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Biomedical subjects

Xiaoyun Liu

Publications and source records attributed to Xiaoyun Liu.

15 recordsLinked to original sources

Multiple perspectives on diagnosis delay for tuberculosis from key stakeholders in poor rural China: case study in four provinces.

This study aims to understand the contextual barriers to accessing timely TB diagnosis after first seeking care, especially among the poor and vulnerable in rural China. Both quantitative and qualitative methods were used to elicit the experiences and perspectives of TB patients and suspected TB patients, community residents, health providers and policy makers in poor, rural areas of four provinces. Between 30 and 60% of patients across the four provinces experienced a delay in receiving a diagnosis after first seeking care. Most patients had to visit health facilities more than once before diagnosis, with 17-30% patients making more than 6 visits. These delays and multiple visits mainly occurred because of the limited capacity of health providers to recognize TB, and financial disincentives to refer patients to TB dispensaries, due to the pressures of the cost recovery system. Poverty and socio-economic disadvantage amongst patients also influenced their capability to seek further care to obtain a reliable diagnosis. Qualitative data showed that women and the elderly patients were likely to experience more 'system' delay, and these findings were to some extent supported by the survey. The study concludes that 'system' delay is a serious problem, which is influenced by the financing mechanisms for both TB control and general health services as well as poverty and disadvantage amongst patients. This requires a comprehensive strategy to shorten 'system' delay in order to enable successful DOTS expansion, including developing appropriate financing mechanisms to improve general provider capacity and encourage referral, as well as measures to improve financial and social access to services for potential TB patients.

Adolescent↗

Does decentralisation improve human resource management in the health sector? A case study from China.

A major obstacle to the provision of health services is lack of an effective workforce. Human resource management (HRM) can improve the effectiveness of the workforce, though this is difficult in large bureaucratic organisations. Decentralisation is a common reform strategy and this paper sets out to examine whether HRM would be improved in decentralised settings. Indicators were developed for three areas of HR outcome: (i) appropriate staff numbers, with (ii) appropriate skills and experience, providing, (iii) appropriate inputs to organisational performance. An attempt was made to link these human resource (HR) outcomes to relevant HRM actions in two counties--one richer and one poorer--in Fujian Province, China. One general county hospital and 5 township health centres were selected for study in each country. A health facility-based survey collected information on characteristics of the workforce and staff surveys identified changes in the management of human resources and staff inputs to performance before and after decentralisation. Whilst some benefits were identified from decentralising HRM, the complexity of the decentralisation itself, and other external pressures coupled with inadequate capacity building meant that some HRM actions were not always aligned with health service objectives. Better planning and preparation coupled with strong monitoring would increase the chances of decentralisation improving HRM in the health sector.

China↗

Perceptions of tuberculosis and health seeking behaviour in rural Inner Mongolia, China.

PURPOSE: This study aimed to explore perceptions of TB, and health care seeking pathways, among poor rural communities in Inner Mongolia. METHODOLOGY: Twenty focus group discussions (FGDs) were held and 105 farmers were included. Six hundred and fourteen randomly selected respondents were surveyed through interview questionnaire, in three poor rural counties with a high TB prevalence. MAIN FINDINGS: A substantial proportion of community members were unclear or misinformed as to how TB was transmitted. Sixty percent of respondents identified prolonged cough as a main symptom of TB, while only 40% perceived TB to be caused by 'close interaction with TB patient'. In addition, 70% could not afford TB treatment and fell into debt as a result of having to seek medical care. Social stigma associated with TB influenced marriage prospects and impeded important social interactions within the community. Respondents' perceptions of TB were associated with their socio-economic status. Women, young people, low-income groups and those with less education tended to be less knowledgeable about TB. All farmers in the study reported only seeking health care after they failed to treat themselves; and most of them then sought care from less qualified village level health care providers. Less educated people, low-income groups and old people were identified as less likely to seek care, or more likely to seek care at village level where it is cheaper. Both financial and structural barriers were found to stop farmers seeking health care. CONCLUSIONS AND POLICY IMPLICATIONS: Perceptions of TB and social stigma associated with the disease, together with socio-economic factors, shape the health seeking behaviour of poor farmers. Accessibility and affordability of TB health care issues should be dealt with through a multi-pronged approach, including health promotion in addition to expansion of the DOTS strategy and rural health insurance schemes.

