Search

Background Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody–drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020. Patients and methods We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2−) HR+/HER2− mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. Results Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%–45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7–12.7), median PFS was 5.5 months (95% CI 3.6–7.6), and median OS was 12 months (95% CI 9.0–18.2). Conclusions SG shows encouraging activity in patients with pretreated HR+/HER2− mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339). Trial registration ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552

We give an extension of Hua’s inequality for C*-valued norm in pre-Hilbert C*-modules setting. As its applications, some known and new generalizations of Hua’s inequality are deduced. In particular, we establish the connection between C*-valued norm triangle inequality and C*-valued norm Hua’s inequality. We also present some operator versions of Hua’s inequality on Hilbert spaces. As a consequence, we obtain various forms of Hua’s inequality. Moreover, we indicate that for our operator, Hua’s inequality is equivalent to operator convexity of a given continuous real function.

The difficulty of transanal total mesorectal excision (TME) is to find the correct dissection plane of perirectal space. As a complex new surgical procedure, the fascial anatomic landmarks of transanal approach operation are more likely to be ignored. It is often found that dissection plane is false after the secondary injury occurs during the operation, which results in the damage of pelvic autonomic nerves. Meanwhile, the mesorectum is easily damaged if the dissection plane is too close to the rectum. Thus, the safety of oncologic outcomes could be limited by difficulty achieving adequate TME quality. The promotion and development of the theory of perirectal fascial anatomy provides a new thought for researchers to design a precise approach for transanal endoscopic surgery. Transanal total mesorectal excision based on fascial anatomy offers a solution to identify the transanal anatomic landmarks precisely and achieves pelvic autonomic nerve preservation. In this paper, the authors focus on the surgical experience of transanal total mesorectal excision based on the theory of perirectal fascial anatomy, and discuss the feature of perirectal fascial anatomy dissection and technique of pelvic autonomic nerve preservation during transanal approach operation.经肛全直肠系膜切除术的难点在于寻找直肠周围间隙的正确分离平面，作为一种复杂的新术式，实施过程中经肛操作的筋膜解剖标志容易被忽略，待出现术中副损伤时才发现游离平面有误，从而导致盆腔自主神经受损；若是游离平面过于靠近直肠，可能造成直肠系膜受损，则无法实现完整的TME标本质量，从而导致肿瘤学安全无法得到保证。膜解剖理论的推动与发展，为经肛腔镜手术的精准实施提供了一种新的思路。基于膜解剖的经肛全直肠系膜切除术可精确识别经肛操作解剖标志并加以神经保护，为上述难题提供了一个解决方案。本中心以直肠周围筋膜解剖的理论为基础，结合经肛腔镜全直肠系膜切除手术经验，探讨经肛操作中直肠周围筋膜分离的特点和盆腔自主神经保护的技巧。.

Epidural catheters are often used in the provision of surgical anaesthesia and analgesia. These catheters need to be removed after a certain period, but difficulties may be encountered during this process. We present a case of difficult epidural catheter removal in an elderly woman who had undergone surgery for reduction and internal fixation of a comminuted intertrochanteric fracture at the left femur under combined spinal epidural anaesthesia. Anaesthesia was satisfactory during the operation; however, initial attempts to remove the catheter at the end of the procedure was met with significant resistance. Normal saline (5 ml) was injected through the catheter without difficulty, suggesting that the catheter was likely trapped and compressed but not obstructed. A nickel/titanium memory alloy suture was used as a guidewire to remove the catheter without damaging it. This case was analysed subsequently, and the management of future problematic removals is discussed herein. This article aims to raise awareness of, and to explore techniques for managing difficult epidural catheter removal.

