Vision-dependent specification of cell types and function in the developing cortex.

The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ∼200 genes, including regulators of cell adhesion and synapse formation. One of these genes, Igsf9b, a vision-dependent gene encoding an inhibitory synaptic cell adhesion molecule, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell-type-specific gene expression programs.

Ig Superfamily Ligand and Receptor Pairs Expressed in Synaptic Partners in Drosophila.

Information processing relies on precise patterns of synapses between neurons. The cellular recognition mechanisms regulating this specificity are poorly understood. In the medulla of the Drosophila visual system, different neurons form synaptic connections in different layers. Here, we sought to identify candidate cell recognition molecules underlying this specificity. Using RNA sequencing (RNA-seq), we show that neurons with different synaptic specificities express unique combinations of mRNAs encoding hundreds of cell surface and secreted proteins. Using RNA-seq and protein tagging, we demonstrate that 21 paralogs of the Dpr family, a subclass of immunoglobulin (Ig)-domain containing proteins, are expressed in unique combinations in homologous neurons with different layer-specific synaptic connections. Dpr interacting proteins (DIPs), comprising nine paralogs of another subclass of Ig-containing proteins, are expressed in a complementary layer-specific fashion in a subset of synaptic partners. We propose that pairs of Dpr/DIP paralogs contribute to layer-specific patterns of synaptic connectivity.

EPHB2 as a key mediator of glioma progression: Insights from microenvironmental receptor ligand-related prognostic gene signature.

Malignant gliomas, characterized by pronounced heterogeneity, a complex microenvironment, and a propensity for relapse and drug resistaniguree, pose significant challenges in oncology. This study aimed to investigate the prognostic value of Ligand and Receptor related genes (LRRGs) within the glioma microenvironment. An intersection of 71 ligand-related genes (LRGs) and 2628 receptor-related genes (RRGs) yielded a total of 69 LRRGs. Utilizing the least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic RiskScore model comprising 28 LRRGs was constructed. The model demonstrated robust prognostic value, further validated in the TCGA-GBMLGG dataset. Subsequent analyses included differential gene expression, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment (GSEA), and gene set variation (GSVA) within RiskScore groups. Additionally, evaluations of PPI, mRNA-RBP, mRNA-TF, and mRNA-drug interaction networks were conducted. Four hub genes were identified through differential expression analysis of the 28 LRRGs across various GSE datasets. A multivariate Cox prognostic model was constructed for nomogram analysis, gene mutation analysis, and related expression distribution. This study underscores the role of LRRGs in intercellular communication within the glioma microenvironment and identifies four hub genes crucial for prognostic assessment in clinical glioma patients. These findings offer a potential evaluation framework for glioma patients, enhancing our understanding of the disease and informing future therapeutic strategies.

Cationic Oxidative Leaching Engineering Modulated In Situ Self-Reconstruction of Nickel Sulfide for Superior Water Oxidation.

Tuning the electroactive surface species of electrocatalysts remains a significant challenge for achieving highly efficient oxygen evolution reactions. Herein, we propose an innovative in situ leaching strategy, modulated by cationic oxidation, to achieve active self-reconstruction of these catalysts. Vanadium is introduced as a cation into Ni3S2 and oxidized under low oxidative potential, leading to subsequent leaching into the electrolyte and triggering self-reconstruction. The structural evolution from V-Ni3S2 to Ni(OH)2 and subsequently to NiOOH is identified by operando Raman as a three-step transition. In contrast, V-free Ni3S2 is unable to bypass the thermodynamically predicted nickel oxysulfide products to transform into active NiOOH. As a result, the self-restructured V-Ni3S2 only needs an ultralow overpotential of 155 mV at 10 mA cm-2, outperforming V-free Ni3S2 and many other advanced catalysts. This work provides new guidelines for manipulating in situ leaching to modulate the self-reconstruction of catalysts.

The Development of Receptive Field Tuning Properties in Mouse Binocular Primary Visual Cortex.

