Search

Yan Cui, Xuena Li, Bulin Du, Yao Diao, Yaming Li Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Yaming LiDepartment of Nuclear Medicine, The First Hospital of China Medical University, North Nanjing Street 155, Shenyang, Liaoning 110001, People’s Republic of ChinaTel +86-24-83282142Fax +86-24-83282671Email ymli2001@163.comPurpose: This study aimed to evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in expression of tumor programmed death ligand-1 (PD-L1) expression and prognostic significance of 18F-FDG PET/CT at different PD-L1 status in patients with lung adenocarcinoma.Patients and Methods: Seventy-three patients with primary lung adenocarcinoma who received 18F-FDG PET/CT before treatment were retrospectively included in this study. Expression of tumor PD-L1, programmed death-1 (PD-1) and glucose metabolic parameters were evaluated.Results: Tumor PD-L1 expression was positively correlated with maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), hexokinase II (HK-II) and glucose transporter 1 (GLUT-1) (P< 0.0001 for all). SUVmax was a unique independent predictor of tumor PD-L1 expression, with an optimal cut-off value of 9.5. For all the patients, tumor stage (P< 0.001) and SUVmax (P=0.009) were independent prognostic indicators of disease-free survival (DFS)/progression-free survival (PFS) while carcino-embryonic antigen (CEA) (P=0.003), Ki67 (P=0.042), PD-L1 (P=0.048) and TLG (P=0.004) were independent prognostic indicators of overall survival (OS). Tumor stage (P=0.004) and SUVmax (P=0.022) were independent prognostic indicators of DFS/PFS while TLG (P=0.012) and CEA (P=0.045) were independent prognostic indicators of OS in the PD-L1-positive group. In the PD-L1-negative group, tumor stage (P=0.002) and CEA (P=0.006) were unique independent prognostic indicators of DFS/PFS and OS, respectively.Conclusion: 18F-FDG PET/CT may potentially predict tumor PD-L1 expression and play a role in predicting prognosis of PD-L1/PD-1 immunotherapy in lung adenocarcinoma.Keywords: 18F-fluorodeoxyglucose, positron emission tomography, programmed death ligand-1, lung adenocarcinoma, prognosis

Yifan Diao,1 Mingshuang Li,1 Zhiran Huang,1 Jing Sun,1 Yoke Ling Chee,2 Yunali Liu1 1School of Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, People’s Republic of China; 2Third World Network, George Town 10400, Penang, MalaysiaCorrespondence: Jing Sun; Yunali LiuSchool of Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdansantiao, Dongcheng District, Beijing 100730, People’s Republic of ChinaTel/Fax +86-10-65105537Email sunjing@sph.pumc.edu.cn; yliu@pumc.edu.cnAbstract: China’s healthcare reform aims to provide affordable and equitable basic healthcare for all by 2020. Access to medicines is an essential part of the healthcare. The efforts of promoting access to medicines have been moving from meeting the needs of the basic healthcare, towards increasingly dedicated resources to offer breakthrough therapies. Looking at access to novel medicines from a health system perspective, and placing the changes China has made into that system context, this paper makes a comprehensive review of the progress of access to novel medicines in China. The review drew on two sources of information, which included desk review of published and grey literature, and key informant interview. Five hurdles were identified which create barriers of access to novel medicines, ranging from regulation and financing of medicines, intellectually property rights protection, and development of innovation capacity, to other health system components. Multiple policies have been implementing in China to remove the multiple access barriers gradually. Universal access to medicines has been moving from towards the basic common conditions to the world breakthrough technologies. We see cause for optimism, but recognize that there is a long way to go. Achieving broader and better access to modern medicines for Chinese patients will require multiple and coordinated government efforts, which would need to target the whole lifecycle regulation of novel medicines with a health system perspective, from balancing IP protection, strengthening R&D and public health, to appropriate regulatory approach and financing mechanism, and to supply chain management, as well as smart use.Keywords: access to novel medicines, regulatory, affordability, IP, R&D, health system

Flavonoids from mulberry leave (FML) are natural flavonoids, and Candida tropicalis (CT) is yeast like microbe. In this study, forty-eight male calves were selected with born weight (40.5±0.7 kg) and 20±2 days age, divided into 4 groups randomly. FML was supplemented in a dairy calf starter at 2 g/d per calf before weaning, or 4 g/d per calf after weaning (FML group), while CT was added in a dairy calf starter at 1 g/d per calf (CT group). Our results showed that FML could be used to enhance body weight (BW) of calves through enhancing apparent digestibility of ether extract (EE) of the diet, and increased the levels of serum growth hormone (GH) and insulin-like growth factors 1 (IGF-1) in calves after the age of 56 days. CT enhanced the BW of calves before weaning through increasing the apparent digestibility of neutral detergent fiber (NDF) of the diet, and elevated the apparent digestibility of EE of the diet of calves after weaning through increasing the level of serum IGF-1 in calves. Furthermore, the mixture of FML and CT plays a synergistic role in enhancing growth, improving feed intake and nutriment digestibility. In conclusion, FML and CT could be used as additives to increase growth and nutrient digestibility in calves.

Hongtao Sun,1,* Maohua Zheng,2,* Yanmin Wang,1 Yunfeng Diao,1 Wanyong Zhao,1 Zhengjun Wei1 1Sixth Department of Neurosurgery, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, 2Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2) in the course of mild hypothermia treatment (MHT) for treating severe traumatic brain injury (sTBI). Methods: There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), and cerebral perfusion pressure (CPP) were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Results: Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Conclusion: Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome. Keywords: severe traumatic brain injury, hypothermia, brain tissue partial pressure of oxygen, therapy

Hong-tao Sun,1,* Maohua Zheng,2,* Yanmin Wang,1 Yunfeng Diao,1 Wanyong Zhao,1 Zhengjun Wei1 1Sixth Department of Neurosurgery, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, 2Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of the study was to evaluate the clinical value of multiple brain parameters on monitoring intracranial pressure (ICP) procedures in the therapy of severe traumatic brain injury (sTBI) utilizing mild hypothermia treatment (MHT) alone or a combination strategy with other therapeutic techniques. A total of 62 patients with sTBI (Glasgow Coma Scale score

Trypanosomatida parasites, such as Trypanosoma and Leishmania, are the cause of deadly diseases in many third world countries. The three dimensional structure of their mitochondrial DNA, known as kinetoplast DNA (kDNA), is unique since it is organized into several thousands of minicircles that are topologically linked. How and why the minicircles form such a network have remained unanswered questions. In our previous work we have presented a model of network formation that hypothesizes that the network is solely driven by the confinement of minicircles. Our model shows that upon confinement a percolation network forms. This network grows into a space filling network, called saturation network, upon further confinement of minicircles. Our model also shows, in agreement with experimental data, that the mean valence of the network (that is, the average number of minicircles topologically linked to any minicircle in the network) grows linearly with minicircle density. In our previous studies however we disregarded DNA flexibility and used rigid minicircles to model DNA, here we address this limitation by allowing minicircles to be flexible. Our numerical results show that the topological characteristics that describe the growth and topology of the minicircle networks have similar values to those observed in the case of rigid minicircles suggesting that these properties are robust and therefore a potentially adequate description of the networks observed in Trypanosomatid parasites.

