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PubMed2005

[Combined use of factor analysis and cluster analysis in classification of traditional Chinese medical syndromes in patients with posthepatitic cirrhosis].

OBJECTIVE: To explore the significance of the combination of factor analysis and systematic cluster analysis in classification of traditional Chinese medical syndromes in patients with posthepatitic cirrhosis, and to provide a scientific basis for the criterion of the classification. METHODS: We designed a clinical questionnaire according to the clinical characteristics and the demands of traditional Chinese medical information collection for patients with posthepatitic cirrhosis. By means of clinical epidemiological research, with the four diagnosis methods for clinical information collection of traditional Chinese medicine, symptoms, physical signs, tongue conditions and pulse conditions in 310 patients with posthepatitic cirrhosis were collected, and the characteristics of traditional Chinese medical syndromes in these patients were explored with statistical methods, such as factor analysis, varimax and systematic cluster analysis. RESULTS: Analyzed by factor analysis and systematic cluster analysis with SPSS 11.0, the traditional Chinese medical syndromes in 287 of the 310 cases (92.58%) of posthepatitic cirrhosis could be classified. The syndromes could be divided into 7 categories, which were internal accumulation of damp-heat (55 cases), insufficiency of the spleen with overabundance of dampness (74 cases), accumulation of blood stasis plus deficiency of liver-yin and kidney-yin (73 cases), accumulation of blood stasis plus deficiency of both blood and qi (40 cases), deficiency of both blood and qi (16 cases), deficiency of yin and blood heat (6 cases) and stagnation of the liver-qi and deficiency of the spleen (23 cases). The traditional Chinese medical syndromes in the other 23 cases could not be classified. CONCLUSIONS: The clinical information collected with the four diagnostic methods of traditional Chinese medicine can be classified into different categories with the factor analysis and systematic cluster analysis. The factor analysis and systematic cluster analysis can reveal the characteristics and regularity of traditional Chinese medical syndromes in patients with posthepatitic cirrhosis in a way, and have value in researching the syndromes of traditional Chinese medicine.

Adult↗

PubMed2002

Ion suppression effects in liquid chromatography-electrospray-ionisation transport-region collision induced dissociation mass spectrometry with different serum extraction methods for systematic toxicological analysis with mass spectra libraries.

Ion suppression effects during electrospray-ionsation mass spectrometry (ESI-MS) caused by different sample preparation procedures for serum were investigated. This topic is of importance for systematic toxicological analysis for which LC-ESI-MS has been developed with transport-region collision-induced dissociation (ECI-CID) and mass spectra library searching. With continuous postcolumn infusion of two test compounds-codeine and glafenine-the ion suppression effects of extracted biological matrix obtained after a standard liquid-liquid extraction, a mixed-mode solid-phase extraction (SPE) method, a protein precipitation method and a combination of precipitation with polymer-based mixed-mode SPE have been investigated. Extracted ion chromatograms of codeine ([M+H](+), m/z 300) and glafenine ([M-H](-), m/z 371) were used for monitoring ion suppression. Severe ion suppression effects for codeine and glafenine were detected in positive and in negative ionisation modes, respectively, in the LC-front peak after serum clean-up with SPE (acid/neutral fraction) and protein precipitation as well as with protein precipitation combined with SPE. Less ion suppression of codeine in positive mode was found with liquid-liquid extraction of serum samples. No ion suppression was detected with the second fraction of the mixed-mode SPE (using RP-C(8) and cation-exchange phase) in both ionisation modes. All suppression effects were caused by polar and unretained matrix components, which were present after extraction and/or protein precipitation. However, no specific ion suppression was seen after elution of the polar LC-front throughout the whole gradient. It could be demonstrated, that ion suppression is not generally present at any retention time when using reversed-phase HPLC with rather long gradient programs, but may play an important role in case of high-throughput LC-MS analysis, when the analyte is not separated from the LC-front, or in flow injection analysis without chromatographic separation.

