[Expert consensus on graded management of antineoplastic drugs].

The standardized diagnosis and treatment of tumor and the rational use of antineoplastic drugs are not only the central issue of the government and society, but also the difficulty of medical quality control. In order to implement "the Administrative Measures for the Clinical Application of Antineoplastic Drugs (Trial)" issued by the National Health Commission of the People's Republic of China, on the basis of extensive investigation and through Delphi method and several rounds of expert discussion, an expert consensus on the guiding road map and management points of drug classification was formed. Suggestions are provided to guide other medical institutions to do the related work in the graded management of antineoplastic drugs.

[Cathepsin L mediates glomerular endothelial cell injury by cleavaging complement C3 in trichloroethylene-sensitized mice].

Objective: To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice. Methods: In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group (n=5) , vehicle control group (n=5) , TCE group (n=15) and TCE+CTSLi group (n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results: The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups (P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group (P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group (P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group (P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group (P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant (P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group (P<0.05) . Conclusion: CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

[Effect of complement C5a on the expression of MCP-1 and NGAL in immune kidney injury of trichloroethylene sensitized mice].

Objective: To explore the possible role of C5a in the pathogenesis of renal injury in TCE- sensitized mice, to analyze the impact of expression of neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemotactic protein-1 (MCP-1) in the presence or absence of C5a receptor antagonist (C5aRA) pretreatment. Methods: A total of 50 female specific pathogens free(SPF) BALB/c mice were randomly divided into blank control group (n=5) , solvent control group (n=5) , TCE group (n=20) , and TCE+C5aRA group (n= 20) . After one week for adaptive feeding, a mouse model of TCE-induced skin sensitization was established by treating with 50% TCE and 30% TCE in turn. The mice in solvent control group accept same reagents without TCE and the mice in blank control group underwent nothing. In TCE +C5aRA group, except for the TCE solution treatment, mice were intraperitoneally injected with 0.5 mg/kg C5aRA solution at the time of challenge. And the skin erythema and edema reaction were scored 24 h after the last challenge. The mice were divided into sensitization positive group and sensitization negative group according to the scoring result. The mice were aseptically sacrificed 72 h after the last challenge to obtain the kidneys. The structural damage of kidney was observed after histopathological staining. The levels of NGAL and MCP-1 mRNA and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) , respectively. Results: The sensitization rate of mice in TCE group and TCE+C5aRA group was 45.0% (9/20) and 40.0% (8/20) , respectively. No skin lesions was found in the mice of blank control group and solvent control group. The results of histopathological staining showed that the TCE sensitization positive mice showed renal tubular dilatation, vacuolar degeneration of renal tubular epithelial cells, and infiltration of interstitial cells. The pathological damage of the kidney in TCE sensitization positive group was mild, and no inflammatory cell infiltration was seen. The data of qRT-PCR showed that the expression levels of NGAL and MCP-1 mRNA in the TCE sensitization positive group were significantly increased than in solvent control group and TCE sensitization negative group (P<0.05) , while the levels of NGAL and MCP-1 mRNA in TCE+C5aRA sensitization positive group were decreased than TCE sensitization positive group (P <0.05) . The results of IHC showed that the expression levels of NGAL and MCP-1 in TCE protein sensitization positive group were significantly higher than those in solvent control group and TCE sensitization negative group (P<0.05) . After C5aRA pretreatment, the expression levels of NGAL and MCP-1 protein were decreased than the mice in TCE sensitization positive group (P<0.05) . Conclusion: The regulation of C5a on the expression of MCP-1 and NGAL may participate in TCE- induced mice kidney damage, and pharmacological inhibition of C5a seems to be an effective way to protect the kidney injury in TCE-sensitized mice.

[Association between D-dimer levels and clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy].