The mouse primary visual cortex is a model system for understanding the relationship between cortical structure, function, and behavior (Seabrook et al., 2017; Chaplin and Margrie, 2020; Hooks and Chen, 2020; Saleem, 2020; Flossmann and Rochefort, 2021). Binocular neurons in V1 are the cellular basis of binocular vision, which is required for predation (Scholl et al., 2013; Hoy et al., 2016; La Chioma et al., 2020; Berson, 2021; Johnson et al., 2021). The normal development of binocular responses, however, has not been systematically measured. Here, we measure tuning properties of neurons to either eye in awake mice of either sex from eye opening to the closure of the critical period. At eye opening, we find an adult-like fraction of neurons responding to the contralateral-eye stimulation, which are selective for orientation and spatial frequency; few neurons respond to ipsilateral eye, and their tuning is immature. Fraction of ipsilateral-eye responses increases rapidly in the first few days after eye opening and more slowly thereafter, reaching adult levels by critical period closure. Tuning of these responses improves with a similar time course. The development and tuning of binocular responses parallel that of ipsilateral-eye responses. Four days after eye opening, monocular neurons respond to a full range of orientations but become more biased to cardinal orientations. Binocular responses, by contrast, lose their cardinal bias with age. Together, these data provide an in-depth accounting of the development of monocular and binocular responses in the binocular region of mouse V1 using a consistent set of visual stimuli and measurements.SIGNIFICANCE STATEMENT In this manuscript, we present a full accounting of the emergence and refinement of monocular and binocular receptive field tuning properties of thousands of pyramidal neurons in mouse primary visual cortex. Our data reveal new features of monocular and binocular development that revise current models on the emergence of cortical binocularity. Given the recent interest in visually guided behaviors in mice that require binocular vision (e.g., predation), our measures will provide the basis for studies on the emergence of the neural circuitry guiding these behaviors.

A Bistable Triboelectric Nanogenerator for Low-Grade Thermal Energy Harvesting and Solar Thermal Energy Conversion.

Converting ubiquitous ambient low-grade thermal energy into electricity is of great significance for tackling the fossil energy shortage and environmental crisis but poses a considerable challenge. Here, a novel thermal-driven triboelectric nanogenerator (TD-TENG) is developed, which utilizes a bimetallic beam with a bi-stable dynamic feature to induce continuous mechanical oscillations, and the mechanical motion is then converted into electric power using a contact-separation TENG. The thermal process inside the device is systematically investigated and effective thermal management is conducted accordingly. After optimization, the TD-TENG can produce a power density of 323.9 mW m-2 at 59.5 °C, obtaining the highest record of TENG-based thermal energy harvesters. Besides, the first prototype of TENG-based solar thermal harvester is successfully demonstrated, with a power density of 364.4 mW m-2 . Moreover, the TD-TENG can harvest and dissipate the heat at the same time, exhibiting great potential in over-heated electronics protection as well as architectural energy conservation. Most importantly, the operation temperature range of the TD-TENG is tunable by adjusting the bimetal parameters, allowing the device a wide and flexible working thermal gradient. These unique properties validate the TD-TENG is a simple, feasible, cost-effective, and high-efficient low-grade thermal energy harvester.

Silencing of IRF7 ameliorates osteoarthritis by inhibiting chondrocyte pyroptosis via targeting FGF21.

Osteoarthritis (OA) is the most common joint disease which can lead to serious disability. Interferon regulatory factor 7 (IRF7) is a member of the interferon regulatory factor family. This study aimed to explore the function and potential mechanism of IRF7 in OA. Our results found that IRF7 was increased in LPS-stimulated C28/I2 chondrocytes and in OA mice established with medial menisco-tibial ligament (MMTL) transection. IRF7 silencing enhanced cell viability, reduced IL-18 and IL-1ß levels and suppressed cell apoptosis. IRF7 knockdown decreased ROS and LDH levels, and inhibited pyroptosis in LPS-treated chondrocytes. IRF7 negatively regulated FGF21 expression. FGF21 overexpression alleviated pyroptosis in LPS-stimulated chondrocytes. Knockdown of IRF7 improved OA injury in mice. In conclusion, our study demonstrates that silencing of IRF7 alleviates OA by inhibiting chondrocyte pyroptosis via upregulation of FGF21.