Chromatography, Liquid↗

PubMed1997

Systematic mutational analysis of the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor cytoplasmic domain. An acidic cluster containing a key aspartate is important for function in lysosomal enzyme sorting.

We have used systematic mutational analysis to identify signals in the 166-residue murine cation-independent mannose 6-phosphate/insulin-like growth factor II receptor cytoplasmic domain required for efficient sorting of lysosomal enzymes. Alanine cluster mutagenesis on all conserved residues apart from the endocytosis signal demonstrates that the major sorting determinant is a conserved casein kinase II site followed by a dileucine motif (157DDSDEDLL164). Small deletions or additions outside this region have severe to mild effects, indicating that context is important. Single residue mutagenesis indicates that cycles of serine phosphorylation/dephosphorylation are not obligatory for sorting. In addition, the two leucine residues and four of the five negatively charged residues can readily tolerate conservative substitutions. In contrast, aspartate 160 could not tolerate isoelectric or isosteric substitutions, implicating it as a critical component of the sorting signal.

Amino Acid Sequence↗

PubMedDate not supplied

Screening procedure for detection of antidepressants of the selective serotonin reuptake inhibitor type and their metabolites in urine as part of a modified systematic toxicological analysis procedure using gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) screening procedure was developed for detection of selective serotonin reuptake inhibitors (SSRIs) in urine as part of a systematic toxicological analysis procedure. After acid hydrolysis of one aliquot of urine, another aliquot was added. The mixture was then liquid-liquid extracted at pH 8-9, acetylated, and GC separated. Using mass chromatography with the ions m/z 58, 72, 86, 173, 176, 234, 238, and 290, the possible presence of SSRIs and/or their metabolites could be indicated. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with the reference spectra recorded during this study. The overall recoveries of citalopram, sertraline, and paroxetine ranged between 60 and 80%, and those of fluoxetine and fluvoxamine, which were destroyed during acid hydrolysis, were between 40 and 45%. The coefficients of variation were less than 10-20%, and the limit of detection was at least 100 ng/mL (signal-to-noise ratio = 3). This method allowed the detection of therapeutic concentrations of citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline in human urine samples.

Antidepressive Agents, Second-Generation↗

PubMedDate not supplied

A simple automated procedure for the detection and identification of peaks in gas chromatography--continuous scan mass spectrometry. Application to systematic toxicological analysis of drugs in whole human blood.

Gas chromatography-mass spectrometry (GC-MS), which combines the separation power of GC with the power of MS for the identification of unknown compounds, possesses high potential in systematic toxicological analysis (STA). Different factors, however, do not allow this potential to be fully exploited. Between them, the low selectivity of the mass spectrometer operating in continuous scan plays a critical role, in many cases precluding the possibility of selecting mass spectra in the total ion chromatogram (TIC) sufficiently clean for a positive identification by library search, even when using reverse search algorithms. Moreover, the large amount of information contained in GC-MS data file that results from the analysis of a biological extract makes the efforts of manual search almost useless and requires the availability of reliable methods for the automated detection and identification of peaks in a TIC. In this paper, a simple procedure that improves the performance of a bench-top GC-MS system in the purification of mass spectra of coeluting compounds and that can be easily combined with the automated processing of a GC-MS data file is described. It is based on the subtraction of the intensities of successive pairs of scans in the TIC, on the detection of positive and negative peaks in the transformed chromatograms, and on the search of the corresponding background-subtracted electron ionization mass spectra against reference libraries. In order to evaluate the proposed procedure, GC-MS data files obtained for the analysis of extracts of blank whole blood spiked with more than 100 drugs, poisons, and their metabolites at a concentration of 0.5 mg/L were used. Compared with the search of the raw TICs, the proposed procedure increased the number of identified substances and, in many cases, obtained higher match quality values for identification.