Adolescent↗

Efficient and stable gene expression in rabbit intervertebral disc cells transduced with a recombinant baculovirus vector.

STUDY DESIGN: A recombinant baculovirus vector expressing GFP (Ac-CMV-GFP) was tested in rabbit intervertebral disc cells cultured in monolayer in vitro. Direct infection of intervertebral disc cells was then assessed in vivo. OBJECTIVES: To test the efficacy of the baculovirus-mediated marked gene transfer to rabbit intervertebral disc cells, and the expression of the transgene in vitro and in vivo. SUMMARY OF BACKGROUND DATA: The potential application of gene therapy for the treatment of degenerative disc disease has been an area of exciting and active research. Many efforts have been made toward the construction of delivery vectors using mammalian viruses, such as adenovirus, adeno-associated virus, retrovirus, and herpesvirus. However, recently, baculovirus-derived vectors have emerged as possible tools for gene transfer into mammalian cells in vitro and in vivo but, to our knowledge, have never been tested in an intervertebral disc cell. METHODS: The intervertebral disc cells cultured in monolayer were treated with 6 different doses of baculovirus carrying the green fluorescence protein gene (Ac-CMV-GFP). Fluorescence microscopy and flow cytometry were used to analyze transgene expression. The Autographa californica nucleopolyhedrovirus/GFP virus was then injected directly into the intervertebral discs of 8 rabbits at 7, 13, 20, and 28 days after injection. The nucleus pulposus tissues of injected discs were evaluated immediately by fluorescence microscopy for GFP expression. RESULTS: A dose of Ac-CMV-GFP at a multiplicity of infection of 200 achieved the highest transduction ratio (approximately 87% of nucleus pulposus cells) and long-term expression without any toxicity to the cells. In vivo assay showed that Ac-CMV-GFP could also mediate GFP expression in rabbit intervertebral disc cells without inducing any symptoms. The GFP expression level at 7 days after transduction was significantly higher than at 21 and 28 days after treatment. CONCLUSIONS: Baculovirus can transfer exogenous genes into rabbit nucleus pulposus cells at a high efficiency, and safely both in vitro and in vivo. The results suggest that baculoviruses might be useful tools as gene therapy vectors for intervertebral disc diseases.

Animals↗

Toward plasma proteome profiling with ion mobility-mass spectrometry.

Differential, functional, and mapping proteomic analyses of complex biological mixtures suffer from a lack of component resolution. Here we describe the application of ion mobility-mass spectrometry (IMS-MS) to this problem. With this approach, components that are separated by liquid chromatography are dispersed based on differences in their mobilities through a buffer gas prior to being analyzed by MS. The inclusion of the gas-phase dispersion provides more than an order of magnitude enhancement in component resolution at no cost to data acquisition time. Additionally, the mobility separation often removes high-abundance species from spectral regions containing low-abundance species, effectively increasing measurement sensitivity and dynamic range. Finally, collision-induced dissociation of all ions can be recorded in a single experimental sequence while conventional MS methods sequentially select precursors. The approach is demonstrated in a single, rapid (3.3 h) analysis of a plasma digest sample where abundant proteins have not been removed. Protein database searches have yielded 731 high confidence peptide assignments corresponding to 438 unique proteins. Results have been compiled into an initial analytical map to be used -after further augmentation and refinement- for comparative plasma profiling studies.

Blood Proteins↗

[Studies on the preparation and characterization of immobilized neutral protease by carboxymethyl chitosan microsphere].

AS1. 398 neutral protease was immobilized onto carboxymethyl chitosan with glutaraldehyde as cross-linking agent. The effects of pH, time of cross-linking, amount of cross-linking agent and the ratio of enzyme to carrier on the activity of the immobilized enzyme were demonstrated, and the optimum immobilization condition of AS1. 398 neutral protease was established. Also studied was the characterization of immobilized enzyme,including pH, temperature, Km and the stability of storage.

