oocytes, which consequently disturbed ovarian homeostasis and follicle development and decreased oocyte quality.

Acrylonitrile is an organic chemical synthetic monomer that is widely used in food packaging and manufacturing. Animal studies have reported that acrylonitrile is carcinogenic and toxic, but the effects on the female reproductive function in mammals are unknown. In the present study, we report that acrylonitrile treatment affects ovarian homeostasis in mice, resulting in impaired follicular development. Follicles in acrylonitrile-exposed mice exhibited high levels of inflammation and apoptosis, and acrylonitrile treatment interfered with oocyte development. Transcriptomics analysis showed that acrylonitrile altered the expression of oocyte genes related to apoptosis, oxidative stress, endoplasmic reticulum stress, and autophagy. Further molecular tests revealed that acrylonitrile induced early apoptosis, DNA damage, elevated levels of reactive oxygen species, endoplasmic reticulum abnormalities, and lysosomal aggregation. We also observed disruption of mitochondrial structure and distribution and depolarization of membrane potential. Finally, acrylonitrile treatment in female mice decreased the number and weight of offspring. Altogether, these findings suggest that acrylonitrile impairs the stability of the ovarian internal environment, which in turn affects oocyte development and reduces the number of offspring.

Activation of death receptor 5 (DR5) to induce apoptosis in cancer cells is an attractive strategy for cancer therapy. However, many tumor cell lines and primary tumors are resistant to DR5 targeted agents including recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and anti-DR5 agonistic antibodies. Here we identify tubulin proteins - primarily consisting of α and β subunits folded into microtubule polymers - as a crucial modulator of DR5 mediated apoptosis. Using affinity purification coupled with mass spectrometry, we found that DR5 interacts with both α- and β-tubulin proteins in cancer cells. Pharmacological disruption of microtubules increased DR5 protein expression and subsequently sensitized the cells to TRAIL-induced apoptosis. Similar results were observed by selectively silencing tubulin transcript using small RNA interference. We also demonstrate that tubulin/microtubule blockade augments TRAIL induced apoptosis by stabilizing DR5 protein. Together, our results link the tubulin/microtubule network to the stringent regulation of DR5 mediated apoptosis, which could lead to potential therapeutic strategies to enhance cancer therapy efficacy.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by interacting with membrane-bound angiotensin-converting enzyme 2 (ACE2), a vital element in the renin-angiotensin system (RAS), which regulates blood pressure, fluid balance, and cardiovascular functions. We herein evaluate existing evidence for the molecular alterations within the RAS pathway (e.g., ACE2 and angiotensin II) during SARS-CoV-2 infection and subsequent Coronavirus Disease 2019 (COVID-19). This includes reports regarding potential effect of RAS blockade (e.g., ACE inhibitors and angiotensin II receptor blockers) on ACE2 expression and clinical outcomes in patients with co-morbidities commonly treated with these agents. The collective evidence suggests a dual role for ACE2 in COVID-19, depending on the stage of infection and the coexisting diseases in individual patients. This information is further discussed with respect to potential therapeutic strategies targeting RAS for COVID-19 treatment.

Captan is a non-systematic fungicide widely used in agricultural production, and its residues have been found in the environment and daily diet. Previous studies confirmed that captan exerts several toxic effects on tissues, but its effect on the mammalian female reproductive system is unclear. In current study, we reported that captan affected mouse ovarian homeostasis and disrupted female hormone receptor expression, leading to impaired follicular development. Ovarian follicles from the captan exposure group showed an increased level of inflammation, endoplasmic reticulum stress and apoptosis. In addition, captan exposure disrupted oocyte development. Transcriptomic analysis indicated that captan changed multiple genes expression in oocytes, including autophagy and apoptosis. Further molecular testing showed that captan induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species, disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, captan triggered DNA damage, autophagy and early apoptosis, as shown by the enhanced levels of γ-H2AX, LC3, and Annexin-V and increased expression of related genes. Taken together, these results indicated that captan exposure impairs ovarian homeostasis and subsequently affects oocyte development.