The Role of MicroRNAs in Hyperlipidemia: From Pathogenesis to Therapeutical Application.

Hyperlipidemia is a common metabolic disorder with high morbidity and mortality, which brings heavy burden on social. Understanding its pathogenesis and finding its potential therapeutic targets are the focus of current research in this field. In recent years, an increasing number of studies have proved that miRNAs play vital roles in regulating lipid metabolism and were considered as promising therapeutic targets for hyperlipidemia and related diseases. It is demonstrated that miR-191, miR-222, miR-224, miR-27a, miR-378a-3p, miR-140-5p, miR-483, and miR-520d-5p were closely associated with the pathogenesis of hyperlipidemia. In this review, we provide brief overviews about advances in miRNAs in hyperlipidemia and its potential clinical application value.

Application of collagen triple helix repeat containing-1 and mitotic spindle apparatus antibody in small cell lung cancer diagnosis.

BACKGROUND: The clinical significance of serum collagen triple helix repeat protein-1 (CTHRC1) and mitotic spindle apparatus antibody (MSA) in the diagnosis of small cell lung cancer (SCLC). METHODS: Of the 229 lung tumor patients selected, 62 patients were divided into SCLC, 94 patients with non-small cell lung cancer (NSCLC), and 73 patients with benign lung disease (BLD). The health controls (HC) had a span of 66 cases with normal physical condition. The serum extracted from each participator and enzyme-linked immunosorbent assay was adopted for measuring the serum CTHRC1 and MSA; in the meantime, automatic electrochemiluminescence immunoassay was used for the quantitative determination of serum NSA and CEA. And then, the differences in serum CTHRC1, MSA, NSE, and CEA were compared among involved groups. RESULTS: ① Compared with other groups, the concentrations of CTHRC1, MSA, and NSE showed a marked increase in the group of SCLC (all p < 0.01). Especially for SCLC patients with lymph node metastasis, CTHRC1 provided a notably higher level than those without metastasis. ② CTHRC1 and MSA established a diagnostic criterion with the specificity of 90.99% and 86.27% for SCLC, respectively. ③ In series, the specificity of CTHRC1 and NSE was the highest (99.30%), while MSA and NSE had the highest sensitivity (96.72%) in parallel. ④ Both CTHRC1 and MSA were hazardous factors interconnected with SCLC. CONCLUSION: Serum CTHRC1 and MSA had a more exciting prospect of application. When used in conjunction with NSE and CEA, they could optimize the clinical diagnosis value of SCLC.

Characteristics of ST11 KPC-2-producing carbapenem-resistant hypervirulent Klebsiella pneumoniae causing nosocomial infection in a Chinese hospital.

BACKGROUND: The purpose of our study is to analyze the microbiological and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) that causes nosocomial infection. METHODS: We collected the carbapenem-resistant K. pneumoniae (CRKP) strains that caused nosocomial infection in a hospital in China and collected the relevant clinical data. We characterized these strains for their antimicrobial and virulence-associated phenotype and genotype and analyzed the clonal relatedness. We screened hypervirulent strains and compared them with non-hypervirulent strains. RESULTS: We retrospectively analyzed 62 CRKP strains that caused nosocomial infection in a tertiary hospital within 1 year, of which 41 (41/62, 66.1%) CRKP were considered as CR-hvKP. All CR-hvKP strains were multi-drug resistance (MDR) and the vast majority of isolates (39/41, 95.1%) were ST11 KPC-2-producing strains. Two hypermucoviscous isolates and 4 capsular types were found in 41 CR-hvKP. Twenty-nine isolates (29/41, 70.7%) showed hypervirulence in Galleria mellonella infection model. PFGE showed that ST11-KL47 CR-hvKP and ST11-KL64 CR-hvKP exhibited a high degree of clonality, while non-hypervirulent strains were not significant. CR-hvKP had higher positive rates of blaKPC-2 and blaCTX-M-65 and higher levofloxacin resistance (p < 0.001, p = 0.005 and p = 0.046, respectively) when compared to the non-hypervirulent strains. There was no significant difference between the two groups in terms of in-hospital mortality (7/41, 17.1% vs 5/21, 23.8%, p = 0.743). CONCLUSION: Our research finds that ST11 KPC-2-producing CR-hvKP is the main type of CRKP that caused nosocomial infection, and clonal spread has occurred. We provide more information about CR-hvKP in health care.

Tumor necrosis factor-alpha stimulated gene-6: A biomarker reflecting disease activity in rheumatoid arthritis.

BACKGROUND: To explore the serum tumor necrosis factor-alpha stimulated gene-6 (TSG-6) level and its association with disease activity in rheumatoid arthritis (RA) patients. METHODS: We recruited 176 RA patients, 178 non-RA patients (lupus erythematosus, osteoarthritis, ulcerative colitis, ankylosing spondylitis and psoriasis) and 71 healthy subjects. Serum TSG-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). RA patients were divided into inactive RA and active RA groups by disease activity score of 28 joints based on C-reactive protein (DAS28-CRP). The receiver operating characteristic (ROC) curve and Spearman's rank correlation test analyzed the correlation between TSG-6 concentration and RA disease activity. RESULTS: Tumor necrosis factor-alpha stimulated gene-6 levels in the RA group were increased (p < 0.01). TSG-6 concentrations indicated an upward tendency with increased disease activity; The area under the curve (AUC) of TSG-6 for diagnosing RA and assessing the severity of RA were 0.78 and 0.80, respectively; The combination of TSG-6 and anti-mutated citrullinated vimentin antibodies (anti-MCV) (sensitivity:98.4%)improved the diagnostic accuracy of RA. Binary logistic regression analysis showed that TSG-6 was an independent risk factor related to the severity of RA, and OR (95% CI) was 1.2 (1.003-1.453). CONCLUSION: The TSG-6 levels in RA patients were elevated and related to disease activity. Therefore, TSG-6 may serve as a new potential biomarker for evaluating RA disease activity.

Prevention of breast cancer-related lymphoedema: Quality of clinical practice guidelines and variations in recommendations.

AIM: We aimed to evaluate the quality of clinical practice guidelines (CPGs) for breast cancer related lymphoedema (BCRL) and compare the similarities and differences in recommendations. BACKGROUND: Many CPGs of BCRL have been developed; however, their recommendations and quality are controversial. METHODS: Relevant papers were retrieved from electronic databases, professional associations and guideline development organizations, from 1 January 2015 to 30 September 2021. The Appraisal of Guidelines Research and Evaluation (AGREE) II instrument was used to evaluate the quality of the guidelines. Intraclass correlation coefficient (ICC) analysis was used to evaluate the overall consistency among evaluators. RESULTS: Eight CPGs were included. The ICC values evaluation for CPGs ranged from 0.76 to 0.95, with good consensus among evaluators. The highest median score was 68.75% (61.46, 72.22%) for clarity, and the lowest was 37.50% (25.78, 51.30%) for applicability. The NICE, ACS/ACSO and APTA CPGs were rated well in most areas. Professional health education, individualized exercise programme and regular surveillance are the main methods to prevent lymphoedema. CONCLUSION: In the past 6 years, the quality of BCRL guidelines has varied greatly, especially in the domains of rigour and applicability. Interrater agreement was excellent, but recommendation showed some inconsistencies in the details.

Immortal time bias exaggerates the effect of metformin on the risk of gastric cancer: A meta-analysis.

High heterogeneity has been reported among epidemiological studies exploring the relationship between metformin and the risk of gastric cancer. Immortal time bias might be one of the vital factors causing heterogeneity because of its widespread existence in pharmacological observational studies and it could severely exaggerate the drug's effectiveness. Immortal time bias could occur in an observational study if exposure status is determined based on a measurement or event that occurs after baseline. In this study, we aimed to assess whether immortal time bias is responsible for the false assumption that metformin reduces the risk of gastric cancer. We searched PubMed, Embase, Web of Science and Cochrane Library databases for relevant studies from the inception to August 9, 2020. The strength of the relationship was assessed using pooled relative risks (RRs) with corresponding 95% confidence intervals (95% CIs). Statistical analyses were carried out using a random-effects model. Pooled RR from 6 cohort studies with immortal time bias found a clear 33% reduced risk associated with metformin use (RR = 0.67, 95% CI = 0.59, 0.77; P < 0.001; I2 = 48.5%). However, pooled RR from 8 cohort studies without immortal time bias indicated no association between the use of metformin and gastric cancer risk (RR = 0.95, 95% CI = 0.85, 1.05; P = 0.317; I2 = 64.5%). From a univariate meta-regression model, the presence of immortal time bias was associated with a significant reduction of 29% in the effect estimate of metformin on gastric cancer risk (ratio of RR = 0.71, 95% CI = 0.58, 0.86; P = 0.002). This meta-analysis indicates that metformin use has no protective effect on gastric cancer risk. The relationship between metformin use and gastric cancer risk has been exaggerated as a result of the presence of immortal time bias. Further studies are required to confirm the results by controlling for immortal time bias based on appropriate study designs and statistical methods.

Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer.

PARP inhibitors are a group of inhibitors targeting poly(ADP-ribose) polymerases (PARP1 or PARP2) involved in DNA repair and transcriptional regulation, which may induce synthetic lethality in BRCAness tumors. Systematic analyzes of genomic sequencing in prostate cancer show that ~10%-19% of patients with primary prostate cancer have inactivated DNA repair genes, with a notably higher proportion of 23%-27% in patients with metastatic castration-resistant prostate cancer (mCRPC). These characteristic genomic alterations confer possible vulnerability to PARP inhibitors in patients with mCRPC who benefit only modestly from other therapies. However, only a small proportion of patients with mCRPC shows sensitivity to PARP inhibitors, and these sensitive patients cannot be fully identified by existing response prediction biomarkers. In this review, we provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.

Pigmentibacter ruber gen. nov., sp. nov., a novel bacterium of the family Silvanigrellaceae isolated from human blood.

A Gram-negative, aerobic, non-motile, pleomorphic, red-pigmented bacterium, designated HNSRY-1T, was isolated from the blood sample of a near drowning patient in Republic of China. Strain HNSRY-1T grew at 15-37 °C (optimum, 35 °C), with pH 6.0-8.0 (optimum, pH 7.0) and 0-1.5% (W/V) NaCl (optimum, 1%). The predominant fatty acids (> 5%) in HNSRY-1T cells are iso-C15:0, C17:0, C17:1 ω8c, C16:0, and C16:1 ω6c/C16:1 ω7c. The major respiratory quinone is MK-8. The polar lipids are phosphatidylglycerol, phosphatidylethanolamine, three unidentified lipids and four unidentified aminolipids. The 16S rRNA gene sequence-based phylogenetic analysis indicated that strain HNSRY-1T belonged to the family Silvanigrellaceae, forming a distinct phylogenetic line distantly related (< 96.4% sequence similarity) to known species of the family. The ANI values of strain HNSRY-1T compared to the closely related species were below the determined genus division threshold limit (92-94% ANI), and AAI values were lower than the determined genus division threshold limit (80% AAI). Whole genome sequencing revealed a genome size of 3.63 Mb with a DNA G + C content at 29.6%. The half-lethal dose of strain HNSRY-1T on KM mice is about 1.12 × 108 CFU/ml. Virulence gene analysis showed that the pathogenicity of HNSRY-1T may be related to tufA, htpB, katA, wbtL, wbtM, pseB, clpP, cheY, cheV3, acpXL, pilB, fliN, ggt, flgG, fliP, nueB, pseA, bioB and flil. Based on these findings from the polyphasic taxonomy studies, a novel genus and species of the family Silvanigrellaceae. Pigmentibacter ruber gen. nov., sp. nov. is proposed, with type strain HNSRY-1T (= KCTC 72920T = CGMCC 1.18525T).