Objective: To investigate the association between D-dimer levels and clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy. Methods: This prospective study included 640 consecutive patients underwent mechanical heart valve replacement in Wuhan Asia Heart Hospital between January 2013 and June 2014.Patients were assigned to abnormal D-dimer group (D-dimer level>cut off value, n=88) and normal D-dimer group (D-dimer level≤cut off value, n=552) according to D-dimer levels measured at 3 months after the initiation of oral anticoagulation therapy.All patients were followed up for 24 months or until the observation of the end points, which included thrombotic events, bleeding events and all-cause deaths.The anticoagulation therapy was monitored once per 1-2 months by the international normalized ratio (INR), and the target value was 1.8-3.0. Results: During a follow-up period of 24 months, rates of total clinical events (19.30%(17/88) vs. 5.8%(32/552), P<0.01), thrombotic events (11.4%(10/88) vs. 2.3%(13/552), P<0.01), and all-cause deaths (8.0%(7/88) vs. 2.0%(11/552), P<0.01) were all significantly higher in abnormal D-dimer group than in normal D-dimer group.There were no significant difference in bleeding events between the two groups (2.3%(2/88) vs. 3.1%(17/552), P=0.77). Multivariate Cox regression analysis showed that high D-dimer level was an independent risk factor of total clinical events (HR=3.86, 95%CI 1.92-7.76, P<0.01), thrombotic events(HR=5.29, 95%CI 2.12-13.10, P<0.01), and all-cause deaths(HR=5.32, 95%CI 1.71-16.60, P<0.01), but which was not correlated with bleeding events(HR=1.36, 95%CI 0.27-6.84, P=0.71). Conclusion: Elevated D-dimer levels are linked with clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy.

Symmetry breaking induced excitations of dark plasmonic modes in multilayer graphene ribbons.

Multilayer graphene can support multiple plasmon bands. If structured into graphene ribbons, they can support multiple localized plasmonic modes with interesting optical properties. However, not all such plasmonic modes can be excited directly due to the constrains of the structural symmetry. We show by numerical simulations that by breaking the symmetry all plasmonic modes can be excited. We discuss the general principles and properties of two-layer graphene ribbons and then extend to multilayer graphene ribbons. In multilayer graphene ribbons with different ribbon widths, a tunable broadband absorption can be attained due to the excitations of all plasmonic modes. Our results suggest that these symmetry-broken multilayer graphene ribbons could offer more degrees of freedom in designing photonic devices.

CoxNi100-x nanoparticles encapsulated by curved graphite layers: controlled in situ metal-catalytic preparation and broadband microwave absorption.

We report a one-step approach for preparing dispersive CoxNi100-x nanoparticles completely encapsulated by curved graphite layers. The nanoparticles were prepared by evaporating Co-Ni alloys and the shell of graphite layers was formed by in situ metal-catalytic growth on the surface of nanoparticles whose layer number was controlled by tuning the Co content of the alloys. By modulating the composition of the magnetic core and the layer number of the shell, the magnetic and dielectric properties of these core/shell structures are simultaneously optimized and their permeability and permittivity were improved to obtain the enhanced electromagnetic match. As a result, the bandwidth of reflection loss (RL) exceeding -20 dB (99% absorption) of the nanocapsules is 9.6 GHz for S1, 12.8 GHz for S2, 13.5 GHz for S3 and 14.2 GHz for S4. The optimal RL value reaches -53 dB at 13.2 GHz for an absorber thickness of 2.55 mm. An optimized impedance match by controlling the growth of the core and shell is responsible for this extraordinary microwave absorption.

Vascular endothelial growth factor increases GEnC permeability by affecting the distributions of occludin, ZO-1 and tight juction assembly.

OBJECTIVE: To explore the molecular mechanism of the increased permeability of glomerular endothelial cells (GEnC) stimulated by vascular endothelial growth factor (VEGF). METHODS: We investigated the permeability-increasing effect and tight junction formation of VEGF by measuring FITC labeled BSA across GEnC monolayer. Then, immunofluorescence and western blot were employed to detect the distributions of occludin and ZO-1. RESULTS: We found that VEGF increased FITC-BSA permeability. VEGF also caused a loss of occludin and ZO-1 from the endothelial cell junctions, and changed the staining pattern of the cell boundary. Western blot analysis of GEnC lysates revealed that occludin and ZO-1 were redistributed under VEGF treatment. CONCLUSIONS: These results suggested that VEGF could increase GEnC monolayer permeability by changing distributions and organizations of occludin and ZO-1, which lead to tight junction disassembly. Occludin and ZO-1 appeared to be downstream effectors of the VEGF signaling pathway.