Amitriptyline↗

PubMed2005

An analysis of systematic reviews indicated low incorpororation of results from clinical trial quality assessment.

OBJECTIVE: We investigated the frequency of quality assessment of randomized controlled trials within systematic reviews and the incorporation of the quality assessment in the analysis. STUDY DESIGN AND SETTING: We included new systematic reviews of at least five trials of therapeutic or preventive interventions that appeared in issue 2, 2003, of the Cochrane Database of Systematic Reviews. All systematic reviews in the 2002 issues of the Annals of Internal Medicine, BMJ, JAMA, and Lancet were identified in Pubmed. All reviews were assessed under unblinded conditions using preprinted extraction forms. RESULTS: Trial quality was assessed in all Cochrane reviews and most (74%) of the paper reviews. When we excluded 11 paper reviews that were also published as Cochrane review, the percentage remained similar (67%). Fifty percent of all Cochrane reviews and 61% of all paper reviews incorporated the results of the quality assessment in the analysis. CONCLUSION: Half of the reviews did not incorporate the results of the quality assessment in the analysis. Authors, peer-reviewers, and editors should no longer focus exclusively on whether quality assessment has been performed but should also concentrate on incorporation of quality assessments in the analysis of the systematic review.

Databases, Bibliographic↗

PubMed2026

A Bibliometric Analysis of Systematic Reviews in the Field of Ankylosing Spondylitis from 2007 to 2025.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease and the most common clinical form of spinal arthritis. Over the past decades, tremendous progress has been made in systematic reviews on AS. This study aimed to conduct a bibliometric analysis of AS-related meta-analyses to visualize the hotspots and trends in the field. METHODS: A comprehensive search was conducted for publications of AS meta-analysis from 2007 to 2025 using the Web of Science Core Collection database. Bibliometric analysis was performed using the Bibliometrix software package, VOSviewer, and CiteSpace. RESULTS: In total, 1073 articles were identified, and the number of relevant publications showed annual growth. China, the USA, and England were the most productive countries. Annals of the Rheumatic Diseases was the most productive journal (54, 10.65%), Pan Faming was the most productive author (23, 4.54%), and Anhui Medical University (45, 8.88%) was the most productive institution. High-frequency keywords were mainly grouped into five themes: complications, biologics, physical therapy exercises, gut microbiota, and analytical methods. DISCUSSION: This first bibliometric analysis of AS-related EBM research showed a 20-year upward trend in AS meta-analyses, consistent with prior studies. CiteSpace revealed that China (top since 2014) and the USA led in publications (53 countries) but had limited collaboration. Pan Faming (23 articles) was the most active author, and Annals of the Rheumatic Diseases published the most articles. Keyword analysis identified five themes (e.g., AS complications, biologics) and research frontiers: pre-2012 genome-AS links, post-2012 multi-center RCTs, and the recent focus on AS patients' HRQoL. Limitations included database and English-language bias; future meta-analyses should adopt standardized outcomes. CONCLUSION: In recent years, there has been a remarkable surge in the number of meta-analyses on AS. This significant increase underscores the importance of this research area. Studies in this field have mainly focused on several key aspects: risk factors, network meta-analysis, and quality- of-life studies. These findings are highly valuable for understanding advancements in ASrelated research and can also encourage researchers and clinicians to focus on both effective medical treatments and the well-being of AS patients.

Spondylitis, Ankylosing↗

PubMed1994

Systematic mutational analysis of the yeast beta-tubulin gene.