Bacterial Proteins↗

The generation of immunotoxins using chimeric anti-CD22 antibodies containing mutations which alter their serum half-life.

Murine and chimeric RFB4 (anti-human CD22) monoclonal antibodies (MAbs) with mutations in their Fc portions were conjugated to recombinant ricin toxin A chain to generate immunotoxins. The resulting immunotoxins (ITs) constructed with chimeric RFB4 MAbs were designed to have longer or shorter half-lives but similar binding and cytotoxic properties. These ITs can now be evaluated in vivo for improved therapeutic indices. The characteristics of these ITs are the subject of this report.

Animals↗

Developing liquid chromatography ion mobility mass spectometry techniques.

When a packet of ions in a buffer gas is exposed to a weak electric field, the ions will separate according to differences in their mobilities through the gas. This separation forms the basis of the analytical method known as ion mobility spectroscopy and is highly efficient, in that it can be carried out in a very short time frame (micro- to milliseconds). Recently, efforts have been made to couple the approach with liquid-phase separations and mass spectrometry in order to create a high-throughput and high-coverage approach for analyzing complex mixtures. This article reviews recent work to develop this approach for proteomics analyses. The instrumentation is described briefly. Several multidimensional data sets obtained upon analyzing complex mixtures are shown in order to illustrate the approach as well as provide a view of the limitations and required future work.

Animals↗

Beam shaping of focused partially coherent beams by use of the spatial coherence effect.

We demonstrate that when a partially coherent beam with a Gaussian intensity distribution is focused by a lens, the desired partially coherent flat-topped intensity distribution or doughnut-shaped intensity distribution at the geometrical focus can be generated by choice of appropriate form of spectral degree of coherence. We provide a novel approach to beam shaping of a partially coherent beam and offer new schemes for their potential applications such as material processing, optical therapy, and optical tweezers.

Journal Article↗

The evaluation of recombinant, chimeric, tetravalent antihuman CD22 antibodies.

PURPOSE: The purpose of this study was to prepare chimeric antihuman CD22 tetravalent monoclonal antibodies (MAbs) with high functional affinity, long persistence in the circulation, increased antitumor activity, and conserved effector function in vitro. EXPERIMENTAL DESIGN: We investigated the association/dissociation rates of these tetravalent antibodies using CD22(+) Daudi lymphoma cells. We then tested their ability to interact with Fc receptors on a human cell line (U937), to mediate antibody-dependent cellular cytotoxicity with human natural killer cells, to bind human C1q, to inhibit the in vitro growth of CD22 Daudi cells, and to persist in the circulation. RESULTS: The rate of dissociation of the tetravalent MAbs versus the divalent antibody was considerably slower. These tetravalent MAbs inhibited the in vitro proliferation of CD22 Daudi cells at a concentration that was at least 100-fold lower than that of the divalent murine antibody. The tetravalent MAbs containing both the CH2 and CH3 domains and a chimeric recombinant divalent antibody bound similarly to Fc receptor, C1q, and mediate antibody-dependent cellular cytotoxicity equally well with human natural killer cells. The persistence in the circulation of chimeric tetravalent MAbs was considerably longer than that of chemical homodimers. CONCLUSIONS: The tetravalent anti-CD22 MAbs with intact Fc regions should make effective therapeutic agents for B-cell tumors.

Animals↗

Development of high throughput dispersive LC-ion mobility-TOFMS techniques for analysing the human plasma proteome.

A technique that combines ion mobility spectrometry (IMS) with reversed-phase liquid chromatography (LC), collision-induced dissociation (CID) and mass spectrometry (MS) has been developed. The approach is described as a high throughput means of analysing complex mixtures of peptides that arise from enzymatic digestion of protein mixtures. In this approach, peptides are separated by LC and, as they elute from the column, they are introduced into the gas phase and ionised by electrospray ionisation. The beam of ions is accumulated in an ion trap and then the concentrated ion packet is injected into a drift tube where the ions are separated again in the gas phase by IMS, a technique that differentiates ions based on their mobilities through a buffer gas. As ions exit the drift tube, they can be subjected to collisional activation to produce fragments prior to being introduced into a mass spectrometer for detection. The IMS separation can be carried out in only a few milliseconds and offers a number of advantages compared with LC-MS alone. An example of a single 21-minute LC-IMS-(CID)-MS analysis of the human plasma proteome reveals approximately 20,000 parent ions and approximately 600,000 fragment ions and evidence for 227 unique protein assignments.