It is well known that genomic materials (long DNA chains) of living organisms are often packed compactly under extreme confining conditions using macromolecular self-assembly processes but the general DNA packing mechanism remains an unsolved problem. It has been proposed that the topology of the packed DNA may be used to study the DNA packing mechanism. For example, in the case of (mutant) bacteriophage P4, DNA molecules packed inside the bacteriophage head are considered to be circular since the two sticky ends of the DNA are close to each other. The DNAs extracted from the capsid without separating the two ends can thus preserve the topology of the (circular) DNAs. It turns out that the circular DNAs extracted from bacteriophage P4 are non-trivially knotted with very high probability and with a bias toward chiral knots. In order to study this problem using a systematic approach based on mathematical modeling, one needs to introduce a DNA packing model under extreme volume confinement condition and test whether such a model can produce the kind of knot spectrum observed in the experiments. In this paper we introduce and study a model of equilateral random polygons con_ned in a sphere. This model is not meant to generate polygons that model DNA packed in a virus head directly. Instead, the average topological characteristics of this model may serve as benchmark data for totally randomly packed circular DNAs. The difference between the biologically observed topological characteristics and our benchmark data might reveal the bias of DNA packed in the viral capsids and possibly lead to a better understanding of the DNA packing mechanism, at least for the bacteriophage DNA. The purpose of this paper is to provide information about the knot spectrum of equilateral random polygons under such a spherical confinement with length and confinement ratios in a range comparable to circular DNAs packed inside bacteriophage heads.

Chronic obstructive pulmonary disease(COPD)is a group of lung diseases characterized by persistent airflow limitation, often accompanied by chronic hypoxia. This chronic hypoxia can lead to structural and functional changes in the walls of blood vessels throughout the body, causing vascular injury and altered vascular reactivity. The retina and choroid are key ocular structures with rich blood supply and are particularly prone to microstructural changes due to ischemia and hypoxia. Optical coherence tomography(OCT), an ideal tool for observing these microstructural changes, serves as a non-invasive method for assessing retinal microstructures and microvascular pathology. Currently, there is a lack of comprehensive reviews summarizing OCT-based morphological changes in the eyes of COPD patients. This paper provides an in-depth review of existing studies on ocular OCT in COPD patients, focusing on structural and blood flow changes in the retina and choroid. The primary goal of this review is to summarize the impact of COPD on ocular microstructures, explore the underlying mechanisms of these morphological changes, and offer new perspectives for assessing eye diseases in COPD patients.

Abstract Background This study retrospectively compared short-term clinical outcomes and complications of minimally invasive surgery transforaminal lumbar interbody fusion(MIS-TLIF)and endoscopic lumbar interbody fusion(Endo-LIF))for two-segmental lumbar degenerative disease, aiming to guide spine surgeons in selecting surgical approaches. Methods From January 2019 to December 2023, 30 patients were enrolled,15 in the MIS-TLIF group and 15 in the Endo-LIF group. All patients were followed up for more than 3 months after surgery and the following information was recorded: (1)surgery time, difference in hemoglobin between preoperative and postoperative, surgical costs, first time out of bed after operation, postoperative hospitalization time, postoperative complication; (2) ODI score (The Oswestry Disability Index), leg and back VAS score (Visual Analogue Scale), and lumbar vertebra JOA score (Japanese Orthopaedic Association Scores); (3) MacNab score at final follow-up to assess clinical outcome, CT to evaluate lumbar fusion. Results There were significant differences between the two groups regarding operation time and cost, with the MIS-TLIF group performing significantly better. Intraoperative bleeding was considerably less in the Endo-LIF group compared to the MIS-TLIF group. However, there were no significant differences in the time of the first postoperative ambulation, postoperative hospitalization time, and postoperative complications. There was no significant difference in preoperative VAS, ODI, and JOA between the two surgical groups There were no significant differences in VAS(leg), ODI, and JOA scores between the two groups before and at 1 day,7 days, 1 month, 3 months and final follow-up. However, at 1 day postoperatively, the VAS( back)score in the Endo-LIF group was lower than that in the MIS-TLIF group, and the difference was statistically significant. At the final follow-up, all patients achieved grade III and above according to the Bridwell criteria, and there was no significant difference between the two surgical groups compared to each other. According to the MacNab score at the final follow-up, the excellent rate was 80.00% in the Endo-LIF group and 73.33% in the MIS-TLIF group, with no significant difference between the two groups. Conclusion There was no significant difference in short-term efficacy and safety between Endo-LIF and MIS-TLIF for two-segment degenerative lumbar diseases. MIS-TLIF has a shorter operative time and lower costs, while Endo-LIF causes less tissue damage, blood loss, and early postoperative pain, aiding long-term recovery. Both MIS-TLIF and Endo-LIF are promising for treating two-segment lumbar degenerative disease. The choice of a surgical procedure depends on the patient’s financial situation, their ability to tolerate surgery, and the surgeon’s expertise.

ObjectivesThe demand for energy in outdoor work and survival is increasing, and there are some significant shortcomings in the existing conventional energy supply methods, such as the need to carry a large amount of fuel for conventional generators and heavy weight of cells. Solar photovoltaic/thermal (PV/T) technology can effectively solve the problem of lack of energy for outdoor survival and field work. However, most of the existing PV/T collectors are rigid structures with large weight and are not easy to carry.MethodsA light and thin PV/T module based on the combination of a Cu(In,Ga)Se2(CIGS) thin film battery and a piece of capillary network were proposed. The energy collection performance of the module and the impact of water flow rate on the photoelectric and photothermal conversion efficiency of the module were studied experimentally.ResultsUnder the typical Shanghai climate conditions, the all-day electrical efficiency and thermal efficiency of the module are 13.04% and 22.50%, respectively. Under experimental conditions with an average irradiance of 760 ‍W/m², the optimal energy collection performance of this PV/T is achieved when the water flow rate is 2.1 ‍L/min. The cooling water in the capillary network can effectively reduce the cell temperature (by 10 ℃) and improve the energy utilization efficiency (by 23.94%).ConclusionsThe module has the characteristics of high power density, light weight and flexibility, and can be used for energy supply during outdoor work and survival, providing a new idea for the design of outdoor energy equipment.