A systematic strategy was used to create a synoptic set of mutations that are distributed throughout the single beta-tubulin gene of Saccharomyces cerevisiae. Clusters of charged amino acids were targeted for mutagenesis and converted to alanine to maximize alterations on the protein's surface and minimize alterations that affect protein folding. Of the 55 mutations we constructed, three confer dominant-lethality, 11 confer recessive-lethality, 10 confer cold-sensitivity, one confers heat-sensitivity, and 27 confer altered resistance to benomyl. Only 11 alleles give no discernible phenotype. In spite of the fact that beta-tubulin is a highly conserved protein, three-fourths of the mutations do not destroy the ability of the protein to support the growth of yeast at 30 degrees C. The lethal substitutions are primarily located in three regions of the protein and presumably identify domains most critical for beta-tubulin function. Interestingly, most of the conditional-lethal alleles produce specific defects in spindle assembly at their restrictive temperature; cytoplasmic microtubules are relatively unaffected. The exceptions are two mutants that contain abnormally long cytoplasmic microtubules. Mutants with specific spindle defects were not observed in our previous collection of beta-tubulin mutants and should be valuable in dissecting spindle function.

Alleles↗

PubMed1998

Detection of 4-hydroxycoumarin anticoagulants and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation.

A gas chromatography-mass spectrometry (GC-MS) procedure was developed for the detection of 4-hydroxycoumarin anticoagulants and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons after extractive methylation. The part of the phase-transfer catalyst remaining in the organic phase was removed by solid-phase extraction on a diol phase. The compounds were separated by capillary GC and identified by computerized MS in the full scan mode. Using mass chromatography with the ions m/z 291, 294, 295, 309, 313, 322, 324, 336, 343 and 354, the possible presence of 4-hydroxycoumarin anticoagulants and/or their metabolites could be indicated. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with the reference spectra recorded during this study. This method allowed the detection of therapeutic concentrations of phenprocoumon and warfarin in human urine samples. In absence of human urine, acenocoumarol, coumachlor, coumatetrayl, pyranocoumarin (cyclocumarol) could be detected only in rat urine.

4-Hydroxycoumarins↗

PubMedDate not supplied

Screening procedure for detection of dihydropyridine calcium channel blocker metabolites in urine as part of a systematic toxicological analysis procedure for acidic compounds by gas chromatography-mass spectrometry after extractive methylation.

A gas chromatographic-mass spectrometric (GC-MS) screening procedure was developed for the detection of dihydropyridine calcium channel blocker ("calcium antagonist") metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons after extractive methylation. The part of the phase-transfer catalyst remaining in the organic phase was removed by solid-phase extraction on a diol phase. The compounds were separated by capillary GC and identified by computerized MS in the full scan mode. Using mass chromatography with the ions m/z 139, 284, 297, 298, 310, 312, 313, 318, 324, and 332, the possible presence of calcium channel blocker metabolites could be indicated. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with the reference spectra recorded during this study. This method allowed the detection of therapeutic concentrations of amlodipine, felodipine, isradipine, nifedipine, nilvadipine, nimodipine, nisoldipine, and nitrendipine in human urine samples. Because urine samples from patients treated with nicardipine were not available, the detection of nicardipine in rat urine was studied. The overall recovery ranged between 67 and 77% with a coefficient of variation of less than 10%, and the limit of detection was at least 10 ng/mL (signal-to-noise ratio = 3) in the full-scan mode.

Acids↗

PubMed2026

The effectiveness of digital health interventions for type 2 diabetes in underserved populations: A systematic review and meta-analysis.

This systematic review and meta-analysis of 12 randomized controlled trials (1835 participants) evaluated whether digital health interventions (DHIs) improve glycemic control among underserved adults with type 2 diabetes (T2D), including racial/ethnic minority, low-income, Medicaid-insured, rural, and low-health-literacy populations. Searches of PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 20, 2025 identified eligible parallel-group randomized controlled trials reporting change in hemoglobin A1c (HbA1c). Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias 2 tool. Random-effects meta-analysis showed that DHIs produced a modest but statistically significant HbA1c reduction versus control (mean difference, -0.37 %age points; 95% CI, -0.44 to -0.30; P < .0001; equivalent to -4.0 mmol/mol). Heterogeneity was moderate-to-substantial (I² = 69.9%). Subgroup analyses suggested directionally similar effects by population group and intervention modality, but interpretation was limited by study-level data and the small number of trials. Funnel-plot inspection and Egger's test (P = .31) did not suggest major small-study effects, although power was limited. Overall certainty for HbA1c was moderate. DHIs may support more equitable diabetes care when implemented with cultural tailoring, language access, digital-literacy support, and technology-access safeguards.