Analysis of multiple organ damage and clinical immunological characteristics in systemic lupus erythematosus patients with hematologic involvement.

Objective: To investigate clinical immunological characteristics and imaging findings of multiple organ damage of systemic lupus erythematosus (SLE) patients with hematologic involvement. Methods: SLE patients diagnosed in the Second Affiliated Hospital of Nanchang University from June 2015 to March 2019 were selected, including 93 SLE patients with hematologic involvement and 68 SLE patients without hematologic involvement. Immunological indicators such as autoantibodies, immunoglobulin G (IgG), complement 4 (C4) and imaging data of several organs were measured respectively. The results were statistically analyzed. Results: SLE patients with hematologic involvement were more likely to have autoimmune hemolytic anemia (AIHA) (20.43%, P<0.05). The erythrocyte sedimentation rate (ESR) of SLE patients with hematologic involvement was 75.82 (±35.33) mm/h, IgG was 28.84 (±6.00) g/L and C4 was 0.073 (±0.031) g/L (P< 0.05). The area under the curve (AUC) of IgG was the highest among the above indicators (P<0.01). The positive anti-RO-52 antibody (OR=15.926, P<0.05) was an independent risk factor for pulmonary inflammatory lesions in SLE patients with hematologic involvement. Conclusion: Compared with the control group, abnormal immunological indicators and multiple organs damage are more obvious. Positive anti-RO-52 antibody may play an important role in the pathogenesis of pulmonary inflammation in SLE patients.

Tanshinone IIA Ameliorates Inflammation Response in Osteoarthritis via Inhibition of miR-155/FOXO3 Axis.

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder characterized by degeneration of the articular cartilage and joint destruction with an associated risk of mobility disability in elderly people. Although a lot of achievements have been made, OA is still regarded as an incurable disease. Therefore, the pathological mechanisms and novel therapeutic strategies of OA need more investigation. METHODS: MTT assay was conducted to measure the viability of chondrocytes after LPS treatment. Cell apoptosis was analyzed by annexin V/propidium iodide labeling. ELISA was used to determine the concentrations of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the culture supernatant of chondrocytes. The expression level of miR-155, IL-1ß, FOXO3, TNF-α, IL-6, caspase-3, and caspase-9 in chondrocytes was analyzed by RT-qPCR or Western blot. RESULTS: We found that LPS led to inflammatory responses, cell apoptosis, and increased miR-155 expression in human articular chondrocytes. Tanshinone IIA could inhibit LPS-induced inflammation and cell apoptosis of chondrocytes via regulating the expression of miR-155 and FOXO3. miR-155 directly targeted the 3'-UTR of FOXO3 to regulate its expression. CONCLUSIONS: Taken together, our data suggest tanshinone IIA ameliorates inflammation response in OA via inhibition of the miR-155/FOXO3 axis, and provide some evidences that tanshinone IIA could be designed and developed as a new promising clinical therapeutic drug for OA patients.

Determinants of successful guideline implementation: a national cross-sectional survey.