Epilepsy is a neurological disorder characterized by sudden and unpredictable epileptic seizures, which incurs significant negative impacts on patients’ physical, psychological and social health. A practical approach to assist with the clinical assessment and treatment planning for patients is to process magnetoencephalography (MEG) data to identify epileptogenic zones. As a widely accepted biomarker of epileptic foci, epileptic MEG spikes need to be precisely detected. Given that the visual inspection of spikes is time consuming, an automatic and efficient system with adequate accuracy for spike detection is valuable in clinical practice. However, current approaches for MEG spike autodetection are dependent on hand-engineered features. Here, we propose a novel multiview Epileptic MEG Spikes detection algorithm based on a deep learning Network (EMS-Net) to accurately and efficiently recognize the spike events from MEG raw data. The results of the leave-k-subject-out validation tests for multiple datasets (i.e., balanced and realistic datasets) showed that EMS-Net achieved state-of-the-art classification performance (i.e., accuracy: 91.82% – 99.89%; precision: 91.90% – 99.45%; sensitivity: 91.61% – 99.53%; specificity: 91.60% – 99.96%; f1 score: 91.70% – 99.48%; and area under the curve: 0.9688 – 0.9998).

We propose a family of search directions based on primal-dual entropy in the context of interior-point methods for linear optimization. We show that by using entropy-based search directions in the predictor step of a predictor-corrector algorithm together with a homogeneous self-dual embedding, we can achieve the current best iteration complexity bound for linear optimization. Then, we focus on some wide neighborhood algorithms and show that in our family of entropy-based search directions, we can find the best search direction and step size combination by performing a plane search at each iteration. For this purpose, we propose a heuristic plane search algorithm as well as an exact one. Finally, we perform computational experiments to study the performance of entropy-based search directions in wide neighborhoods of the central path, with and without utilizing the plane search algorithms.

The paper believes that more attention should be paid to connect the high-speed railway and the development of the station area based on the completion of constructing the high-speed railway's backbones and frameworks. Therefore, We need capture the value and distribute the development value of regional development in high-speed railway station by taxes and comprehensive development guided by cross-domain bonus and through the mechanism of "LVC + TOD" in order to realize the coordinated development of high-speed railway and the city.

Therapeutic monoclonal antibodies (mAbs) are commonly administered to patients through intravenous (IV) infusion, which involves diluting the medication into an infusion solution (e.g., saline and 5% dextrose). Using the wrong diluent can cause product aggregation, which may compromise patient safety. We and others have shown that Herceptin® (trastuzumab) and Avastin® (bevacizumab) undergo rapid aggregation upon mixing with dextrose and human plasma in vitro. In this study, we evaluated the compatibility of a panel of 11 therapeutic mAbs with dextrose or saline and human serum. These mAbs were randomly selected for their distinct formulations and IgG isotypes (IgG1, IgG2, IgG4, and Fc-fusion protein). All the mAbs appeared to be compatible with saline and human serum. However, mAbs that were formulated at acidic pH (≤ 6.5) exclusively formed insoluble aggregates upon mixing with dextrose and serum. Such aggregation was not detected for the mAbs that are at neutral pH (7.2–7.5) or in buffers containing sodium chloride. Mass spectrometric analysis revealed that the insoluble aggregates were composed of mAb molecules and several serum proteins (e.g., complement proteins, apolipoprotein, fibronectin) that are characterized by an isoelectric point of pH 5.4–6.7. At proximate pH to the isoelectric point values, those abundant serum proteins appeared to undergo isoelectric precipitation with mAb molecules. Our observations highlight a potential risk of protein aggregation at the blood-IV interface if a diluent is incompatible with a specific mAb formulation. This information has implications in guiding the design of product formulations and the selection of the right diluent for intravenous infusion of therapeutic mAbs. Abbreviations: ADC: antibody-drug conjugate; D5W: 5% dextrose in water; IM: intramuscular; IV: intravenous; LC-MS/MS: liquid chromatography-tandem mass spectrometry; mAb: monoclonal antibody; SC: subcutaneous; pI: isoelectric point