Humans↗

PubMedDate not supplied

Screening procedure for detection of non-steroidal anti-inflammatory drugs and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesic and anti-rheumatic drugs, and they are often misused. A gas chromatographic-mass spectrometric (GC-MS) screening procedure was developed for their detection in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons after extractive methylation. The compounds were separated by capillary GC and identified by computerized MS in the full-scan mode. Using mass chromatography with the ions m/z 119, 135, 139, 152, 165, 229, 244, 266, 272, and 326, the possible presence of NSAIDs and their metabolites could be indicated. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with the reference spectra recorded during this study. This method allowed the detection of therapeutic concentrations of acemetacin, acetaminophen (paracetamol), acetylsalicylic acid, diclofenac, diflunisal, etodolac, fenbufen, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, indometacin, kebuzone, ketoprofen, lonazolac, meclofenamic acid, mefenamic acid, mofebutazone, naproxen, niflumic acid, phenylbutazone, suxibuzone, tiaprofenic acid, tolfenamic acid, and tolmetin in urine samples. The overall recoveries of the different NSAIDs ranged between 50 and 80% with coefficients of variation of less than 15% (n = 5), and the limits of detection of the different NSAIDs were between 10 and 50 ng/mL (S/N = 3) in the full-scan mode. Extractive methylation has proved to be a versatile method for STA of various acidic drugs, poisons, and their metabolites in urine. It has also successfully been used for plasma analysis.

Acids↗

PubMed1995

"Meta-analysis: statistical alchemy for the 21st century": discussion. A plea for a more balanced view of meta-analysis and systematic overviews of the effect of health care interventions.

The paper discusses some of the most common criticisms to meta-analysis presented by Professor Feinstein in this Conference. As many of the points raised in his contributions are not new, a critique to them is presented in the context of the type of contribution given by systematic reviews (meta-analysis) to the analysis of the effects of health care interventions. After discussing some terminological issues, the paper challenges Feinsteins' arguments indicating that meta-analysis is inherently faulted on four grounds: (a) reproducibility, (b) precision, (c) suitable extrapolation, (d) fair comparison. Each point is discussed providing examples drawn from the published literature with a view to indicate that--despite their current limitations--systematic reviews are a necessary step to synthesize information, orient clinical research and help produce practice guidelines.

Bias↗

PubMed1996

RAPD analysis of systematic relationships among the Cervidae.

We investigated the possible application of RAPD (Random Amplified Polymorphic DNA) analysis to the study of the systematic relationships of five cervid taxa. Amplifications with eight different primers gave reproducible electrophoretic patterns which could be regarded as a data-set consisting of monomorphic and polymorphic characters. Some of these characters are species- and subspecies-specific. Band-sharing analysis and numerical taxonomy methods allowed us to generate a phenetic tree. Our results point out new possible systematic considerations within the examined taxa.

Animals↗

PubMed2005

Systematic deletion analysis of fission yeast protein kinases.

Eukaryotic protein kinases are key molecules mediating signal transduction that play a pivotal role in the regulation of various biological processes, including cell cycle progression, cellular morphogenesis, development, and cellular response to environmental changes. A total of 106 eukaryotic protein kinase catalytic-domain-containing proteins have been found in the entire fission yeast genome, 44% (or 64%) of which possess orthologues (or nearest homologues) in humans, based on sequence similarity within catalytic domains. Systematic deletion analysis of all putative protein kinase-encoding genes have revealed that 17 out of 106 were essential for viability, including three previously uncharacterized putative protein kinases. Although the remaining 89 protein kinase mutants were able to form colonies under optimal growth conditions, 46% of the mutants exhibited hypersensitivity to at least 1 of the 17 different stress factors tested. Phenotypic assessment of these mutants allowed us to arrange kinases into functional groups. Based on the results of this assay, we propose also the existence of four major signaling pathways that are involved in the response to 17 stresses tested. Microarray analysis demonstrated a significant correlation between the expression signature and growth phenotype of kinase mutants tested. Our complete microarray data sets are available at http://giscompute.gis.a-star.edu.sg/~gisljh/kinome.

Biological Evolution↗

PubMed2006

Development of a high performance liquid chromatographic method for systematic quantitative analysis of chemical constituents in rhubarb.

HPLC methods for the systematic determination of 30 compounds in Rhei Rhizoma (rhubarb) were developed. Using a combination of mobile phase gradient conditions and UV detection at 280 nm, all 30 compounds were separated satisfactorily with low detection limits (0.05-2 microg/ml). The developed methods provided a reliable calibration curve for each compound. By adopting these methods, the determination of 30 compounds in three kinds of rhubarb samples, derived from Rheum tanguticum, R. palmatum and R. officinale, was achieved. The constituent pattern of each rhubarb was clearly characterized through the quantitative composition of 30 major constituents of rhubarb.

Calibration↗

PubMed1998

[The application of solid phase extraction for systematic toxicological analysis of abuse drugs].

A new column was developed in this research. It contains a proprietary bonded silica sorbent that exhibits mixed extraction mechanism. A single-column solid-phase extraction procedure was also developed for the screening of acidic, neutral and basic abuse drugs. The recovery of all 7 tested drugs exceeded 60%. The extraction mechanism for different abuse drugs on the new column was explored and was compared with on other columns. It is suggested that this column be effective in systematic toxicological analysis and better than other columns.

Antipsychotic Agents↗

PubMed1996

Systematic mutational analysis revealing the functional domain organization of Escherichia coli nucleoid protein H-NS.

The Escherichia coli H-NS protein is one of the major constituents of the nucleoid structure. This protein has been implicated not only in the compact organization of the nucleoid structure, but also in the global regulation of gene expression. H-NS negatively regulates the transcription of a number of apparently unlinked genes on the chromosome, suggesting that it functions as a global transcriptional repressor. In this study, on systematic mutational analysis of hns, three distinct functional domains were found in H-NS, which appear to be responsible for DNA-binding, transcriptional repression and protein-protein interaction (dimerization and/or oligomerization), respectively. We first isolated a number of hns mutations which resulted in derepression of the proVWX operon. These included 20 independent missence mutations each resulting in a single amino acid substitution, and six nonsense mutations each giving a C-terminally truncated form of H-NS. The substituted amino acids were revealed to be located non-randomly in the primary sequence of H-NS. This set of hns mutants was examined extensively in terms of phenotypes and biochemical properties. Based on the in vivo and in vitro results, together with the locations of the altered amino acids, three distinct functional domains were identified in H-NS. Mutations in the C-terminal domain resulted in a loss of its DNA-binding ability, suggesting that this domain is directly involved in its binding to DNA. The N-terminal domain was suggested to be involved in the ability to repress transcription. Mutations in this region abolished its ability to repress the transcription of proV, in vivo and in vitro, without loss of its DNA-binding activity. None of the mutants examined was impaired in the formation of a dimer and/or oligomers, suggesting that the central region of H-NS is involved in oligomerization. These results are discussed with special reference to the molecular mechanism underlying the function of H-NS as a transcriptional repressor. In addition, expression of the bgl operon was found to be affected by only a subset of hns mutations in a highly allele-specific manner. This finding is also addressed with regard to a unique regulatory mechanism (i.e. silencing) for the bgl operon, which is partly mediated by H-NS.

Amino Acid Sequence↗