Background This study evaluated the impact of the adapted version of the Respecting Choices® The Living Matters Advance Care Planning (ACP) facilitator training programme on trainees’ attitudes on facilitation 6 months post-training. Setting and participants Two hundred and twenty-one healthcare professionals consisting of doctors, nurses, medical social workers from different training venues in Singapore participated in the first phase of the study (pre- and post) of which 107 participated in the second phase 6 months later (follow-up). Methods Participants self-rated their attitudes, beliefs and behavioural intentions through surveys at three time points in an evaluation design that utilised repeated measures one-way ANOVA (pre-, post-, follow-up). Between-group differences were also examined using independent t-test. Results At follow-up, mean scores increased significantly in understanding, confidence, and competence. Changes in effect sizes were large. Although trainees continued to think that ACP is emotionally draining for facilitators, more than before, facilitation experience was considered pleasant for themselves with the positive change significant and moderate in effect size. Those who had experience completing/initiating ACP significantly held more positive views than those who did not. Conclusions The ACP facilitator training programme had lasting effects on enhancing the understanding, competence, and confidence of trainees. Importantly, findings showed that experience in actual facilitation within 6 months after training was important and giving trainees opportunities to facilitate is recommended.

Additional file 2. Post-course questionnaire.

Additional file 1. Pre-course questionnaire.

Additional file 3. Follow-up questionnaire.

Background Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. Patients and methods Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. Results In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). Conclusions SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.

Persistent trigeminal artery (PTA) originates from the posterior bend or lateral wall of the intra-cavernous carotid artery and is the most common occurring type of remnant primitive fetal arteries. In literature, there is limited number of reports on migraine-cephalgia (MC) associated with coexisting PTA. The primitive anastomose arteries that fully belong to the intracranial arterial vascular system are not supposed to perform any supportive functional activity; usually they are subjected to normal biological decay caused by the aging process and metabolic dysfunctions. The hypothesis suggests that these primitive fetal arteries such as PTA may not undergo a fast and structural deterioration but they might be active contributors to a series of mechanisms that can cause a variety of idiopathic complaints. Consequently this would bring a different therapeutic approach other than their surgical removal, which is the accepted option today as a solution for these problems. In this case report, a chronic unilateral MC due to coexisting PTA adjacent to trigeminal nerve is presented. The caliber and location of the PTA was confirmed by a CT-Angiography. The MC treatment was achieved by administration of bio-identical testosterone, human placenta extract (HPE), b-nicotinamide adenine dinucleotide (NADH) and low dose amlopidine.

Exosomes are small vesicles secreted by a variety of cell types under physiological and pathological conditions. When Saccharomyces cerevisiae are grown in low glucose, small vesicles carrying more than 300 proteins with diverse biological functions are secreted. Upon glucose addition, secreted vesicles are endocytosed that requires cup-shaped organelles containing the major eisosome protein Pil1p at the rims. We aim to identify genes that regulate the function of cup-shaped organelles in vesicle endocytosis. In cells lacking either VID27 or VID21, Pil1p distribution was altered and cup-shaped organelles became elongated with narrower openings. Change in shape reduced the number of vesicles in the deeper areas and impaired vesicle endocytosis. Vid21p and Vid27p were localized to vesicle clusters and interacted with other Vid proteins. In the absence of these genes, these vesicles failed to aggregate and were secreted. Vid21p and Vid27p are required for the aggregation and retention of vesicles that contain Vid proteins in the cytoplasm. Increased vesicles near the plasma membrane in mutant strains correlate with an increased Pil1p movement resulting in the fusion of cup-shaped organelles. We conclude that the shape of vesicle-containing organelles is critical for their functions in vesicle endocytosis.

1例以"注意力不集中"为主诉的9岁患儿表现为注意缺陷、认知功能损害、共济失调快速进展，结合临床表现、辅助检查及基因检测结果，诊断为肾上腺脑白质营养不良。该类患儿早期症状易与注意缺陷多动障碍混淆，儿科医师需注意鉴别。.

Due to the changing nature of power systems-with reduced electrical inertia and the prevalence of smaller controllable power resources rather than large generators-new control approaches are required to mitigate disturbances. Ubiquitous measurements and communications networks can be leveraged to accelerate and provide a targeted, real-time response in such future systems. However, autonomous control of power systems requires dependable measurements. This paper provides a review of state of the art approaches to real-time power system control using synchrophasor measurements. In particular, examples are given involving recent developments in frequency regulation. Through a case study, it is shown how laboratories can be linked using Software-Defined Networking technologies to conveniently share resources in order to realistically and comprehensively validate synchrophasor-based control systems.