Abstract Objective This study analyzes the safety and efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) treatments for Stage III Kummell’s disease without neurological symptoms, comparing the advantages and disadvantages of these two minimally invasive surgical methods. Methods A retrospective analysis was conducted on 53 patients with non-neurological Stage III Kummell’s disease treated with PVP and PKP at our hospital from December 2018 to January 2023. Patients were divided into PVP (25 cases) and PKP (28 cases) groups based on the surgical method. There were no significant differences in general preoperative data between the two groups (all p > 0.05), ensuring comparability. The study compared surgical duration, volume of bone cement injected, distribution pattern of bone cement, rate of bone cement leakage, and preoperative, postoperative, and final follow-up scores of Visual analogue scale(VAS) and Oswestry disability index(ODI). Additionally, relative anterior height of the injured vertebrae, and Cobb angle of deformity, along with their changes at preoperative, postoperative, and final follow-up stages were calculated and analyzed. Results No significant preoperative differences were observed between the groups (p > 0.05). The PKP group had longer surgeries, higher cement volumes (p 0.05) but improved significantly from preoperative (p 0.05). Conclusion The study evaluates the safety and efficacy of PVP and PKP for Stage III Kummell’s disease without neurological symptoms, comparing the merits of both minimally invasive techniques.

Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.

Surface cracks in gun bore may exacerbate rifling ablation and wear and in turn shorten barrel life. Thermomechanical coupling finite element (FE) models of bore are established and the dynamic responses of the bore under high-temperature and high-pressure are numerically simulated. The stress distribution characteristics on the inner surface are analyzed and the effects of autofrettage, number of firings and harden layer on the stress distribution are discussed. Based on the stress distribution characteristics, FE models with two initial cracks on the ledge of land surface are set up and the propagation, interaction and intersection of the cracks are numerically simulated, considering the effect of the distance between the two cracks. Based on simulation results, the initiation and propagation pattern and mechanism of the cracks on the inner surface are analyzed. An ablation test system was designed and produced, and used to experimentally verify the initiation and propagation mechanism of the cracks. The observed crack patterns on the inner surface of a real gun bore are also used to illustrate the mechanism obtained in this work. Understanding of the initiation and propagation mechanism of cracks in gun bore can be applied to improve and optimize the design of barrels.

The purpose of this study is to investigate the risk factors for postoperative deep vein thrombosis (DVT) in patients with traumatic spinal fractures complicated with Spinal Cord Injury(SCI). We conducted a retrospective analysis of 110 patients with traumatic spinal fractures and SCI admitted to our hospital from March 2021 to April 2024. DVT was diagnosed using ultrasound. Patient history, general data, surgical data, laboratory tests, and thromboelastogram (TEG) results were collected. The patients were divided into a DVT group and a non-DVT group according to the results of ultrasound one week after surgery. The risk factors and diagnostic value were analyzed using binary logistic regression and receiver operating characteristic (ROC) curves in both univariate and multivariate analyses. Multivariate and ROC analysis results showed that D-dimer, lower extremity, duration of bedrest, and MA values of TEG were independent risk factors for DVT in SCI, with D-dimer having the highest diagnostic value (AUC = 0.883). The AUC values for lower extremity, duration of bedrest, and MA were 0.731, 0.750, and 0.625. In conclusion, Postoperative D-dimer > 5.065 mg/l, lower extremity

[Objective] In the inaugural switching operation between Pipelines Q1 and Q2, which were originally used for heated and normaltemperature transmission of crude oil respectively in China, the approach of “transformation while operation” was employed, posing challenges such as complex process flows, demanding engineering implementation, and engagement of numerous offload and injection users. [Methods] To ensure a rational transformation and switching mode with minimal impact on normal production and operation, a comprehensive study was conducted on the hydraulic and thermal systems of these transmission pipelines. This study aimed to evaluate various factors influencing preheating and temperature dropping during commissioning, as well as the pros and cons of different switching modes. Simulation accuracy was checked for the preheating process after transforming Pipeline Q2, originally designed for normaltemperature transmission, into a heated transmission system. These simulation results were then verified with actual engineering data to ensure alignment with the practical requirements. Additionally, valuable field experience was gained from the transformation of Pipeline Q1, originally intended for heated transmission, into a normal-temperature transmission system. Based on these study findings, reasonable suggestions and recommendations were presented for key nodes in switching operations. [Results] The selection of the preheating method should be based on site-specific conditions when transforming in-service normal-temperature oil transmission pipelines into heated transmission systems. For instance, Pipeline Q2 should be treated by heating Russian oil to be transmitted in advance combined with preheating the pipeline with high-temperature Russian oil, aligning the commissioning process with the transmission requirements of Daqing oil.Likewise,appropriate measures should be taken to gradually reduce the temperature of oil products between stations during the transition from the heated to normal-temperature mode.This can be achieved through the quantitative transmission of oil products with a gradually decreasing temperature by batch.To facilitate this,heating stations along the route can be utilized to ensure a gradual temperature drop of the oil products between stations. [Conclusion] The study findings offer valuable insights for commissioning under switching operations of inservice crude oil pipelines.

Distilled grain waste (DGW) is rich in nutrients and can be a potential resource as animal feed. However, DGW contains as much as 14% lignin, dramatically reducing the feeding value. White-rot fungi such as Pleurotus ostreatus could preferentially degrade lignin with high efficiency. However, lignin derivatives generated during alcohol distillation inhibit P. ostreatus growth. Thus, finding a new strategy to adjust the DGW properties to facilitate P. ostreatus growth is critical for animal feed preparation and DGW recycling. In this study, three dominant indigenous bacteria, including Sphingobacterium thermophilum X1, Pseudoxanthomonas byssovorax X3, and Bacillus velezensis 15F were chosen to generate single and compound microbial inoculums for DGW composting to prepare substrates for P. ostreatus growth. Compared with non-inoculated control or single microbial inoculation, all composite inoculations, especially the three-microbial compound, led to faster organic metabolism, shorter composting process, and improved physicochemical properties of DGW. P. ostreatus growth assays showed the fastest mycelial colonization (20.43 μg·g−1 ergosterol) and extension (9 mm/d), the highest ligninolytic enzyme activities (Lac, 152.68 U·g−1; Lip, 15.56 U·g−1; MnP, 0.34 U·g−1; Xylanase, 10.98 U·g−1; FPase, 0.71 U·g−1), and the highest lignin degradation ratio (30.77%) in the DGW sample after 12 h of composting with the three-microbial compound inoculation when compared to other groups. This sample was relatively abundant in bacteria playing critical roles in amino acid, carbohydrate, energy metabolism, and xenobiotic biodegradation, as suggested by metagenomic analysis. The feed value analysis revealed that P. ostreatus mycelia full colonization in composted DGW led to high fiber content retention and decreased lignin content (final ratio of 5% lignin) but elevated protein concentrations (about 130 g·kg−1 DM). An additional daily weight gain of 0.4 kg/d was shown in cattle feeding experiments by replacing 60% of regular feed with it. These findings demonstrate that compound inoculant consisting of three indigenous microorganisms is efficient to compost DGW and facilitate P. ostreatus growth. P. ostreatus decreased the lignin content of composted DGW during its mycelial growth, improving the quality of DGW for feeding cattle.