This chapter aims to study other support surfaces. It discusses wheelchair design and modification, including some special cases. The chapter presents patient support surfaces for both the hospital bed and the operating table. Paralyzed patients spend their lifetime in a wheelchair or bed. One of the major complications facing them is pressure sores. For patients confined to bed, regular turning is an effective way of reducing the risk. Even for patients in the surgical environment on an operating table, regular relief is the most useful method of pressure sore prevention although this may not be common practice. Wheelchair patients frequently develop pressure sores on the buttocks because of sitting too long without lifting up to relieve the pressure. For preventing pressure sores, of course, many details of wheelchair design must be considered. A proper wheelchair for an individual should have proper armrest height, sling width and depth, backrest height, and footrest height.

Osteosarcoma over distal fibula is a rare disease. Wide resection of a malignant tumor of the distal fibula may lead to severe lateral ankle instability, lateral displacement of the talus, and even severe ankle osteoarthritis. We present a case of a 16-year-old girl presented with painful swelling over lateral ankle. Radiography revealed an expansile lesion and periosteal reaction over the distal fibula. Magnetic resonance imaging revealed a solitary heterogenous lesion. Histological examination of the open biopsy specimen revealed osteosarcoma. Wide resection and biological reconstruction with allograft followed by skin graft was performed. Over 12-year follow-up, radiography revealed good union. The lateral malleolus allograft appeared to support fair lateral stability over the ankle. The patient had good functional recovery after the long-term follow-up. Osteosarcoma over distal fibula can be treated with wide resection and allograft reconstruction with good functional recovery after long-term follow-up.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents an unprecedented challenge to global public health. At the time of this review, COVID-19 has been diagnosed in over 40 million cases and associated with 1.1 million deaths worldwide. Current management strategies for COVID-19 are largely supportive, and while there are more than 2000 interventional clinical trials registered with the U.S. National Library of Medicine (clinicaltrials.gov), results that can clarify benefits and risks of candidate therapies are only gradually becoming available. We herein describe recent advances in understanding SARS-CoV-2 pathobiology and potential therapeutic targets that are involved in viral entry into host cells, viral spread in the body, and the subsequent COVID-19 progression. We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-CoV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-CoV-2, such as REGN-COV2 (an antibody cocktail), as well as recombinant human soluble ACE2 protein to counteract SARS-CoV-2 binding to the transmembrane ACE2 receptor in target cells. Finally, we discuss potential drug resistance mechanisms and provide thoughts regarding clinical trial design to address the diversity in COVID-19 clinical manifestation. Of note, preventive vaccines, cell and gene therapies are not within the scope of the current review.

We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2 kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and α-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5 Angstrom from the α-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction.

Glycans or carbohydrates attached to therapeutic glycoproteins can directly affect product quality, safety and efficacy, and therefore must be adequately analyzed and controlled throughout product life cycles. However, the complexity of protein glycosylation poses a daunting analytical challenge. In this study, we evaluated the utility of a lectin microarray for assessing protein glycans. Using commercial lectin chips, which contain 45 lectins toward distinct glycan structures, we were able to determine the lectin binding patterns of a panel of 15 therapeutic proteins, including 8 monoclonal antibodies. Lectin binding signals were analyzed to generate glycan profiles that were generally consistent with the known glycan patterns for these glycoproteins. In particular, the lectin-based microarray was found to be highly sensitive to variations in the terminal carbohydrate structures such as galactose versus sialic acid epitopes. These data suggest that lectin microarray could be used for screening glycan patterns of therapeutic glycoproteins.

Therapeutic monoclonal antibodies (mAbs) are glycoproteins produced by living cell systems. The glycan moieties attached to the proteins can directly affect protein stability, bioactivity, and immunogenicity. Therefore, glycan variants of a glycoprotein product must be adequately analyzed and controlled to ensure product quality. However, the inherent complexity of protein glycosylation poses a daunting analytical challenge. This review provides an update of recent advances in glycan analysis, including the potential utility of lectin-based microarray for high throughput glycan profiling. Emphasis is placed on comparison of the major types of analytics for use in determining unique glycan features such as glycosylation site, glycan structure, and content.