Long-term continuous measurements of speciated atmospheric mercury were conducted from July 2013 to June 2014 in Hefei, a midlatitude inland city in eastern central China that experiences frequent haze pollution. The mean concentrations (±standard deviation) of gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM) and particle-bound mercury (PBM) were 3.95 ± 1.93 ng m−3, 2.49 ± 2.41 and 23.3 ± 90.8 pg m−3, respectively, on non-haze days, and 4.74 ± 1.62 ng m−3, 4.32 ± 8.36 and 60.2 ± 131.4 pg m−3, respectively, on haze days. Potential source contribution function (PSCF) analysis suggested that atmospheric mercury pollution on haze days was caused primarily by local emissions, instead of via long-range transport. The poorer mixing conditions on haze days also favored the accumulation of atmospheric mercury. Compared to GEM and GOM, PBM was especially sensitive to haze pollution. The mean PBM concentration on haze days was 2.5 times that on non-haze days due to elevated concentrations of particulate matter. PBM also showed a clear seasonal trend; its concentration was the highest in fall and winter, decreased rapidly in spring and was the lowest in summer, following the same order in the frequency of haze days in different seasons. On both non-haze and haze days, GOM concentrations remained low at night, but increased rapidly just before sunrise, which could be due to diurnal variation in air exchange between the boundary layer and free troposphere. However, non-haze and haze days showed different trends in daytime GEM and GOM concentrations. On non-haze days, GEM and GOM declined synchronously through the afternoon, probably due to the retreat of the free tropospheric air as the height of the atmospheric boundary layer increases. In contrast, on haze days, GOM and GEM showed opposite trends with the highest GOM and lowest GEM observed in the afternoon, suggesting the occurrence of photochemical oxidation. This is supported by simple box-model calculations, which showed that oxidation of GEM to GOM does occur and that the transport of free tropospheric GOM alone is not large enough to account for the observed increase in daytime GOM. Our results further postulate that NO2 aggregation with the HgOH intermediate may be a potential mechanism for the enhanced production of GOM during daytime.

During the crack propagation, crack tip contains stress odd singularity and has specific yield range. As the cycling loading continuing, the crack grows in the plastic zone. So the plastic zone is crucial to crack propagation action. In this paper, the crack propagation route was observed in different microstrctures, the deformation characteristic of plastic zone was analyzed for equiaxed structure and lamellar structure. The results show that crack propagation path is more straighter in equiaxed structure than that in lamellar structure. There were more tiny cracks near the crack surface in the lamellar structure during the crack growth, which shows that lamellar structure has a bigger plastic zone during the deformation.The plastic deformation need absorb the energy, which hinders the crack propagation.

BACKGROUND: The highly efficient production of parthenogenetic embryos from vitrified porcine in vitro matured oocytes has become essential for biotechnology and biomedicine research.To investigate the survival and parthenogenetic development of oocytes vitrified before or after electric activation.The vitrified oocytes were parthenogenetically activated at 0, 0.5, 1, 2 and 4 h post warming (h.p.w.), and fresh oocytes were vitrified at 0, 0.5, 1, 2 and 4 h post electric activation (h.p.a.).In comparison with non-vitrified oocytes, the rates of survival and activation of oocytes vitrified at 0.5, 1, 2 and 4 h.p.a. were similar, but the parameters in other vitrified groups significantly decreased. Parthenogenetic development in vitrified 0.5, 1, 2 and 4 h.p.a. groups was also significantly higher than that in other vitrified groups. Moreover, the total cell numbers of blastocysts were similar among all groups.Porcine oocytes vitrified at 0.5-4 h h.p.a. showed acceptable survival and pronuclear formation, and a higher blastocyst yield could be obtained from these oocytes.