AP000695.2 is a novel long non-coding RNA (lncRNA). Its aberrant high expression is remarkably associated with poor prognosis of patients with lung adenocarcinoma (LUAD). However, its role and underlying mechanism in LUAD remains unclear. Previous bioinformatics analysis indicated that AP000695.2 may be closely related to the glycolysis of LUAD. This study aims to verify and explore the mechanism of AP000695.2 in glycolysis of LUAD. Overexpression plasmid and siRNA are used to construct cell models of upregulation and downregulation of AP000695.2, respectively. AP000695.2 is highly expressed in lung cancer cell lines as revealed by qPCR. Western blot analysis, FDG uptake, lactate production assay and ECAR determination results show that high expression of AP000695.2 facilitates glycolysis of LUAD cells. CCK-8, EdU staining, Transwell and wound healing assays show that high expression of AP000695.2 promotes cell growth and migration of LUAD. The relationship between AP000695.2 and miR-335-3p is confirmed by bioinformatics analysis and dual-luciferase reporter assays. Through the dual-luciferase reporter assay, TEA domain transcription factor 1 (TEAD1) is identified as a target gene of miR-335-3p. Rescue experiments are applied to verify the relationship among AP000695.2, miR-335-3p and TEAD1. Our study indicates that AP000695.2 is involved in the mechanism of LUAD through functioning as a ceRNA to competitively sponge miR-335-3p, thereby regulating the expression of TEAD1. In the in vivo models, AP000695.2 depletion restrains tumor growth and glycolysis. AP000695.2 promotes the glycolysis of LUAD by regulating the miR-335-3p/TEAD1 axis, and it may serve as a potential target of anti-tumor energy metabolism therapy.

D-p-hydroxyphenylglycine (D-HPG) is an important intermediate for the synthesis of sweeteners and drugs. An innovative continuous chromatographic process was developed to recover D-HPG from crystallization mother liquor, with the aim of reducing the process cost and improving the quality of D-HPG. The thickening properties of different nanofiltration membranes on mother liquor were investigated by pre-treatment test, and the Applexion NF200 nanofiltration membrane was selected to enrich D-HPG. The separation properties of different resins were analyzed by single column experiment, and the separation degree of Applexion XA945 resin to D-HPG and ammonium sulfate could reach 16. Based on the results, the way of sequential simulated moving bed separation was further studied. The results showed that after separation by the sequential simulated moving bed, the average purity of D-HPG in feeding was increased from 42.2% to 96.3%, and the average yield was 91%. The continuous chromatographic system is a promising method for the recovery of D-HPG from crystallization mother liquor. Compared with the traditional process, the new process not only ensures the total yield of D-HPG, but also greatly reduces the process cost and improves the product quality.

[Purpose/Significance] The online interaction of participatory websites improves the efficiency of information transmission and communication, and improves users' perception and experience. Through the study of bullet screen under participatory website, it complements the relevant research on user experience theory, and provides practical guidance for short video disseminators and relevant participatory websites. [Method/Process] This paper selected Bilibili, a typical participatory website, as the research object, took the short video bullet screen data and aggregated hotness indicator data of Bilibili as the research samples to study its user interaction experience, used python to crawl bullet screen popularity and content information of short videos, and studied its users’ aggregated hotness indicators and user generated contents of participatory websites through correlation analysis and text emotion analysis. [Result/Conclusion] The results show that there is a correlation between the number of bullet screen, the number of comments and the number of the video playback of participatory websites; Real time bullet screen interaction enhances the audience's cognitive sharing, emotional experience and onlooker experience.

Huge hazards are frequently caused by earthquake-induced rock avalanche. The study of dynamic response characteristics and failure mechanism of the rock slope in specific geological condition is a challenging issue in geotechnical engineering. In this paper, a shaking table test that reproduces the Shuiqiuchi rock avalanche was carried out to understand the dynamic response and failure mechanism of rock slope controlled by faults. The testing results show that when the dip angle of the fault is greater than a specific critical angle, part of the reflected and transmitted waves at the discontinuous interface change into sliding waves, resulting in a sudden change in the acceleration response at the fault. The peak acceleration amplification factor inside the model slope presents a significant three-stage trend. Peak horizontal acceleration amplification factor increases obviously with elevation, while peak vertical acceleration amplification factor increases slightly with elevation. The natural frequency curve of the slope model can be divided into three stages with a downward trend, which indicates that the dynamic characteristics of the model have changed. By comparing the shaking table test with the Shuiqiuchi rock avalanche prototype, the main failure mode of the rock slope with fault structure is found as follows: the slope crest first shows vertical tensile cracks under the seismic load, followed by cracking damage of the fragmented rock mass in the hanging wall of the fault, and finally sliding occurs along the fault surface. This research could provide references for the early-warning of granite avalanche, and offer the basic data and scientific support for the development of Qinling Mountain geological heritages.

ObjectiveThis study aimed to investigate a new noninvasive traction method on the treatment of severe cervical kyphotic deformity.MethodsThe clinical data of patients with severe cervical kyphosis (Cobb > 40°) treated in Peking University Third Hospital from March 2004 to March 2020 were retrospectively summarized. 46 cases were enrolled, comprising 27 males and 19 females. Fifteen patients underwent skull traction, and 31 patients underwent suspensory traction. Among them, seven used combined traction after one week of suspensory traction. Bedside lateral radiographs were taken every two or three days during traction. The cervical kyphosis angle was measured on lateral radiographs in and extended position at each point in time. The correction rate and evaluated Japanese Orthopedic Association (JOA) scoring for the function of the spinal cord were also measured. The data before and after the operation were compared with paired sample t-test or Wilcoxon signed-rank test.ResultsNo neurological deterioration occurred during the skull traction and the cervical suspensory traction. There were 12 patients with normal neurological function, and the JOA score of the other 34 patients improved from 11.5 ± 2.8 to 15.4 ± 1.8 at the end of follow up (P

Takayasu arteritis (TA) is a chronic granulomatous vasculitis involving in the main branches of aorta. Previous studies mainly used peripheral blood and some vascular tissues but seldom studies have sequenced vascular tissues. Here in this study, we aimed to explore the alterations of mRNA in TA by performing bulk RNA sequencing. A total of 14 abdominal aortic tissues including 8 from renal transplantation and 6 from patient with TA undergoing bypass surgeries. Bulk RNA sequencing were performed and after the quality control, a total of 1897 transcripts were observed to be significantly differently (p < 0.05 and Log2FC > 1) expressed between the TA and control group, among which 1,361 transcripts were in TA group and 536 in the Control group. Reactome Pathway Enrichment Comparison analysis revealed interleukin-10 signaling and signaling by interleukins were highly expressed in TA group. Besides, extracellular matrix organization was also observed in this group. WGCNA and PPI obtained 26 core genes which were highly correlated with the clinical phenotype. We then also perform deconvolution of the bulk RNA-seq data by using the scRNA-seq dataset and noticed the high proportion of smooth muscle cells in our dataset. Additionally, immunohistochemical staining confirmed our bioinformatic analysis that TA aortic tissues express high levels of IL-1R1 and IL-1R2. Briefly, this study revealed critical roles of interleukins in TA pathogenesis, and SMCs may also participate in the reconstruction in vessel wall at late stage of TA.

