云南省卫生资源配置标准的弹性系数研究

目的　在进行云南省区域分类基础上制定云南省区域卫生资源配置标准标志值后 ,根据云南省各个地区的特点增加不同弹性系数。方法　采用流行病学研究方法 ,收集和分析云南省不同地州市 1990～ 1999年有关人口、社会经济状况及卫生经费的投入、居民健康状况、居民文化、生活水平、少数民族状况、旅游地区、边境线长短及贫困状况等资料。结果　研究结果表明曲靖地区、玉溪市、保山地区增加弹性系数最少 ,分别为 0 67%、 1 5 8%和1 68% ,怒江州、迪庆州和西双版纳州增加弹性系数最多 ,分别为 11 15 %、 10 2 5 %和 9 84 %。其它地区的弹性系数分别为昆明市 5 88% ,昭通地区 2 3 1% ,楚雄州 2 3 0 % ,红河州 7 0 3 % ,文山州 5 5 3 % ,思茅地区 7 4 3 % ,大理州4 94 % ,德宏州 6 78% ,丽江地区 4 3 5 % ,临沧地区 6 13 %。结论　云南省区域卫生配置标准的弹性系数研究为云南省卫生资源区域分类配置标准提供了科学依据 ,不同弹性系数体现了云南省不同地区的卫生资源区域分类配置标准的公平性、合理性及实用性     

Concentration-dependent metabolism of diazepam in mouse liver

Previous mouse liver studies with diazepam (DZ),N-desmethyldiazepam (NZ), and temazepam (TZ) confirmed that under first-order conditions, DZ formed NZ and TZ in parallel. Oxazepam (OZ) was generatedvia NZ and not TZ despite that preformed NZ and TZ were both capable of forming OZ. In the present studies, the concentration-dependent sequential metabolism of DZ was studied in perfused mouse livers and microsomes, with the aim of distinguishing the relative importance of NZ and TZ as precusors of OZ. In microsomal studies, theK _ms andV _maxs, corrected for binding to microsomal proteins, were 34 μM and 3.6 nmole/min per mg and 239 μM and 18 nmole/min per mg, respectively, forN-demthylation andC ₃-hydroxylation of DZ. TheK _ms andV _maxs forN-demethylation andC ₃-hydroxylation of TZ and NZ, respectively, to form OZ, were 58 μM and 2.5 nmole/min per mg and 311 μM and 2 nmole/min per mg, respectively. The constants suggest that at low DZ concentrations, NZ formation predominates and is a major source of OZ, whereas at higher DZ concentrations, TZ is the important source of OZ. In livers perfused with DZ at input concentrations of 13 to 35 μM, the extraction ratio of DZ (E{DZ}) decreased from 0.83 to 0.60. NZ was the major metabolite formed although its appearance was less than proportionate with increasing DZ input concentration. By contrast, the formation of TZ increased disporportionately with increasing DZ concentration, whereas that for OZ decreased and paralleled the behavior of NZ. Computer simulations based on a tubular flow model and thein vitro enzymatic parameters provided a poorin vitro-organ correlation. TheE{DZ}, appearance rates of the metabolites, and the extraction ratio of formed NZ (E{NZ, DZ}) were poorly predicted; TZ was incorrectly identified as the major precursor of OZ. Simulations with optimized parameters imporved the correlations and identified NZ as the major contributor of OZ. Saturation of DZN-demethylation at higher DZ concentrations increased the role of TZ in the formation of OZ. The poor aqueous solubility (limiting the concentration range of substrates usedin vitro), avid tissue binding and the coupling of enzymatic reactions in liver, favoring sequential metabolism, are possible explanations for the poorin vitro-organ correlation. This work emphasizes the complexity of the hepatic intracellular milieu for drug metabolism and the need for additional modeling efforts to adequately describe metabolite kinetics. This work was supported by the Medical Research Council of Canada (MA-9104).     

Attachment loss and serum antibody levels against autologous and reference strains of Actinobacillus actinomycetemcomitans in untreated localized juvenile periodontitis patients

Abstract Immunological data have been suggested to be a potential tool in the diagnosis, classification and monitoring of periodontal diseases. However, the role of circulating antibodies in periodontal patients is poorly understood. Patients suffering from localized juvenile periodontitis (LJP) are often reported to show high titers of serum IgG antibodies against Aetinobaeillus actinomycetemcomitans (A. actinomycetemcotnitans), but several affected patients do not. Most studies use well-known reference strains of the bacterium for testing against the patients' sera. The aim of the present investigation was to study the relationship between serum IgG antibody levels to autologous A. actinomycetemcomitans strains and clinical attachment loss (CAL). In addition, we wanted to assess the patients’serum titers against 4 well-known reference strains of the bacterium as well as their general potential immunoglobulin response. Intravenous blood samples were taken from 23 LJP patients and 10 healthy individuals, and autologous A. actinomycetemcomitans strains were cultured from 18 of the L.JP patients. CAL was measured at 4 different sites around ail present teeth and assessed as a % of teeth with at least 1 site moderately ≥2<5 mm) or severely (≥5 mm) involved. An enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the serum titers of IgG antibodies to A. actinomycetemcomitans antigens. No significant correlation was found between serum IgG antibody titers to autologous strains and CAL. However, there was a trend that low responders had more moderately affected teeth than had high responders and patients with undetectable A. actinomycetemcomitans levels, which is in agreement with a hypothetically protective role of the antibodies. The total counts of immunoglobulin assessed in all participants showed that the predominant class was IgG and the reference group displayed significantly less (p<0.05) IgG and IgG1 counts than the LJP patients. Both the reaction pattern against reference and autologous strains varied widely. We conclude that the specific antibody response against A. actinomycetemcomitans shows a weak correlation to clinical attachment levels in LJP patients.     