This investigation reports a novel room-temperature camphene-based freeze-casting method to prepare aligned and porous alumina ceramics. The ceramic/camphene/dispersant mixed slurries were solidified using a fast room-temperature cooling installation to form excessively overgrown camphene dendrites. The experimental results revealed that camphene-based freeze casting could lead to formation of an aligned and porous structure through room-temperature cooling in a copper die. As the ceramic solid loading increased from 8 to 20 vol.-%, the total porosity of the sintered porous alumina ceramics ranged from 80·5 to 67·5% and the compressive strength increased from 5·8 to 23·5 MPa. This freeze-cast processing is considered potentially useful in fabricating novel porous ceramics with special structure.

A variety of stressors including alcohol (EtOH) are known to induce collagen production and fibrotic diseases. Matrix metalloproteinases (MMP) play an important role in regulating fibrosis, but little is known regarding the relationship between EtOH and MMPs. In addition, the signaling cascades involved in this process have not been elucidated. We have identified the MMP Adamts1 as a target of EtOH regulation. To characterize the function of Adamts1, we examined EtOH-induced alterations in collagen I and elastin protein levels in C2C12 myocytes. Incubation of myocytes with 100 mM EtOH decreased elastin and increased collagen content, respectively, and these changes were associated with increased O-GLcNAc modification of Adamts1. Conversely, silencing of Adamts1 by siRNA blocked the adverse effects of EtOH on collagen and elastin levels. Similar results were obtained after treatment with a pharmacological inhibitor of MMP. Changes in collagen were due, at least in part, to a decreased interaction of Adamts1 with its endogenous inhibitor TIMP3. The AMPK inhibitor compound C blocked the EtOH-induced stimulation of collagen and O-GLcNAc Adamts1 protein. Changes in AMPK appear linked to FoxO1, since inhibition of FoxO1 blocked the effects of EtOH on AMPK phosphorylation and O-GLcNAc levels. These FoxO-dependent modifications were associated with an upregulation of the FoxO1 transcription target sestrin 3, as well as increased binding of sestrin 3 with AMPK. Collectively, these data indicate that EtOH regulates the collagen I and elastin content in an Adamts1-dependent manner in myocytes. Furthermore, Adamts1 appears to be controlled by the FoxO1-sestrin 3-AMPK signaling cascade.

In this paper, the ZTC4/B/C titanium matrix composite containing 0·2–0·5 wt-%B and 0·5–2 wt-%C was fabricated using melting–casting process. The microstructure and mechanical properties of as cast ZTC4/B/C Ti matrix composite were investigated. The results indicate that the microstructures of as cast ZTC4/B/C were consisted of lamellar α, β at grain boundary and second phases of bar-like TiB and spherical-like TiC. The elastic modulus of ZTC4/B with 0·5 wt-%B is 145 GPa, 30% higher than that of the matrix alloy. The ultimate tensile strength of ZTC4/B/C with 0·5 wt-%B and 0·5 wt-%C reached 1300 MPa, 25% higher than that of the matrix alloy.

Tensile tests were carried out at ambient temperature on one kind of near α titanium alloy named Ti-600 before and after being exposed at 600°C for 100 h. Fractography morphologies were investigated and fracture mechanisms were analysed. The results indicate that, compared with the sample without thermal exposure, the strength of the sample without oxidising layers increases by 1% or so, while the elongation decreases by about 20·4% for the alloy after thermal exposure. For the sample with oxidising layers, the ultimate strength decreases somewhat and the elongation decreases by 48·9%, indicating that the plasticity decreases abruptly during the thermal exposure process. For the solutioned plus aged samples, cracks originated from the centre of the fracture, and dimple-type fractures could be found. After long thermal exposure, for the samples without oxidising layers, hybrid fractures (both dimples and cleavage facets) can be seen. However, for the samples with oxidising layers, only cleavage fac...