Zhuo Li,1– 3,* La-Xiu Li,3,4,* Yan-Jun Diao,3 Juan Wang,3 Yun Ye,1,3 Xiao-Ke Hao2,3,5 1Department of Laboratory Medicine, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi 710077, People’s Republic of China; 2The National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of China; 3Department of Laboratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China; 4Department of Laboratory Medicine, Xi’an Fourth Hospital, Xi’an, Shaanxi 710004, People’s Republic of China; 5School of Medicine, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Ke HaoSchool of Medicine, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of ChinaEmail haoxkg@126.comBackground: Novel and non-invasive biomarkers with higher sensitivity and specificity for the diagnosis of prostate cancer (PCa) is urgently needed. In this study, we used next-generation sequencing (NGS) to characterize the genome-wide exosomal miRNA expression profiling in urine specimens and explored the diagnostic potential of urinary exosomal miRNAs for PCa.Methods: Urinary exosomal microRNA expression profiling was performed by next-generation sequencing (NGS) and then validated by quantitative real-time PCR.Results: Significant downregulation of urinary exosomal miR-375 was observed in PCa patients compared with healthy controls, while the expression levels of urinary exosomal miR-451a, miR-486-3p and miR-486-5p were found to be significantly up-regulated in the PCa patients. Furthermore, the expression level of urinary exosomal miR-375 showed a significant correlation with the clinical T-stage and bone metastasis of patients with PCa (P< 0.05). Receiver operator characteristic curve demonstrated that the urinary exosomal miR-375, miR-451a, miR-486-3p and miR-486-5p levels can be used to differentiate PCa patients from healthy controls, with area under the curves (AUCs) of 0.788, 0.757, 0.704 and 0.796, respectively. The urinary exosomal miR-375 was found to be superior in discriminating between localized and metastatic PCa with an AUC of 0.806. Moreover, PCa patients can be distinguished from patients with benign prostatic hyperplasia by using a panel combining urinary exosomal miR-375 and miR-451a with an AUC of 0.726.Conclusion: These findings demonstrate that the urinary exosomal miRNAs can serve as novel and non-invasive biomarkers for diagnosing and predicting the progression of PCa.Keywords: prostate cancer, next-generation sequencing, urinary, exosomal miRNAs

De-Ming Zhao,1 Yu-E Diao,2 Qing Xu3 1Department of Gastrointestinal Surgery, Dalian Municipal Central Hospital, Dalian, People’s Republic of China; 2Department of General Surgery, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 3Department of Anorectal Surgery, Nantong Third People’s Hospital, Nantong University, Nantong, Jiangsu, People’s Republic of ChinaCorrespondence: Qing Xu Tel/Fax +86-513-89093902Email qing19xu@sina.comBackground: Studies show that MDM4 may play a pivotal role in colorectal cancer (CRC). Recently, a host of studies suggest that MDM4 gene rs4245739 polymorphism may modify the risk of different cancers.Methods: In this study, we were interested whether MDM4 gene rs4245739 polymorphism correlated with the risk and clinical characteristics of CRC. Logistic regression was adopted to estimate the association of rs4245739 polymorphism and CRC risk.Results: We enrolled 444 CRC patients and 530 controls and found MDM4 gene rs4245739 polymorphism may decrease the risk of CRC. Stratified analyses uncovered that this variant was connected to a less risk of CRC in females, non-drinkers, non-smokers, and people under 60 years old. Additionally, rs4245739 polymorphism was related to TNM staging, pathological type, tumor size, and location of CRC. Furthermore, this polymorphism was significantly linked with the survival of CRC.Conclusion: Totally, this study suggests that MDM4 rs4245739 polymorphism is linked with the risk and clinical characteristics of CRC.Keywords: MDM4, colorectal cancer, case–control study, rs4245739, polymorphism

Cheng-Cheng Zhang1 ,* Cheng-Wu Zhang2 ,* Hao Xing3 ,* Yu Wang4 ,* Lei Liang2,5 ,* Yong-Kang Diao2,5 ,* Ting-Hao Chen,6 Wan Yee Lau,3,7 Ping Bie,8 Zhi-Yu Chen,1 Tian Yang1,3 1Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China; 2Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, China; 3Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China; 4Department of Hepatobiliary Surgery, Chongqing University Cancer Hospital, Chongqing, China; 5Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China; 6Department of General Surgery, Ziyang First People’s Hospital, Sichuan, China; 7Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; 8Department of Hepatobiliary, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, China*These authors contributed equally to this workCorrespondence: Zhi-Yu ChenDepartment of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30, Gaotanyan Street, Chongqing 400038, ChinaEmail chenzhiyu_umn@163.comTian YangDepartment of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai 200438, ChinaEmail yangtian6666@hotmail.comBackground: A normal albumin-to-globulin ratio (NAGR) in serum is greater than 1. Inversed albumin-to-globulin ratio (IAGR < 1) indicates poor synthetic liver function or malnutrition. The aim of this study is to evaluate whether preoperative IAGR was associated with worse oncologic survival after hepatectomy for hepatocellular carcinoma (HCC).Patients and Methods: Patients who underwent curative hepatectomy for HCC between 2009 and 2016 in four centers were divided into the IAGR and NAGR groups based on their preoperative levels, and their clinical characteristics and long-term survival outcomes were compared. Univariable and multivariable Cox regression analyses were performed to identify risk factors of overall survival (OS) and recurrence-free survival (RFS).Results: Of 693 enrolled patients, 136 (19.6%) were in the IAGR group. Their 5-year OS and RFS rates were 31.6% and 21.3%, respectively, which were significantly worse than the NAGR group (43.4% and 28.7%, both P < 0.001). The area under the receiver operating characteristic curves in predicting 5-year OS and RFS using the albumin-to-globulin ratio were 0.68 and 0.67, respectively, which were significantly higher than albumin (0.60 and 0.59), globulin (0.56 and 0.57), Child-Pugh grading (0.61 and 0.60), Model for End-Stage Liver Disease Score (0.59 and 0.58), and Albumin-Bilirubin grading (0.64 and 0.63). Multivariable analyses identified that preoperative IAGR was independently associated with worse OS (HR: 1.444, 95% confidence interval (CI): 1.125– 1.854, P = 0.004) and RFS (HR: 1.463, 95% CI: 1.159– 1.848, P = 0.001).Conclusion: Preoperative IAGR was useful in predicting worse OS and RFS in patients who underwent curative hepatectomy for HCC.Keywords: hepatocellular carcinoma, hepatectomy, albumin, globulin, survival, recurrence