Determination of tissue optical properties by steady-state spatial frequency-domain reflectometry

A new non-invasive method to measure the optical properties of biological tissue is described. This method consists of illuminating the investigated sample with light which is spatially periodically modulated in intensity. The spatial modulation of the backscattered light and the diffuse reflectivity of the sample, both detected with an imaging technique, are used to deduce the absorption and reduced scattering coefficient from a table generated by Monte Carlo simulations. This principle has three major advantages: Firstly, it permits the immediate acquisition of the average values of the optical coefficients over a relatively large area (typ. 20 mm in diameter), thus avoiding the perturbations generated by small tissue heterogeneities; It also provides good flexibility for measuring the optical coefficients at various wavelengths and it does not require the use of a detector with a large dynamic range. The method was first validated on phantoms with known optical properties. Finally, we measured the optical properties of human skin at 400 nm, 500 nm, 633 nm and 700 nm in vivo.     

Synthesis,Physicochemical Properties,and Cytotoxicity of a Series of 5′-Ester Prodrugs of 5-Iodo-2′-deoxyuridine

Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU.     

广东省基层医疗卫生机构诊疗人次变化及影响因素的灰色关联分析

背景 我国分级诊疗制度建设已取得一定成效,但基层医疗卫生机构发展速度依旧相对缓慢。目的分析2013—2020年广东省基层医疗卫生机构诊疗人次的变化情况及影响因素,为政府深化分级诊疗制度建设提供参考依据。方法 于2021年12月,从2013—2015年《广东省卫生统计年鉴》、2016—2017年《广东省卫生和计划生育统计年鉴》、2018—2020年《广东省卫生健康统计年鉴》提取基层医疗卫生机构诊疗人次数据,作为参考序列;从《广东统计年鉴2021》提取人口数据及居民人均可支配收入,从2015—2017年《中国卫生和计划生育统计年鉴》和2018—2021年《中国卫生健康统计年鉴》提取基层医疗卫生机构财政补助收入和医疗保险参保人数,作为比较序列。采用灰色关联分析法评价各影响因素与基层医疗卫生机构诊疗人次的关联强度。结果 2013—2019年,广东省医院诊疗人次从33 459.2万人次增长至40 131.7万人次,年均增长3.08%,同期全省基层医疗卫生机构诊疗人次年均增长2.10%,2019年全省基层医疗卫生机构诊疗人次已达43 731.7万人次。2020年受新型冠状病毒感染疫情的影响,医院和...     

Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype–phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.     

Evidence for a glycerol pathway through aquaporin 1 (CHIP28) channels

Permeabilities to glycerol and small non-electrolytes of three Aquaporin 1 CHIP (AQP1) water channels were measured in AQP1 cRNA-injected Xenopus laevis oocytes and in human AQP1 channels reconstituted in proteoliposomes. By an osmotic swelling assay, significant increases of ethylene glycol, glycerol and 1,3-propanediol apparent permeability coefficients (P_solutes) were found in oocytes expressing human, rat and frog AQP1. p-Chloromercuribenzene sulphonate (PCMBS) and CuSO₄ inhibited, by 95% and 58% respectively, apparent glycerol permeability (P _gly) in oocytes expressing human AQP1. pCMBS inhibition was reversed by -mercaptoethanol and CuSO₄ inhibition was partly reversed by the Cu²⁺-binding peptide Gly-Gly-His. Tritiated glycerol uptakes confirmed the augmented P _gly value of AQP1 cRNA-injected oocytes. In contrast, no increases of urea, meso-erythritol, D- or L-threitol, xylitol and mannitol uptakes were detected. Stopped-flow light scattering experiments performed with human AQP1 proteoliposomes also revealed a much greater increase of P _gly than did those with protein-free liposomes; the initial rate of proteoliposomes also swelling was inhibited by 96.2% with HgCl₂ and by 72.5% with CuSO₄. In AQP1 cRNA-injected oocytes and in proteoliposomes, the value of the glycerol reflection coefficient was 0.74–0.80, indicating that water and glycerol share the same pathway. All these results provide strong evidence that water and certain small solutes permeate the AQP1 channels expressed at the surface of X. laevis oocytes or reconstituted in proteoliposomes. The urea exclusion suggests that the selectivity of the AQP1 channels not only depends on the size of the solutes but probably also on their flexibility and their ability to form H-bonds.     

Reciprocal translocation mosaicism in man

We report on an8-month-old girl with a de novo 5q/6q autosomal translocation with loss of the distal part of the long arm of chromosome 6 (6q23.3→6qter); clinical manifestations are peculiar craniofacial stigmata, truncal obesity and persisting hypotonia. The similarity with a previously reported patient with 6q interstitial deletion is discussed.     

Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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