ObjectiveLimited studies have shown an association between the methyl-CpG-binding protein2 ( MeCp2) genetic polymorphisms and systemic lupus erythematosus (SLE) in different populations, but the results are inconclusive. In order to get a precise and systematic estimation, a meta-analysis was performed.MethodsA systematic literature search using English and Chinese databases (PubMed/Medline, Web of Knowledge, Wanfang Data (Chinese), etc.) for the eligible studies was performed. Based on heterogeneity among studies, random- or fixed-effects models were selected to analyze the risk of SLE associated with single-nucleotide polymorphisms (SNPs) of MeCP2 genetic polymorphisms.ResultsA significant increased risk of both SNPs of MeCP2 genetic variances associated with SLE was found. Analysis using a fixed-effects model found an increased risk of SLE with the A allele of rs2075596 (OR = 1.41, 95% CI: 1.34 to 1.49, p ConclusionsMutations of SNPs ( rs2075596, rs2239464) of MeCP2 showed increased risk of developing SLE. Large-scale multicenter epidemiological studies in selected populations with other risk factors are urgently required.

Nuclear receptor coactivator amplified in breast cancer-1 (AIB1), a new oncogenic coactivator, is commonly overexpressed and amplified in variety of human cancers. However, the expression of AIB1 in papillary thyroid carcinoma (PTC), the major histologic type of thyroid cancer, and its clinical significance are still unclear.AIB1 expression in PTC was examined by immunohistochemistry using tissue microarrays comprised of 90 primary PTC, 46 matched lymph node, and 20 normal thyroid tissue specimens in this study.In the normal thyroid specimens, AIB1 expression was either absent or at low levels. In contrast, AIB1 overexpression was detected in 50 of 83 (60.2 %) primary PTC specimens. Up-regulated AIB1 was evident in 39 of 46 (73.5 %) matched lymph nodes. Overexpression of AIB1 was observed more frequently in PTCs with lymph node metastasis [N1a/N1b, 39/46 (73.5 %)] versus PTCs without lymph node metastasis [N0, 14/34 (41.2 %)]. Furthermore, high-level AIB1 expression was only observed in the lymph node-positive specimens. Moreover, we found no correlation between AIB1 expression and ER expression in PTC tissues.Our findings suggest that overexpression of AIB1 may be a biomarker for tumorigenesis and progression of PTC and may play an important role in its acquisition of a metastatic phenotype.

Background Excessive alcohol (EtOH) consumption causes an imbalance in protein metabolism. EtOH impairs protein synthesis in C2C12 myoblasts via a FoxO1-AMPK-TSC2-mTORC1 pathway and also induces protein degradation. As the underlying regulatory signaling cascades for these processes are currently poorly defined, we tested the hypothesis that alcohol-induced autophagy is mediated via activation of the PIK3C3 complex that is regulated by FoxO1-AMPK. Methods C2C12 myoblasts were incubated with EtOH for various periods of time, and autophagy pathway-related proteins were assessed by Western blotting and immunoprecipitation. Expression of targeted genes was suppressed using electroporation of specific siRNAs and chemical inhibitors. Results Incubation of C2C12 myoblasts with 100 mM EtOH increased the autophagy markers LC3B-II and ATG7, whereas levels of SQSTM1/p62 decreased. The lysosomal inhibitor bafilomycin A1 caused a similar response, although there was no additive effect when combined with EtOH. EtOH altered ULK1 S555 and S757 phosphorylation in a time- and AMPK-dependent manner. The activation of AMPK and ULK1 was associated with increased BECN1 (S93, S14) and PIK3C3/VPS34 (S164) phosphorylation as well as increased total ATG14 and PIK3C3. These changes promoted formation of the ATG14-AMBRA1-BECN1-PIK3C3 proautophagy complex that is important in autophagosome formation. EtOH-induced changes were not associated with increased production of PtdIns3P, which may be due to enhanced PIK3C3 complex binding with 14-3-3θ. Reduction of AMPK using siRNA suppressed the stimulatory effect of EtOH on BECN1 S93, BECN1 S14, and PIK3C3 S164 phosphorylation in a time-dependent manner. Likewise, knockdown of AMPK or chemical inhibition of FoxO1 attenuated phosphorylation of ULK1 at both residues. Knockdown of ULK1 or BECN1 antagonized the effect of EtOH on LC3B-II, SQSTM1, and ATG7 protein expression. Conclusions EtOH-induced autophagy is mediated through changes in phosphorylation and interaction of various PIK3C3 complex components. This, in turn, is regulated either directly via FoxO1-AMPK or indirectly via the FoxO1-AMPK-ULK1 signaling cascade in a mTORC1-independent or mTORC1-dependent manner.