Zheng-Liang Chen,1,* Cheng-Wu Zhang,2,* Lei Liang,2,* Han Wu,3,* Wan-Guang Zhang,4 Yong-Yi Zeng,5 Wei-Min Gu,6 Ting-Hao Chen,7 Jie Li,8 Yao-Ming Zhang,9 Hong Wang,10 Ya-Hao Zhou,11 Chao Li,2 Yong-Kang Diao,2 Wan Yee Lau,3,12 Meng-Chao Wu,3 Feng Shen,3 Tian Yang,3 Ying-Jian Liang1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, People’s Republic of China; 2Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, People’s Republic of China; 3Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital (Navy Medical University), Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Hepatic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, People’s Republic of China; 6The First Department of General Surgery, The Fourth Hospital of Harbin, Heilongjiang, People’s Republic of China; 7Department of General Surgery, Ziyang First People’s Hospital, Sichuan, People’s Republic of China; 8Department of Hepatobiliary Surgery, Fuyang People’s Hospital, Anhui, People’s Republic of China; 9The 2nd Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Guangdong, People’s Republic of China; 10Department of General Surgery, Liuyang People’s Hospital, Hunan, People’s Republic of China; 11Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Yunnan, People’s Republic of China; 12Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, SAR, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying-Jian LiangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Road, Heilongjiang 150006, People’s Republic of ChinaEmail genomeliang@hotmail.comTian YangDepartment of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai 200438, People’s Republic of ChinaEmail yangtiandfgd@hotmail.comBackground: With an increase in life expectancy and improvement of surgical safety, more elderly patients with hepatocellular carcinoma (HCC), even with large tumors, are now considered for hepatectomy. This study aimed to clarify the impact of age on short- and long-term outcomes after major hepatectomy (≥ 3 segments) for large HCC (≥ 5 cm).Patients and Methods: Using a multicenter database, patients who underwent curative-intent major hepatectomy for large HCC between 2006 and 2016 were identified. Postoperative morbidity and mortality, overall survival (OS) and recurrence-free survival (RFS) were compared between the elderly (≥ 65 years) and younger (< 65 years) patients. Univariable and multivariable Cox-regression analyses were performed to identify the risk factors of OS and RFS in the entire and elderly cohorts, respectively.Results: Of 830 patients, 92 (11.1%) and 738 (88.9%) were elderly and younger patients, respectively. There were no significant differences in postoperative 30-day mortality and morbidity between the two groups (5.4% vs 2.6% and 43.5% vs 38.3%, both P> 0.05). The 5-year OS and RFS rates in elderly patients were also comparable to younger patients (35.0% vs 33.2% and 20.0% vs 20.8%, both P> 0.05). In the entire cohort, multivariable Cox-regression analyses identified that old age was not independently associated with OS and RFS. However, in the elderly cohort, preoperative alpha-fetoprotein level > 400 μg/L, multiple tumors, macrovascular invasion and microvascular invasion were independently associated with decreased OS and RFS.Conclusion: Carefully selected elderly patients benefited from major hepatectomy for large HCC as much as younger patients, and their long-term prognosis was determined by preoperative alpha-fetoprotein level, tumor number and presence of macro- or micro-vascular invasion.Keywords: hepatocellular carcinoma, hepatectomy, survival, recurrence, elderly

Shu-Chen Chen,1 Yu-Zhu Diao,1 Zi-Han Zhao,2 Xiao-Ling Li1 1Medical Oncology Department of Thoracic Cancer 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, Liaoning 110042, People’s Republic of China; 2The Second Clinical College of Dalian Medical University, Dalian, Liaoning 116044, People’s Republic of ChinaCorrespondence: Xiao-Ling LiMedical Oncology Department of Thoracic Cancer 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, No. 44, Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, People’s Republic of ChinaTel/Fax +86-24-31916361Email lixiaoling_med@163.comBackground: Lung cancer has the highest incidence among solid tumors in men and is the third most common cancer in women. Despite improved understanding of genomic and mutational landscape in non-small cell lung cancer (NSCLC), the five-year survival in these patients has remained stagnant at a dismal 15%. The first line of treatment commonly adapted for NSCLC patients with somatic mutation in EGFR is tyrosine kinase inhibitor gefitinib or erlotinib. EGFR mutant cells seem to be intrinsically sensitive to tyrosine kinase inhibitors; however, the remaining 20– 30% patients are resistant to tyrosine kinase inhibitor.Materials and Methods: Here we show, using in vitro normal and NSCLS cell lines, that the lncRNA Prostate androgen-regulated transcript 1 (PART1) is expressed at higher levels in NSCLC cells compared to normal lung epithelial cell line, corroborating two earlier studies.Results: We additionally show that these cells are resistant to erlotinib which is reversed in some, but not all, cell lines following suppression of PART1 expression. The differential response to erlotinib following siRNA-mediated knockdown of PART1 was found to be related to the mutational status of KRAS. Only in cells with wild-type KRAS suppression of PART1 sensitized them to erlotinib. Knockdown of mutant KRAS did not sensitize those cell lines to erlotinib. But knockdown of mutant KRAS along with suppression of PART1 sensitized the cells to treatment with erlotinib. The results from the study reveal a yet undefined and important role of lncRNA PART1 in defining sensitivity to erlotinib. This action is mediated by mutation status of KRAS.Conclusion: Even though preliminary, our results indicate PART1 might be a potential candidate for targeted therapy or used as a predictor of chemosensitivity in patients with NSCLC.Keywords: lncRNA, PART1, KRAS, non-small cell lung cancer, chemosensitivity, erlotinib

Objectives: Takayasu Arteritis (TA) is a highly specific vascular inflammation and poses threat to patients’ health. Although some patients have accepted medical treatment, their culprit lesions require surgical management (TARSM). This study aimed at dissecting the transcriptomes of peripheral blood mononuclear cells (PBMCs) in these patients and to explore potential clinical markers for TA development and progression.Methods: Peripheral blood were collected from four TA patients requiring surgical management and four age-sex matched healthy donors. Single cell RNA sequencing (scRNA-seq) was adopted to explore the transcriptomic diversity and function of their PBMCs. ELISA, qPCR, and FACS were conducted to validate the results of the analysis.Results: A total of 29918 qualified cells were included for downstream analysis. Nine major cell types were confirmed, including CD14+ monocytes, CD8+ T cells, NK cells, CD4+ T cells, B cells, CD16+ monocytes, megakaryocytes, dendritic cells and plasmacytoid dendritic cells. CD14+ monocytes (50.0 vs. 39.3%, p < 0.05) increased in TA patients, as validated by FACS results. TXNIP, AREG, THBS1, and CD163 increased in TA patients. ILs like IL-6, IL-6STP1, IL-6ST, IL-15, and IL-15RA increased in TA group.Conclusion: Transcriptome heterogeneities of PBMCs in TA patients requiring surgical management were revealed in the present study. In the patients with TA, CD14+ monocytes and gene expressions involved in oxidative stress were increased, indicating a new treatment and research direction in this field.