Cofilin regulates reorganization of actin filaments (F-actin) in eukaryotes. A recent finding has demonstrated that oxidation of cofilin by taurine chloramine (TnCl), a physiological oxidant derived from neutrophils, causes cofilin to translocate to the mitochondria inducing apoptosis (F. Klamt et al. Nat. Cell Biol.11:1241-1246; 2009). Here we investigated the effect of TnCl on biological activities of cofilin in vitro. Our data show that TnCl-induced oxidation of recombinant human cofilin-1 inhibits its F-actin-binding and depolymerization activities. Native cofilin contains four free Cys and three Met residues. Incubation of oxidized cofilin with DTT does not lead to its reactivation. A double Cys to Ala mutation on the two C-terminal Cys shows similar biological activities as the wild type, but does not prevent the TnCl-induced inactivation. In contrast, incubation of oxidized cofilin with methionine sulfoxide reductases results in its reactivation. Phosphorylation is known to inhibit cofilin activities. We found that Met oxidation also prevents phosphorylation of cofilin, which is reversed by incubating oxidized cofilin with methionine sulfoxide reductases. Interestingly, intact protein mass spectrometry of the oxidized mutant indicated one major oxidation product with an additional mass of 16 Da, consistent with oxidation of one specific Met residue. This residue was identified as Met-115 by peptide mapping and tandem mass spectrometry. It is adjacent to Lys-114, a known residue on globular-actin-binding site, implying that oxidation of Met-115 disrupts the globular-actin-binding site of cofilin, which causes TnCl-induced inactivation. The findings identify Met-115 as a redox switch on cofilin that regulates its biological activity.

The passage aims at solving the problems resulted from the optimized process of Particle Swarm Optimization (PSO), which might reduce the population diversity, cause the algorithm to convergence too early, etc. A whole new mutable simulated annealing particle swarm optimization is proposed based on the combine of the simulated annealing mechanism and mutation. This new algorithm substitutes the Metropolis criterion in the simulated annealing mechanism for mutagenic factors in the process of mutation, which both ensures the diversity of the particle swarm, and ameliorates the quality of the swarm, so that this algorithm would convergence to the global optimum. According to the result of simulated analysis, this hybrid algorithm maintains the simplicity of the particle swarm optimization, improves its capability of global optimization, and finally accelerates the convergence and enhances the precision of this algorithm.

The rapid development of the optically pumped magnetometer (OPM) has offered a much more flexible method for magnetoencephalography (MEG). Without using liquid helium and its associated dewar device in the OPM detectors, the large and expensive magnetically shielded room (MSR) for traditional MEG systems could be replaced by a compact shield. In the present work, an economic and compact cylindrical shield was designed and built to meet the low-field working requirement of the OPM in detecting human brain neuronal activities. The performance of the compact shield was evaluated and further compared with that of a commercial MSR. Our results showed that the residual magnetic fields and background noise of the compact shield were lower than or comparable to those of the MSR. The remnant field in the shield is found to be 4.2 nT, a factor of 13 000 smaller than the geomagnetic field which is applied to the transverse direction of the shield, and the longitudinal shielding factors measured using a known alternating-current magnetic field are approximately 191, 205, and 3130 at 0.1 Hz, 1 Hz, and 10 Hz, respectively; in addition, the evoked dynamic waveforms in the human auditory cortex that were recorded separately in these two shields demonstrated consistency. Our findings suggested that a compact shield is feasible for OPM-based MEG applications with high performance and low cost.