To study the characteristics and prevention and treatment strategies of massive hemorrhage caused by fungal infections after donation-after-cardiac-death (DCD) kidney transplantation.A total of 91 cases of DCD kidney transplantation between August 25, 2013 and June 30, 2015 in Third Affiliated Hospital of Sun Yat-sen Univservity were retrospectively analyzed. The characteristics of and prevention and treatments strategies for postoperative massive hemorrhage caused by fungal infections were summarized.Ninety-one cases of DCD kidney transplantation were divided into 2 groups based on regimens for preventing postoperative fungal infections: fluconazole prophylaxis group: a total of 26 cases of renal transplant before June 11, 2014 received fluconazole regimen, from postoperative day 0 to 2 weeks; micafungin prophylaxis group: a total of 65 cases of renal transplant after June 11, 2014 received micafungin regimen, also for 2 weeks from postoperative day 0. Two cases in fluconazole group developed postoperative massive hemorrhage. In case 1, the hemorrhage occurred at 2 weeks after transplantation. Graft nephrectomy was performed during surgical exploration for hemostasis, yet the massive hemorrhage relapsed 2 weeks later. Endoluminal exclusion of external iliac artery using endovascular covered stent-graft at the anastomosis site was performed and the massive bleeding was successfully stopped. The patient was restored to hemodialysis and waited for second kidney transplantation. Candia albicans was detected in the culture of blood and drainage liquid from incision. The other case of hemorrhage occurred at 3 weeks after transplantation. Graft nephrectomy plus endovascular exclusion using covered stent-graft were also performed to stop the massive bleeding. Massive fungal hyphae and spores were observed at the stump of renal graft artery under microscope. The patient received second kidney transplantation after 6 months successfully. No massive hemorrhage caused by fungal infections occurred in micafungin prophylaxis group.Massive hemorrhage cased by fungal infections after DCD kidney transplantation is usually characterized by delayed and recurrent course, and may result in graft nephrectomy or even death of patients. Endovascular exclusion using covered stent can successfully stop bleeding and rescue life of patients. Two-week preemptive prophylaxis of fungal infections using micafungin can effectively prevent delayed fungal massive hemorrhage in DCD kidney transplantation.

The singularity expansion method (SEM) assumes that the electromagnetic scattering wave of an object has a fixed poles distribution, i.e. the resonant frequency is fixed. So the object can be identified by extracting poles from radar data. While studying ground penetrating radar (GPR) echo signal features of nonmetallic pipelines, the paper finds that the GPR signal's frequency center downshifts when a nonmetallic pipeline is placed in an underground half space, when compared with it being placed in free space. The FDTD calculation model for a nonmetallic pipeline placed in different spaces is established. Through model calculation, the result shows the same phenomenon as the test data. More calculations indicate that the phenomenon of GPR echo frequency center shift has little relationship with the depth of the nonmetallic pipeline underground, but relates closely to the relative permittivity of the nonmetallic pipeline and the surrounding medium. Furthermore, from the phase change when electromagnetic waves pass through the interface of different media, we elaborate the physical mechanism of frequency shift and find the characteristics of the GPR signal of nonmetallic pipelines in different spaces. It has practical significance for the GPR detection of nonmetallic pipelines.

This study aimed to construct breast cancer image screening consultation network (BISCN) that connects all levels of medical institutions in Guangdong Province.Fourteen hospitals in different cities and counties (districts) of Guang-dong were selected for breast cancer screening with imaging (breast X-ray, ultrasound, and MRI). "Breast Imaging Reporting and Data System (BI-RADS)" was taken as reference to build up image data base of breast cancer screening and BISCN that is an internet-based network platform. BISCN quality control was performed to improve the diagnostic accuracy and collaboration of members. In 2011, the BISCN members underwent breast imaging diagnosis training and conducted a questionnaire survey.BISCN allowed quick, synchronous, and accurate communication and feedback of diagnostic imaging in breast cancer among all levels of medical institutions and improved the ability of breast cancer screening in the province, as well as the detection rate of early breast cancer throughout the province, especially in the grassroot units. The survey results showed that the trainees' understanding situation of the training contents before training was 2.02 ± 1.75 points. Through the study, the participants considered that the teaching contents could solve the daily diagnose problems (2.91 ± 0.70 points), the post-training scores were improved (2.88 ± 1.23 points), and highly satisfactory with the teaching contents (2.81 ± 0.53 points). All students passed the examination and were qualified for the future.BISCN is of good feasibility in construction and applicability in management by raising diagnosis level of breast cancer in Guangdong Province.