Amorphophallus konjac (Araceae) a perennial herb, it has high medicinal and industrial value. In this study, a simple and efficient system for direct somatic embryogenesis and plantlet regeneration of Amorphophallus konjac was developed. The floral axis was used as the experimental material. The primary callus, developed from the floral axis grown on Murashige and Skoog (MS) medium supplemented with different hormone combination at different concentrations. The highest rate of embryogenic callus formation was observed on the MS medium containing 9.04 µM 2, 4-dichlorophenoxyacetic acid (2, 4-D) and 5.37 µM naphthalene acetic acid (NAA). The maximum induction rate was 79.8%, and the embryogenic calli were able to subculture on a medium containing similar hormone combination for over 1 year. The calli were also placed on different media for regeneration and it produced complete plants with shoots and root systems simultaneously. The highest differentiation rate of the embryogenic calli grown on differentiation medium supplemented with 8.88 µM 6-benzylaminopurine (6-BA) and 5.37 µM NAA was 95.6%. Flow cytometry analysis showed no ploidy variation in all the regenerate plantlets.

The 6- DOF joint robot with offset wrist can’t satisfy the Pieper rule,thus there are no closed- form inverse kinematics solutions for them. Compared with non- offset robot,a numerical iterative algorithm that integrates the closed- form inverse solutions of non- offset robot with the modified Newton iteration method is obtained,and the inverse method is utilized to obtain the closed- form inverse solutions of the non- offset robot with the same configurations,and the solutions are considered as the initial values of the subsequent iteration. According to the forward kinematics,by combining the three components of position vector with the three independent elements of attitude matrix,a non- liner equation set which contains all joint variables can be obtained,and then the numerical inverse kinematics solutions for the robot with offset wrist can be searched with the modified Newton iteration method. A large number of tests indicate that the algorithm can meet the requirements of real- time control.

To investigate the preparation of radioiodinated Chlorpyrifos and its biodistribution in mice, Chlorpyrifos was labeled with 131I using the Iodogen method. Biodistribution studies were carried out in KM mice. At different times after radiopharmaceutical i.v. administration (185 kBq 131I-Chlorpyrifos/mouse, n=5), the animals were sacrificed. Blood samples and the tissues of interested were collected, weighted and counted. The percentage of injected does per gram (%ID/g) was calculated for each sample. The labeling yield of 131I-Chlorpyrifos was 93.5%, The radiochemical purity (RCP) was 96.9%. Biodistribution in mice demonstrated that 131I-Chlorpyrifos was extensive, and the uptakes mainly occur in lung, stomach, small-intestine, colon, musle, and submaxillay gland, as indicated by their amount of 37.12%ID/g, 6.18%ID/g, 8.12%ID/g, 8.15%ID/g, 7.04%ID/g, and 7.02%ID/g at 10 min, respectively. And it was metabolized in liver and kidney, as indicated by their uptake of 4.34%ID/g and 8.50%ID/g at 5 min, and 0.22%ID/g and 0.69%ID/g at 4 h, respectively. In addition, 131I-Chlorpyrifos was cleared out from blood quickly, and the uptake of 131I-Chlorpyrifos in blood was 37.27%ID/g at 5 min, and decreased to 1.35%ID/g at 4 h post injection. In conclusion, 131I-Chlorpyrifos was stable in vitro and it was absorbed in lung and digestive tract, and it was metabolized mainly in liver and kidney, worthy of further investigation to trace the compound in vivo and in vitro.

The Monte Carlo method is a simple and common way to analyze workspace for robot,and workspace boundary extraction is the key part of Monte Carlo workspace analysis. By using an improved algorithm to extract the workspace boundary of a robot with 7 degrees of freedom,the extraction efficiency and the result both meet the requirement of the following work. The efficiency and accuracy of the improved algorithm are analyzed through experiment,and the result shows the improved algorithm is effective.

In view of problem of single-point failure in hardware and software running environment of gas disaster early-warning system of coal mine, a gas disaster early-warning system based on hot-standby was proposed, and its hot-standby solution, hardware and software design and implementation were introduced. The system employs high-reliability hot-standby cluster for mutual backup and hot-standby solution based on RoseHA and shared disc array, greatly improves its reliability. The application result shows that availability of the gas disaster early-warning system based on hot-standby is greatly improved with longer mean time between failures and shorter mean time for fixing failure, compared with the early-warning system based on single server.

Wen-Hong Xu,1 Min Han,2 Qi Dong,3 Zhi-Xuan Fu,3 Yuan-Yuan Diao,2 Hai Liu,3 Jing Xu,3 Hong-Liang Jiang,4 Su-Zhan Zhang,3 Shu Zheng,3 Jian-Qing Gao,2 Qi-Chun Wei11Department of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 2Institute of Pharmaceutics, College of Pharmaceutical Sciences, 3Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, 4Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, ChinaBackground: The purpose of this study is to evaluate the efficacy of composite doxorubicin-loaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line.Methods: A novel composite doxorubicin-loaded micelle consisting of polyethylene glycol-polycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems.Results: Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin.Conclusion: Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer.Keywords: doxorubicin, lung cancer, micelles, radiosensitivity, spheroids

Yuan-Yuan Diao1,2,*, Hao-Ying Li3,*, Ying-Hua Fu4, Min Han1, Yu-Lan Hu1, Hong-Liang Jiang5, Yasuo Tsutsumi6, Qi-Chun Wei7, Da-Wei Chen2, Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang; 3Biomanufacturing Research Centre, Department of Mechanical and Electrical Engineering, Soochow University, Suzhou; 4Department of Pharmaceutics, Jiaxing University College of Medicine, Jiaxing; 5Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People's Republic of China; 6Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan; 7Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, People's Republic of China, *These authors contributed equally to this workBackground: Multidrug resistance remains a major obstacle to successful cancer chemotherapy. Some chemical multidrug resistance inhibitors, such as ciclosporin and verapamil, have been reported to reverse resistance in tumor cells. However, the accompanying side effects have limited their clinical application. In this study, we have developed a novel drug delivery system, ie, a polyethyleneglycol-polycaprolactone (PEG-PCL) copolymer micelle encapsulating doxorubicin, in order to circumvent drug resistance in adriamycin-resistant K562 tumor cells.Methods: Doxorubicin-loaded diblock copolymer PEG-PCL micelles were developed, and the physicochemical properties of these micelles, and accumulation and cytotoxicity of doxorubicin in adriamycin-resistant K562 tumor cells were studied.Results: Doxorubicin-loaded micelles were prepared using a solvent evaporation method with a diameter of 36 nm and a zeta potential of +13.8 mV. The entrapment efficiency of doxorubicin was 48.6% ± 2.3%. The micelles showed sustained release, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells.Conclusion: This study suggests that PEG-PCL micelles have the potential to reverse multidrug resistance in tumor cells.Keywords: doxorubicin, polyethylene glycol, polycaprolactone, adriamycin-resistant K562 tumor cells, multidrug resistance, micelles