Rationale The occurrence of peripheral neuropathy associated with non-Hodgkin's lymphoma (NHL) is uncommon. And autoimmunity may play an important role. We report a case of the patient with NHL, has sensorimotor demyelinating polyneuropathy. Patient concerns The patient presented with a 1-month history of progressive numbness at the distal extremities and motor weakness of the lower limbs. Meanwhile, patient also endorsed a painful lump on her right cheek. And then the enlarged cervical and supra clavicular lymph nodes were observed on admission. Biopsy of the lymph nodes showed NHL. Serum IgM antibodies against GM1 and GD1b were also positive. Diagnosis Biopsy of the lymph nodes showed NHL. Serum IgM antibodies against GM1 and GD1b were also positive. Thus, the patience was diagnosed with lymphoma and sensorimotor polyneuropathy. Interventions Patient refused the further treatment. Outcomes After 11-month follow-up, the weakness of bilateral lower limbs worsens. Lessons We have presented a case of NHL involving peripheral polyneuropathy with IgM antibodies against GM1 and GD1b. Patients may initially present with peripheral nerve complications or develop them during the course of lymphoma, even when in remission. This could complicate the diagnosis of peripheral polyneuropathy secondary to NHL.

Objective To investigate the role of dexmedetomidine in stress control in moderate and severe traumatic brain injury (TBI) and its influence on neuroendocrine system. Methods Ninety moderate or severe TBI patients (GCS 6-13) were admitted to ICU from May 2009 to January 2012, and they were divided into three groups according to the order of admission. Patients in group A (n=32) received 0.5-1.0μg/kg dexmedetomidine within 30min, maintained with 0.2-0.6μg/(kg.h) dexmedetomidine for 24h, and morphine was administered by intravenous injection when necessary; patients in group B (n=31) received a 0.5-2.0mg/kg loading dose of propofol within 10min, maintained with 1.0-3.0mg/(kg.h) for 72h, and morphine was administered by intravenous injection when necessary; patients in group C (n=27) received an intramuscular injection of pethidine or other optional drugs as control. A comprehensive evaluation was performed using Riker sedation-agitation scale combined with physiological and physical response indicators. The blood pressure, heart rate, respiration, tidal volume, arterial blood gas, plasma cortisol, plasma β-endorphin (β-EP), peripheral WBC count and blood glucose were measured and compared in 3 groups. Results The sedation rate of single-drug (i.e., without morphine administration) in groups A, B and C was 86.7%, 80.6% and 77.8% respectively, and no significant difference was found among 3 groups (P>0.05). The mean arterial blood pressure at 30 min after administration was lower than that before administration in group A (P0.05). The WBC count and plasma cortisol level at 24h after treatment were lower than those before administration of the drugs in group A (P0.05). Conclusions Dexmedetomidine could alleviate the stress as a result of moderate and severe TBI, and its anti-stress and sedative effects were similar to those of propofol, but it is necessary to monitor the blood pressure. β-EP may play a coordinating role in the early stage of effect of dexmedetomidine. DOI: 10.11855/j.issn.0577-7402.2013.11.011

Analog filtering and digital signal processing algorithms in the preprocessing modules of an electrocardiographic device play a pivotal role in providing high-quality electrocardiogram (ECG) signals for analysis, interpretation, and presentation (display, printout, and storage). In this article, issues relating to inaccuracy of ECG preprocessing filters are investigated in the context of facilitating efficient ECG interpretation and diagnosis. The discussion covers 4 specific ECG preprocessing applications: anti-aliasing and upper-frequency cutoff, baseline wander suppression and lower-frequency cutoff, line frequency rejection, and muscle artifact reduction. Issues discussed include linear phase, aliasing, distortion, ringing, and attenuation of desired ECG signals. Due to the overlapping power spectrum of signal and noise in acquired ECG data, frequency selective filters must seek a delicate balance between noise removal and deformation of the desired signal. Most importantly, the filtering output should not adversely impact subsequent diagnosis and interpretation. Based on these discussions, several suggestions are made to improve and update existing ECG data preprocessing standards and guidelines.

To explore chronic heterotypic stressors induced proliferation and activation of mast cells in gastric antrum mucosa by ultrastructure alterations of mast cells, chronic unpredictable heterotypic stressors were used as a study model. The mean immunofluorescence magnitude of mast cell protease 1 (MCP-1) taken from chronic stress rats were 37.4±7.7, significantly higher (p

Many therapeutic monoclonal antibodies (mAbs) are clinically administered through intravenous infusion after mixing with a diluent, e.g., saline, 5% dextrose. Such a clinical setting increases the likelihood of interactions among mAb molecules, diluent, and plasma components, which may adversely affect product safety and efficacy. Avastin® (bevacizumab) and Herceptin® (trastuzumab), but not Remicade® (infliximab), were shown to undergo rapid aggregation upon dilution into 5% dextrose when mixed with human plasma in vitro; however, the biochemical pathways leading to the aggregation were not clearly defined. Here, we show that dextrose-mediated aggregation of Avastin or Herceptin in plasma involves isoelectric precipitation of complement proteins. Using mass spectrometry, we found that dextrose-induced insoluble aggregates were composed of mAb itself and multiple abundant plasma proteins, namely complement proteins C3, C4, factor H, fibronectin, and apolipoprotein. These plasma proteins, which are characterized by an isoelectronic point of 5.5-6.7, lost solubility at the resulting pH in the mixture with formulated Avastin (pH 6.2) and Herceptin (pH 6.0). Notably, switching formulation buffers for Avastin (pH 6.2) and Remicade (pH 7.2) reversed their aggregation profiles. Avastin formed little, if any, insoluble aggregates in dextrose-plasma upon raising the buffer pH to 7.2 or above. Furthermore, dextrose induced pH-dependent precipitation of plasma proteins, with massive insoluble aggregates being detected at pH 6.5-6.8. These data show that isoelectric precipitation of complement proteins is a prerequisite of dextrose-induced aggregation of mAb in human plasma. This finding highlights the importance of assessing the compatibility of a therapeutic mAb with diluent and human plasma during product development.