Chromatography, Liquid↗

Antitumor effects of monoclonal antibody Fab' fragment-containing immunoconjugates.

OBJECTIVE: Using monoclonal antibody (mAb) Fab' fragment to develop mAb immunoconjugates for cancer. METHODS: Fab' fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DT), while Fab' fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by beta-mercaptoethanol. The conjugation between Fab' fragment and pingyangmycin (PYM), an antitumor antibiotic, was mediated by dextran T-40. Immunoreactivity of Fab'-PYM conjugates with cancer cells was determined by ELISA, and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay. Antitumor effects of the Fab'-PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. RESULTS: The molecular weight of Fab' fragment was approximately 53 kD, while the average molecular weight of Fab'-PYM conjugate was 170 kD. The Fab'-PYM conjugates showed immunoreactivity with antigen-relevant cancer cells and selective cytotoxicity against target cells. Administered intravenously, Fab'-PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. CONCLUSION: Fab'-PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth, suggesting its therapeutic potential in cancer treatment.

Animals↗

Synthesis and characterization of poly(butylene succinate-co-butylene malate): a new biodegradable copolyester bearing hydroxyl pendant groups.

A new biodegradable copolyester, poly(butylene succinate-co-butylene malate) P(BS-co-BM), has been preliminarily prepared with optically active centers and lateral hydroxyl functional groups via a four-step synthetic strategy. First, an optically active benzyl-protected dimethyl malate was synthesized from a starting material of (S)-dimethyl malate and purified with good yield. Then, copolyester poly(butylene succinate-co-benzyl-protected butylene malate), P(BS-co-BBM), was prepared through a skilled condensation copolymerization of the benzyl-protected dimethyl malate, dimethyl succinate, and 1,4-butanediol in the presence of titanium tetraisopropoxide as the catalyst. Finally, a Pd/C catalyzed hydrogenation was applied to eliminate the benzyl protection group in a mixed solution of THF and methanol; thus the target copolyester P(BS-co-BM) was attained. On the other hand, physical properties of the synthesized copolyesters were systematically characterized by means of nuclear magnetic resonance spectrometer, Fourier transformed infrared spectrometer, gel permeation chromatography, optical polarimeter, quantitative hydroxyl titration, and thermal analytical instruments. The experimental evidence demonstrated a successful construction of the product P(BS-co-BM) bearing lateral hydroxyl functional groups. It was also revealed that the lower BBM unit content was in the benzyl-protected optically active P(BS-co-BBM) copolyester, the higher melting point T(m), crystallinity, the broader molecular distribution, and the lower glass transition temperature T(g) would be detected, and these results can be accounted for the presence of bulky lateral benzyl moieties. In contrast, the deprotected product P(BS-co-55 mol % BM) showed a higher T(m), crystallinity and lower T(g) than its counterpart P(BS-co-55 mol % BBM). Interestingly, a thermal stability as high as that of the linear PBS was observed for P(BS-co-55 mol % BM) while a strong BBM unit content dependence of thermal stability was detected for the benzyl-protected copolyester P(BS-co-BBM)s. Therefore, these results may be beneficial for the new optically active P(BS-co-BM) bearing hydrophilic hydroxyl functional groups as a potential biomaterial.

Biodegradation, Environmental↗

Syntheses and physical characterization of new aliphatic triblock poly(L-lactide-b-butylene succinate-b-L-lactide)s bearing soft and hard biodegradable building blocks.

This study presents chemical syntheses and physical characterization of a new aliphatic poly(L-lactide-b-butylene succinate-b-L-lactide) triblock copolyester with soft and hard biodegradable building blocks. First, poly(butylene succinate) (PBS) prepolymers terminated with hydroxyl functional groups were synthesized through melt polycondensation from succinic acid and 1,4-butanediol. Further, a series of new PLLA-b-PBS-b-PLLA triblock copolyesters bearing various average PLLA block lengths were prepared via ring opening polymerization of L-lactide with the synthesized hydroxyl capped PBS prepolymer (Mn = 4.9 KDa) and stannous octanoate as the macroinitiator and catalyst, respectively. By means of GPC, NMR, FTIR, DSC, TGA, and wide-angle X-ray diffractometer (WAXD), the macromolecular structures and physical properties were intensively studied for these synthesized PBS prepolymer and PLLA-b-PBS-b-PLLA triblock copolyesters. 13C NMR and GPC experimental results confirmed the formation of sequential block structures without any detectable transesterification under the present experimental conditions, and the molecular weights of triblock copolyesters could be readily regulated by adjusting the feeding molar ratio of L-lactide monomer to the PBS macroinitiator. DSC measurements showed all single glass transitions, and their glass transition temperatures were found to be between those of PLLA and PBS, depending on the lengths of PLLA blocks. It was noteworthy that the segmental flexibilities of the hard PLLA blocks were found to be remarkably enhanced by the more flexible PBS block partner, and the PBS and PLLA building blocks were well mixed in the amorphous regions. Results of TGA analyses indicated that thermal degradation and stabilities of the PLLA blocks strongly depended on the average PLLA block lengths of triblock copolyesters. In addition, FTIR and WAXD results showed the coexistence of the assembled PLLA and PBS crystal structures when the average PLLA block length became larger than 7.8. These results may be beneficial for this new biodegradable aliphatic triblock copolyester to be applied as a potential biomaterial.

Biocompatible Materials↗

Novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s with functional carbonate building blocks. 1. Chemical synthesis and their structural and physical characterization.

This study presents chemical synthesis, structural, and physical characterization of novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s P(BS-co-CC) bearing functional carbonate building blocks. First, five kinds of six-membered cyclic carbonate monomers, namely, trimethylene carbonate (TMC), 1-methyl-1,3-trimethylene carbonate (MTMC), 2,2-dimethyl-1,3-trimethylene carbonate (DMTMC), 5-benzyloxytrimethylene carbonate (BTMC), and 5-ethyl-5-benzyloxymethyl trimethylene carbonate (EBTMC), were well prepared from ethyl chloroformate and corresponding diols at 0 degrees C in THF solution with our modified synthetic strategies. Then, a series of new P(BS-co-CC)s were synthesized at 210 degrees C through a simple combination of poly-condensation and ring-opening-polymerization (ROP) of hydroxyl capped PBS macromers and the prepared carbonate monomers, and titanium tetra-isopropoxide Ti(i-OPr)4 was used as a more suitable catalyst of 5 candidate catalysts which could concurrently catalyze poly-condensation and ROP. By means of NMR, GPC, FTIR, and thermal analytical instruments, macromolecular structures and physical properties have been characterized for these aliphatic poly(ester carbonate)s. The experimental results indicated that novel biodegradable P(BS-co-CC)s were successfully synthesized with number average molecular weight Mn ranging from 24.3 to 99.6 KDa and various CC molar contents without any detectable decarboxylation and that the more bulky side group was attached to a cyclic carbonate monomer, the lower reactivity for its copolymerization would be observed. The occurrences of 13C NMR signal splitting of succinyl carbonyl attributed to the BS building blocks could be proposed due to the randomized sequences of BS and CC building blocks. FTIR characterization indicated two distinct absorption bands at 1716 and 1733 approximately 1735 cm(-1), respectively, stemming from carbonyl stretching modes for corresponding BS and CC units. With regard to their thermal properties, it is seen that the synthesized P(BS-co-CC)s exhibited thermal degradation temperatures 10 approximately 20 degrees C higher than that of PBS. On the basis of the synthesized P(BS-co-BTMC)s, new aliphatic poly(butylene succinate-co-5-hydroxy trimethylene carbonate)s were further synthesized, bearing hydrophilic hydroxyl pendant functional groups through an optimized Pd/C catalyzed hydrogenation. These semi-crystalline new biodegradable aliphatic copolymers with tunable physical properties and functional carbonate building blocks might be expected as potential new biomaterials.

Biocompatible Materials↗