BACKGROUND: CPGs are not uniformly successful in improving care and several instances of implementation failure have been reported. Performing a comprehensive assessment of the barriers and enablers is key to developing an informed implementation strategy. Our objective was to investigate determinants of guideline implementation and explore associations of self-reported adherence to guidelines with characteristics of participants in China. METHODS: This is a cross-sectional survey, using multi-stage stratified typical sampling based on China's economic regional divisions (the East, the Middle, the West and the Northeast). 2-5 provinces were selected from each region. 2-3 cities were selected in each province, and secondary and tertiary hospitals from each city were included. We developed a questionnaire underpinned by recommended methods for the design and conduct of self-administered surveys and based on conceptual framework of guideline use, in-depth related literature analysis, guideline development manuals, related behavior change theory. Finally, multivariate analyses were performed using logistic regression to produce adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The questionnaire consisted of four sections: knowledge of methodology for developing guidelines; barriers to accessing guideline; barriers to guideline implementation; and methods for improving guideline implementation. There were 1732 participants (87.3% response rate) from 51 hospitals. Of these, 77.2% reported to have used guidelines frequently or very frequently. The key barriers to guideline use were lack of education or training (46.2%), and overly simplistic wording or overly broad scope of recommendations (43.8%). Level of adherence to guidelines was associated with geographical regions (the northeast P < 0.001; the west P = 0.02; the middle P < 0.001 compared with the east), hospital grades (P = 0.028), length of practitioners' practice (P = 0.006), education background (Ph.D., P = 0.027; Master, P = 0.002), evidence-based medicine skills acquired in work unit (P = 0.012), and medical specialty of practitioner (General Practice, P = 0.006; Surgery, P = 0.043). CONCLUSION: Despite general acknowledgement of the importance of guidelines, the use of guidelines was not as frequent as might have been expected. To optimize the likelihood of adherence to guidelines, guideline implementation should follow an actively developed dissemination plan incorporating features associated with adherence in our study.

High density lipoprotein in rheumatoid arthritis: emerging role in predicting inflammation level and osteoporosis occurrence.

Dyslipidaemia is common in patients with rheumatoid arthritis (RA) appearing both early and advanced stages of the disease. A retrospective study was designed to explore the clinical significance of high density lipoprotein (HDL) in Chinese patients with RA. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were compared between RA patients complicated with osteoporosis (OP) and without OP, using logistic regression and ROC curve to analyse the association of HDL with OP. C reactive protein (CRP), erythrocyte sedimentation rate(ESR), rheumatoid factor(RF), anti-cyclic citrulline polypeptide antibody (anti-CCP), 28 joints disease activity(DAS28) as well as organ involvement rates were then analysed between RA patients with different HDL levels. Serum levels of HDL were 1.2 ± 0.3 mmol/L in RA patients complicated with OP, significantly higher than those without OP; HDL was a risk factor for RA patients with OP, OR (95% CI) being 10.2 (4.5-23.0) after adjusting for gender, age and body mass index(BMI). RA patients with HDL ≤ 1.04 mmol/L had significantly higher levels of CRP, ESR, DAS28 and cardiovascular disease (CVD) incidence rate, yet OP incidence rate was lower. HDL was a predictor of RA-related OP, indicating potential value as predictor of disease complications in RA patients.

Practical application of Six Sigma management in analytical biochemistry processes in clinical settings.

BACKGROUND: Six Sigma methodology with a zero-defect goal has long been applied in commercial settings and was utilized in this study to assure/improve the quality of various analytes. METHODS: Daily internal quality control (QC) and external quality assessment data were collected and analyzed by calculating the sigma (σ) values for 19 analytes based on the coefficient of variation, bias, and total error allowable. Standardized QC sigma charts were established with these parameters. Quality goal index (QGI) analysis and root cause analysis (RCA) were used to discover potential problems for the analytes. RESULTS: Five analytes with σ ≥ 6 achieved world-class performance, and only the Westgard rule (13s ) with one control measurement at two QC material levels (N2) per QC event and a run size of 1000 patient samples between QC events (R1000) was needed for QC. In contrast, more control rules (22s /R4s /41s ) along with high N values and low R values were needed for quality assurance for five analytes with 4 ≤ σ < 6. However, the sigma levels of nine analytes were σ < 4 at one or more QC levels, and a more rigorous QC procedure (13s /22s /R4s /41s /8x with N4 and R45) was implemented. The combination of QGI analysis and RCA further revealed inaccuracy or imprecision problems for these analytes with σ < 4 and discovered five aspects of potential causes considered for quality improvement. CONCLUSIONS: Six Sigma methodology is an effective tool for evaluating the performance of biochemical analytes and is conducive to quality assurance and improvement.