Background Multistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality. Methods and Findings In the “pre-intervention 2010” (from January 2010 to December 2010) and “pre-intervention 2011” (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the “post-intervention 2012” (from July 2012 to June 2013) and “post-intervention 2013” (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6–18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27–141)/43 d (IQR 15–113) to 5 d (IQR 2–12)/5 d (IQR 2–13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239–0.620] and 0.380 [95% CI 0.233–0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226–0.603] and 0.361 [95% CI 0.221–0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52. Conclusions Our results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART., In a before and after analysis, Zunyou Wu and colleagues assess the impact on mortality of an HIV test and treat intervention in two counties in Guangxi, China., Editors' Summary Background Every year, about 2.1 million people (mostly living in resource-limited countries) are newly infected with HIV, the virus that causes AIDS and that has killed 39 million people over the past three decades. HIV, which is usually transmitted through unprotected sex with an infected individual, gradually destroys CD4 lymphocytes and other immune system cells, leaving HIV-positive individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-positive individuals died within ten years of infection. Then, in 1996, effective antiretroviral therapy (ART) became available, and, for people living in high-income countries, HIV became a chronic condition. But ART was expensive, so HIV/AIDS remained largely untreated and fatal in resource-limited countries. In 2003, the international community began to work towards achieving universal ART coverage. By 2013, about 12.9 million people living with HIV (a third of all HIV-positive people) had access to ART, and the rate of AIDS-related deaths had fallen by a third from its 2005 peak. Why Was This Study Done? Unfortunately, in many countries, late diagnosis of HIV infection, incomplete linkage to care after diagnosis, and high rates of loss to follow-up before and after ART initiation remain major barriers to effective HIV/AIDS treatment and to maximization of the preventative benefits of ART: as well as keeping HIV-positive people healthy, ART also reduces their chances of transmitting HIV to a sexual partner. Here, the researchers investigate whether a simplified “test and treat” intervention can reduce HIV/AIDS mortality (death) rates in China by reducing these barriers. Currently, CD4 testing is offered to people in China only after an initial HIV diagnosis has been confirmed using a second type of test. This standard-of-care policy introduces a delay into ART initiation because a CD4 count below 350 cells/μl blood is the primary determinant of eligibility for treatment through the Chinese national free ART program. By contrast, the simplified test and treat intervention, which is designed to be completed within a week of the patient’s first positive HIV test result, incorporates immediate HIV confirmatory testing, pre-ART CD4 testing, pre-treatment counseling, and ART initiation regardless of CD4 count. What Did the Researchers Do and Find? The researchers followed about 1,000 patients who tested positive for HIV at health care facilities in two counties in Guangxi (one of the Chinese provinces most heavily affected by HIV/AIDS) in two 12-month pre-intervention phases, during which patients followed the standard-of-care process, and two 12-month post-intervention phases, during which patients were offered the simplified test and treat intervention. About 65% and 97% of the patients received baseline CD4 testing during the pre-intervention and post-intervention phases, respectively. Following the structural intervention, the time from HIV confirmation to ART initiation decreased from around 50 days to five days, and the proportion of individuals who initiated ART increased from below 36% to above 90% among all the patients and from below 47% to above 93% among patients eligible for treatment under the standard-of-care policy. Notably, the mortality rate decreased from about 26% to about 10% among all the study participants following the intervention, and from about 37% to about 13% among the participants eligible for ART under the standard-of-care policy. Finally, the researchers estimated that the cost of each death prevented by the intervention was about US$234.52 over the study period; importantly, most of this cost was accrued during the initial year of the intervention. What Do These Findings Mean? These findings indicate that, in the two Chinese counties involved in this study, the simplified test and treat intervention—which incorporated a streamlined, standardized time frame for HIV diagnosis and expanded access to ART—promoted successful engagement in care among HIV-positive individuals and was associated with a 62% reduction in mortality. Moreover, the intervention required very little further investment once it had been set up and should, therefore, be sustainable. Because the design of the simplified test and treat intervention took into account the characteristics of the HIV epidemic and the health care structure in China, these findings may not be fully generalizable to other countries. In addition, reliance on a pre-intervention/post-intervention study design, rather than a controlled trial, may limit the accuracy of these findings. Nevertheless, these results suggest that the implementation of integrated HIV testing and immediate access to ART regardless of CD4 count has the potential to optimize the individual and public health impacts of ART by ensuring that fewer patients are lost along the multistage continuum of HIV testing and treatment. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001874. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on universal access to ART and on HIV/AIDS in China; Avert also provides personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its Consolidated Guidelines on the Use of Antiretroviral Therapy for Treating and Preventing HIV Infection, its recently released consolidated guidelines on HIV testing, and information on the WHO/UNAIDS Treatment 2.0 strategy, an initiative to expand access to HIV testing and ART The UNAIDS Fast-Track Strategy to End the AIDS Epidemic by 2030 provides up-to-date information about the AIDS epidemic and efforts to halt it, including progress towards universal access to antiretroviral therapy

Genetics, one of the core courses of biological field, play a key role in biology teaching and research. In fact, there exists high similarity between many genetic knowledge and physical knowledge. Due to strong abstract of genetic contents and the weak basis of genetics, some students lack of interests to study genetics. How to apply the strong physical knowledge which students had been learned in the middle school in genetics teaching is worthwhile for genetics teachers. In this paper, we would like to introduce an infiltrative teaching model on applying physical knowledge into genetic contents by establishing the intrinsic logistic relationship between physical knowledge and genetic knowledge. This teaching model could help students more deeply understand genetic knowledge and enhance students' self-studying ability as well as creating ability.

The authors have designed a multirate digital signal processing algorithm to detect heartbeats in the electrocardiogram (ECG). The algorithm incorporates a filter bank (FB) which decomposes the ECG into subbands with uniform frequency bandwidths. The FB-based algorithm enables independent time and frequency analysis to be performed on a signal. Features computed from a set of the subbands and a heuristic detection strategy are used to fuse decisions from multiple one-channel beat detection algorithms. The overall beat detection algorithm has a sensitivity of 99.59% and a positive predictivity of 99.56% against the MIT/BIH database. Furthermore this is a real-time algorithm since its beat detection latency is minimal. The FB-based beat detection algorithm also inherently lends itself to a computationally efficient structure since the detection logic operates at the subband rate. The FB-based structure is potentially useful for performing multiple ECG processing tasks using one set of preprocessing filters.