Correlated increase of omentin-1 and adiponectin by exenatide, avandamet and dietary change in diet-induced obese rats.

Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorate metabolic disorders. However, whether these treatments increase omentin-1 levels in high fat-diet animals and the relationship between omentin- 1 and adiponectin remain largely unknown. We investigated the effect of insulin sensitizers exenatide and avandamet, and of dietary change on these adipokine levels, body weight, and insulin sensitivity in diet-induced obese rats. Obesity was induced in rats by high-fat diet feeding for 8 weeks, and then the rats were given exenatide, avandamet and diet change to normal chow, respectively, for additional 8 weeks. Compared to the high-fat control group, exenatide and avandamet treatment significantly induced adipose gene expression and elevated the circulation levels of omentin-1 and adiponectin, whereas they decreased the leptin gene expression and circulation level, which is associated with improvement of systemic insulin sensitivity and the glucose and lipid profile. Notably, there was a significant positive correlation between omentin-1 and adiponectin in the above regimens, suggesting that omentin-1 and adiponectin may contribute to the insulin-sensitizing effect of exenatide and avandamet.

Be alert to the alterations in the biological characteristics in heterogeneous vancomycin-intermediate Staphylococcus aureus.

The development of reduced vancomycin susceptibility in Staphylococcus aureus in many cases appears to be associated with characteristic changes. These changes may have pitfall of identifying S. aureus by automated testing methods like Vitek 32. In this study, we retested 24 heterogeneous vancomycin-intermediate Staphylococcus haemolyticus (h-VISH) collected in 2008-2010 at the Department of Clinical Microbiology by conventional biochemical tests and polymerase chain reaction (PCR). The heterogeneous vancomycin-intermediate S. aureus (hVISA) reversion test and electron microscopic examination were also used. Six isolates of 24 h-VISH possessed nuc, coa, and 16S rRNA genes, and could be reversed into S. aureus. It suggested that biochemical and morphological changes in hVISA and vancomycin-intermediate S. aureus (VISA) should be considered, and the detection of S. aureus, especially reduced vancomycin susceptibility isolates, requires more attention and different techniques.

Treatment of oesophageal anastomotic leaks by temporary stenting with self-expanding plastic stents.

BACKGROUND: Oesophageal anastomotic leakage is associated with considerable morbidity and mortality. The aim of the present study was to assess the feasibility of using temporary self-expanding plastic stents to treat postoperative oesophageal leaks. METHODS: Patients with anastomotic leakage after abdominothoracic oesophagectomy treated by endoscopic insertion of self-expanding plastic stents between 2001 and 2007 were studied. Clinical outcomes were analysed, including healing of the leak, morbidity and mortality. RESULTS: Stents were inserted successfully in all 22 patients without procedure-related complications. Ten patients also required computed tomography-guided drainage because surgical drains had been removed. Non-ventilated patients received oral nutrition a mean of 4 days after stent placement. Combined treatment with stenting and drainage resulted in resolution of the leak in 21 of 22 patients. The mean healing time (time to stent removal) was 23 days. Stent migration occurred in five of 22 patients, but endoscopic reintervention with placement of a new stent was successful in all patients. Repeat thoracotomy with intraoperative stent placement was necessary in one patient with an oesophagocolonic anastomosis. One patient died in hospital. CONCLUSION: In combination with effective drainage, self-expanding plastic stents are an option for the treatment of oesophageal anastomotic leaks, and may reduce leak-related morbidity and mortality.

Synthesis of micrometer-sized hard silica spheres with uniform mesopore size and textural pores.

Micrometer-sized silica spheres were prepared using a new pH-induced rapid colloid aggregation method in water-in-oil (W/O) emulsion separately with F127 and the mixture of Pluronic triblock copolymer (F127, P123, or P105) and PEG20000 as templates. All the mesoporous silica spheres exhibited high surface areas (657-1145 m2/g) and large pore volumes (0.46-2.16 ml/g). Through optimizing the synthetic conditions, hard silica spheres with narrow particle size distribution, uniform pore size, and textural pores were obtained. Finally, the mechanism of this synthetic route is discussed.