The FPV140 gene encodes an envelope protein of fowlpox virus (FPV). In this study, the FPV140 gene of FPV Chinese isolate HH2008 was cloned and the comparison of its sequence with other FPV isolates showed it to be highly conserved across all FPV isolates. A recombinant plasmid pET-FPV140 carrying FPV140 gene was constructed and transformed into Escherichia coli. The optimal expression condition for the FPV140 gene was developed and purified FPV140 recombinant protein was used to produce rabbit polyclonal antibody. An indirect ELISA using this anti-FPV140 polyclonal antibody was capable of distinguishing avian FPV isolates from other common avian pathogens such as mycoplasma gallisepticum, infectious laryngotracheitis virus, avian influenza virus, infectious bursal disease virus, and avian infectious bronchitis virus. This ELISA will serve as a useful diagnostic tool for the detection of FPV in clinical samples.

Leucine (Leu) and insulin both stimulate muscle protein synthesis, albeit at least in part via separate signaling pathways. While alcohol (EtOH) suppresses insulin-stimulated protein synthesis in cultured myocytes, its ability to disrupt Leu signaling and Rag GTPase activity has not been determined. Likewise, little is known regarding the interaction of EtOH and Leu on the AMPK/TSC2/Rheb pathway. Treatment of myocytes with EtOH (100 mM) decreased protein synthesis, whereas Leu (2 mM) increased synthesis. In combination, EtOH suppressed the anabolic effect of Leu. The effects of EtOH and Leu were associated with coordinate changes in the phosphorylation state of mTOR, raptor, and their downstream targets 4EBP1 and S6K1. As such, EtOH suppressed the ability of Leu to activate these signaling components. The Rag signaling pathway was activated by Leu but suppressed by EtOH, as evidenced by changes in the interaction of Rag proteins with mTOR and raptor. Overexpression of constitutively active (ca)RagA and caRagC increased mTORC1 activity, as determined by increased S6K1 phosphorylation. Furthermore, the caRagA-caRagC heterodimer blocked the inhibitory effect of EtOH. EtOH and Leu produced differential effects on AMPK signaling. EtOH enhanced AMPK activity, resulting in increased TSC2 (S1387) and eEF2 phosphorylation, whereas Leu had the opposite effect. EtOH also decreased the interaction of Rheb with mTOR, and this was prevented by Leu. Collectively, our results indicate that EtOH inhibits the anabolic effects that Leu has on protein synthesis and mTORC1 activity by modulating both Rag GTPase function and AMPK/TSC2/Rheb signaling.

Ternary monomer graft copolymers (PPTM) were synthesised by solid phase grafting maleic anhydride (MAH), methyl methacrylate (MMA) and butyl acrylate (BA) onto polypropylene (PP) and used as compatibilisers for rice chaff (RC) filled recycled polypropylene (rPP) composites. How the graft copolymers affected the mechanical properties, water absorption, morphology, crystallisation and melting behaviour and thermal stability of rPP/RC composites was investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermal-gravity analysis (TGA), etc. Results showed that the graft copolymers can dramatically improve the interface adhesion of rPP/RC composites. The strong interface adhesion of the composites primarily came from the formation of the ester bonds between the hydroxyl groups of cellulosic fibres and the anhydride carbonyl groups of PPTM, and the hydrogen bonding between the hydroxyl groups of cellulosic fibres and the carbonyl groups of PPTM. The mechanical pr...

The mechanism by which human immunodeficiency virus (HIV)-1 infection in humans leads to the erosion of lean body mass is poorly defined. Therefore, the purpose of the present study was to determine whether transgenic (Tg) rats that constitutively overexpress HIV-1 viral proteins exhibit muscle wasting and to elucidate putative mechanisms. Over 7 mo, Tg rats gained less body weight than pair-fed controls exclusively as a result of a proportional reduction in lean, not fat, mass. Fast- and slow-twitch muscle atrophy in Tg rats did not result from a reduction in the in vivo-determined rate of protein synthesis. In contrast, urinary excretion of 3-methylhistidine, as well as the content of atrogin-1 and the 14-kDa actin fragment, was elevated in gastrocnemius of Tg rats, suggesting increased muscle proteolysis. Similarly, Tg rats had reduced cardiac mass, which was independent of a change in protein synthesis. This decreased cardiac mass was associated with a reduction in stroke volume, but cardiac output was maintained by a compensatory increase in heart rate. The HIV-induced muscle atrophy was associated with increased whole body energy expenditure, which was not due to an elevated body temperature or secondary bacterial infection. Furthermore, the atrophic response could not be attributed to the development of insulin resistance, decreased levels of circulating amino acids, or increased tissue cytokines. However, skeletal muscle and, to a lesser extent, circulating insulin-like growth factor I was reduced in Tg rats. Although hepatic injury was implicated by increased plasma levels of aspartate and alanine aminotransferases, hepatic protein synthesis was not different between control and Tg rats. Hence, HIV-1 Tg rats develop atrophy of cardiac and skeletal muscle, the latter of which results primarily from an increased protein degradation and may be related to the marked reduction in muscle insulin-like growth factor I.

Ethanol decreases protein synthesis in cells, although the underlying regulatory mechanisms of this process are not fully established. In the present study incubation of C2C12 myocytes with 100 mm EtOH decreased protein synthesis while markedly increasing the phosphorylation of eukaryotic elongation factor 2 (eEF2), a key component of the translation machinery. Both mTOR and MEK pathways were found to play a role in regulating the effect of EtOH on eEF2 phosphorylation. Rapamycin, an inhibitor of mammalian target of rapamycin, and the MEK inhibitor PD98059 blocked the EtOH-induced phosphorylation of eEF2, whereas the p38 MAPK inhibitor SB202190 had no effect. Unexpectedly, EtOH decreased the phosphorylation and activity of the eEF2 upstream regulator eEF2 kinase. Likewise, treatment of cells with the inhibitor rottlerin did not block the stimulatory effect of EtOH on eEF2, suggesting that eEF2 kinase (eEF2K) does not play a role in regulating eEF2. In contrast, increased eEF2 phosphorylation was correlated with an increase in AMP-activated protein kinase (AMPK) phosphorylation and activity. Compound C, an inhibitor of AMPK, suppressed the effects of EtOH on eEF2 phosphorylation but had no effect on eEF2K, indicating that AMPK regulates eEF2 independent of eEF2K. Finally, EtOH decreased protein phosphatase 2A activity when either eEF2 or AMPK was used as the substrate. Thus, this later action may partially account for the increased phosphorylation of eEF2 in response to EtOH and the observed sensitivity of AMPK to rapamycin and PD98059 treatments. Collectively, the induction of eEF2 phosphorylation by EtOH is controlled by an increase in AMPK and a decrease in protein phosphatase 2A activity.

Esophageal cancer-related gene 4 (ECRG4) is a new candidate tumor suppressor gene. In this retrospective study, we evaluated ECRG4 protein expression in patients with nasopharyngeal carcinoma (NPC) under curative treatment and examined its association with pathological features and clinical outcomes as a possible biomarker for diagnosis and prognosis of NPC. We enrolled 122 patients with a first diagnosis between January 2001 and December 2003. Tumor tissue and control tissue from biopsies underwent immunohistochemical staining for ECRG4. ECRG4 expression was analyzed by clinicopathological variables. After Kaplan–Meier survival analysis, we used Cox proportional hazards regression to estimate the predictive effect of ECRG4 expression on overall survival. ECRG4 protein level was lower in NPC than control tissue (P