Based on field data of polycyclic aromatic hydrocarbons (PAHs) in water and sediment in Nansi Lake. The concentrations and the partitioning characteristic of PAHs in the water and sediment were studied. The lgKd of high molecular weight PAHs were higher than the low molecular weight PAHs. The most of PAHs Kd values were negligible correlated with TOC, soluble salt, clay and pH of the sediment in Nansi Lake.

In this study, an efficient and reproducible plant regeneration system for lotus (Nelumbo nucifera Gaertn.) was established using shoot apical meristems from the buds and one-week-old aseptically germinated embryos as explants. Multiple shoot clumps were induced on Murashige and Skoog (MS) basal medium supplemented with various combinations of N6-Benzylaminopurine (6-BA) and α-Naphthalene acetic acid (NAA). The maximum response was obtained with 2.22 μM 6-BA, and produced 21.33 shoots per explant after four weeks. After five subcultures, multiple shoot clumps were transferred to MS basal medium supplemented with various combinations of 3-Indolebutyric acid (IBA), NAA and sucrose for root induction. After four weeks, plantlets with well-developed roots were achieved on MS basal medium supplemented with 0.54 μM NAA and 30 g/L sucrose with 100% rooting rate. The successfully acclimated plantlets were transferred to pots with the addition of 2 g/L KMnO4 into the soils, and finally fertile plants with much bigger leaves were obtained in the greenhouse. The survival rate was 97.33%.

Gel point is an important parameter of the safe pipeline transportation of the waxy crude oil, and predicting the gel point of the mixed crude oil quickly and precisely has a certain practical significance for this kind of mixed transportation. By adopting the scientific evaluation method of the prediction model, the adaptation of the Model Li Chuangwen, Model Liu Tianyou I, Model Liu Tianyou II, and Model Chen Jun to predicting the gel point of mixed crude oil transported in a certain pipeline is analyzed and compared, by which the most appropriate model for the prediction of the mixed crude oil is confirmed. It is found that Model Liu Tianyou I is most suitable for the mixed crude oil. Therefore, from the engineering point of view, for the mixed crude oil mentioned in this text, the gel point calculated by Model Liu Tianyou I has a certain reference value.

C5H4Br2N2, monoclinic, P21/n (no. 14), a = 6.07(1) Å, b = 10.53(2) Å, c = 11.89(2) Å, β = 104.49(3)°, V = 736.0 Å3, Z = 4, Rgt(F) = 0.0307, wRref(F2) = 0.0795, T = 296 K.

Abstract Background Cyclooxygenase-2(COX-2) promotes carcinogenesis, tumor proliferation, angiogenesis, prevention of apoptosis, and immunosuppression. Meanwhile, COX-2 over-expression has been associated with tumor behavior and prognosis in several cancers. This study investigated the antitumor effects of the selective COX-2 inhibitor, Celecoxib, on breast cancer in vitro and in vivo. Methods Human breast cancer MCF-7 and MDA-MB-231 cells were cultured with different concentration (10, 20, 40 μmol/L) of celecoxib after 0-96 hours in vitro. MTT assay was used to determine the growth inhibition of breast cancer cells in vitro. The expression of COX-2 on mRNA was measured by real-time quantitive PCR analysis. Flow cytometry was performed to analyze the cell cycle of MCF-7 cells. Levels of PGE2 were measured by ELISA method. The in vivo therapeutic effects of celecoxib were determined using rat breast cancer chemically induced by 7,12-dimethylben anthracene (DMBA). Results The inhibition of proliferation of both MCF-7 and MDA-MB-231 cells in vitro by celecoxib was observerd in time and dose dependent manner. Celecoxib effectively down-regulated the expression of COX-2. The cell cycle was arrested at G0/G1, and rate of cells in S phase was obviously decreased. Levels of PGE2 were inhibited by Celecoxib. The tumor incidence rate of the celecoxib group was lower than that of the control group. In addition, the tumor latency period of the celecoxib group was longer than that of the control group. Conclusions Celecoxib inhibited the proliferation of breast cancer cell lines in vitro, and prevented the occurrence of rat breast cancer chemically induced by DMBA. Therefore, celecoxib exhibits an antitumor activity and seems to be effective in anti-tumor therapy.

Abstract Background Inability to control autoimmunity is the primary barrier to developing a cure for type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem cells (CB-SCs) can control autoimmune responses by altering regulatory T cells (Tregs) and human islet β cell-specific T cell clones offers promise for a new approach to overcome the autoimmunity underlying T1D. Methods We developed a procedure for Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates lymphocytes from the whole blood and briefly co-cultures them with adherent CB-SCs before returning them to the patient's circulation. In an open-label, phase1/phase 2 study, patients (n = 15) with T1D received one treatment with the Stem Cell Educator. Median age was 29 years (range: 15 to 41), and median diabetic history was 8 years (range: 1 to 21). Results Stem Cell Educator therapy was well tolerated in all participants with minimal pain from two venipunctures and no adverse events. Stem Cell Educator therapy can markedly improve C-peptide levels, reduce the median glycated hemoglobin A1C (HbA1C) values, and decrease the median daily dose of insulin in patients with some residual β cell function (n = 6) and patients with no residual pancreatic islet β cell function (n = 6). Treatment also produced an increase in basal and glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3) did not exhibit significant change at any follow-up. Individuals who received Stem Cell Educator therapy exhibited increased expression of co-stimulating molecules (specifically, CD28 and ICOS), increases in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3 cytokine balance. Conclusions Stem Cell Educator therapy is safe, and in individuals with moderate or severe T1D, a single treatment produces lasting improvement in metabolic control. Initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of islet β cells. Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases without the safety and ethical concerns associated with conventional stem cell-based approaches. Trial registration ClinicalTrials.gov number, NCT01350219.

Abstract Background Tannins extracted from immature fruits of Terminalia chebula Fructus Retz. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects. Methods The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied. Results After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of Staphylococcus aureus and Klebsiella Pneumonia in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ. Conclusion The results suggest that tannin extracts from dried immature fruits of Terminalia chebula Fructus Retz. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts.