[Bone damage in osteoporotic fractures].

Osteoporotic fracture is fundamentally different from traumatic fracture. It is a pathological fracture based on the skeletal system in the state of osteoporosis, and the essence of its lesion is the decline of bone strength. Bone strength is influenced by a variety of factors, including the material properties and tissue structure of the bone, as well as muscle load. The pathological changes of osteoporotic fracture both of the damage of bone mass and bone quality. After the occurrence of osteoporotic fracture, even successful surgical treatment cannot prevent the further aggravation of osteoporotic bone damage. In this paper, the material properties and tissue structure damage of osteoporotic fractures are elaborated, and it is emphasized to clarify and pay attention to these bone lesions and their risks. Anti-osteoporosis treatment is of great importance to improve the clinical efficacy of osteoporosis and fracture intervention and prevent the occurrence of re-fractures.

Metabolic disposition of [14 C]-abivertinib, an epidermal growth factor receptor tyrosine kinase inhibitor: Role of glutathione conjugation.

AIMS: To determine the absorption, distribution, metabolism and excretion of abivertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seven patients with advanced NSCLC were given a single 200 mg/83 µCi oral suspension of [14 C]-abivertinib. Blood, urine and faeces were collected. Mass balance of radioactivity, the pharmacokinetics of abivertinib, and the total radioactivity were determined. Metabolite profiling and characterisation were performed. RESULTS: The mean recovery was 82.16%, with 2.38 and 79.78% of the radioactive dose excreted in urine and faeces, respectively. The unchanged abivertinib was the major radioactive component detected in plasma within the first 24 hours after dosing, accounting for 59.17% of the total drug-related radioactivity. Abivertinib in urine accounted for only 0.96% of the administered dose, whereas in faeces it accounted for 33.36%. Eight metabolites were detected and characterised in plasma, among which MII-7, a product of cysteine glycine conjugate, was the only circulating metabolite, accounting for approximate 10.6% of the total drug-related exposure. MII-2 (an abivertinib cysteine-glycine adduct) and M7 (a reduced product of abivertinib) were the 2 major metabolites in the excreta, accounting for 20.0 and 12.4%, respectively, of the drug-related radioactivity in faeces. CONCLUSION: Following a single oral administration, the unchanged abivertinib was the predominant drug-related material in plasma, urine and faeces. The drug-related materials were primarily eliminated via the faecal route. Direct glutathione conjugation of abivertinib played a significant role in the metabolic clearance and metabolite exposure of abivertinib.

Development and evaluation of armored RNA-based standards for quantification of BCR-ABL1p210/p190 fusion gene transcripts.

BACKGROUND: Standards play an important role in detection of the BCR-ABL1 fusion gene (FG) transcript. However, the standards widely used in laboratories are mainly based on plasmids or cDNA, which cannot accurately reflect the process of RNA extraction and cDNA synthesis. Therefore, we aimed to develop armored RNA-based standards for p210 and p190 BCR-ABL1FG transcripts' quantification. METHODS: Using overlapping polymerase chain reaction (PCR) technology, we first linked a segment of the p210 or p190 BCR-ABL1FG transcript with four control genes (CGs; ABL1, BCR, GUSB, and B2M) to form p210FG-CG and p190FG-CG. Subsequently, using armored RNA technology, we prepared p210FG-CG- and p190FG-CG-armored RNAs and the p210FG-CG and p190FG-CG standards, the values of which were assigned by digital PCR (dPCR). RESULTS: The p210FG-CG and p190FG-CG standards were stable and homogeneous, and were significantly linear with r2  > 0.98. A field trial including 52 laboratories across China showed that the coefficient of variation (CV%) of BCR-ABL1 values among samples was in the range of 58.6%-129.6% for p210 samples and 73.2%-194.0% for p190 samples when using local standards. By contrast, when using the p210FG-CG and p190FG-CG standards, the CV% of BCR-ABL1 values was decreased to 35.6%-124.9% and 36.6%-170.6% for p210 and p190 samples, respectively. In addition, 33.3% (3/9) of the p210 and p190 samples had CV% values <50.0%, whereas 44.4% (4/9) and 77.8% (7/9) of the samples had lower CV% values when using the p210FG-CG and p190FG-CG standards. CONCLUSION: The overall variability of detection of BCR-ABL1 transcripts decreased significantly when using the p210FG-CG or p190FG-CG standards, especially the p190FG-CG standard.

Assessment of physiological factors for the establishment of serum insulin reference intervals in healthy Chinese Han adults: A community-based large cross-sectional study.

The aim of this study was to investigate physiological factors that affect serum insulin levels and to establish insulin reference intervals for healthy Chinese Han adults. A total of 4401 subjects with normal glucose tolerance (NGT) were screened from 10,027 individuals in an epidemiological study. Based on the exclusion criteria, 2414 apparently healthy adults (healthy) were selected as reference individuals. Serum insulin levels of the reference individuals were measured at fasting, 30 min and 120 min after oral glucose tolerance test (OGTT). Significant correlations were found between serum insulin levels and physiological factors in healthy subjects, including body mass index (BMI), weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. (p < 0.05). No increase or decrease was found in age-dependent insulin levels by ANOVA (p > 0.05). There was also no substantial difference in fasting serum insulin levels between males and females (p > 0.05). However, we detected notable differences in serum insulin levels between males and females at 30 min (p < 0.01), which became more pronounced at 120 min (p < 0.001). According to our data, BMI/gender-related insulin reference intervals were defined by calculating 2.5th and 97.5th percentiles. The insulin reference intervals, determined after assessing the relationship between physiological factors and serum insulin levels in Chinese adults, will provide valuable information for physicians in their interpretation of insulin levels.

K-shell photoabsorption edge of strongly coupled matter driven by laser-converted radiation.

The first observation of the K-shell photoabsorption edge of strongly coupled matter with an ion-ion coupling parameter of about 65 generated by intense x-ray radiation-driven shocks is reported. The soft x-ray radiation generated by laser interaction with a "dog bone" high-Z hohlraum is used to ablate two thick CH layers, which cover a KCl sample, to create symmetrical inward shocks. While the two shocks impact at the central KCl sample, a highly compressed KCl is obtained with a density of 3-5 times solid density and a temperature of about 2-4 eV. The photoabsorption spectra of chlorine near the K-shell edge are measured with a crystal spectrometer using a short x-ray backlighter. The redshift of the K edge up to 11.7 eV and broadening of 15.2 eV are obtained for the maximum compression. A comparison of the measured redshifts and broadenings with dense plasma calculations are made, and it indicates potential improvements in the theoretical description.

Using protein granularity to extract the protein sequence features.

The feature extraction of protein sequences is a challenging problem. It might need a lot of theoretical and practical knowledge from many fields. The difficulty would increase when investigators extract the features solely from protein sequences. In this paper, we present a method of protein granularity. The concepts of protein granularity, granularity order, granularity bound, granularity limit, and granularity increment are given respectively. The protein granularity can dig out the useful information solely from protein sequences. We provide an approach to construct the feature vectors. The feature vectors include the amino acid composition information, the sequence-order information, the same amino acid 'neighbor' information, and the sequence length information. Hence, the feature vectors can better represent protein sequences. Our feature extraction method does obviously consider the protein sequence length effects. An experiment of the protein structure class prediction was carried out. The prediction achieved 96.6% overall accuracy, and the success rate for each subset is all-α 92.3%, all-ß 100%, α/ß 100%, α+ß 93.5%, respectively. The last three success rates for subsets are equal to the best success rates in the published literatures. The overall accuracy of PG-SVM prediction is the second best result only having one protein prediction error difference with the first best result. The theoretical and experimental results demonstrate the application of protein granularity succeeds in the feature extraction of protein sequences.

Evaluation of serum creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate in a Chinese population.

OBJECTIVE: This study aimed to evaluate the applicability of a selection of glomerular filtration rate (GFR) estimating equations based on serum creatinine (SCr) and serum cystatin C in a Chinese population. MATERIAL AND METHODS: Estimated GFR values from 10 equations were compared with reference GFR (rGFR) from the (99m)Tc-DTPA renal dynamic imaging method. The study enrolled 569 Chinese participants (41.5% women, 53.5 ± 16.9 years, range 19-92 years), with mean rGFR 74.80 ± 26.10 (range 9.8-146.8 ml/min/1.73 m(2)). RESULTS: Bland-Altman analysis illustrated that the 95% agreement limits of all the equations surpassed the acceptable tolerance (<60 ml/min/1.73 m(2)), of which the MacIsaac equation was the closest one, reaching 71.7 ml/min/1.73 m(2). Linear regression analysis also demonstrated a consistent result. When assessed in all participants, the accuracy of the six equations reached and exceeded the acceptable level (≥70%), of which the Shanghai and MacIsaac equations gained more accuracy than others. When compared in subgroups, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), MacIsaac and Cockcroft-Gault (CG) equations were optimal for rGFR stages ≥ 90 ml/min/1.73 m(2), 30-89 ml/min/1.73 m(2) and < 30 ml/min/1.73 m(2), respectively. CONCLUSION: The results demonstrated that further improvement is needed for the selected 10 equations. Not all the cystatin C equations were superior to SCr equations. They have their own applicability at various GFR levels. At present, the CKD-EPI, MacIsaac and CG equations may be applied to evaluate GFR in normal, mild to moderate and severe kidney function, respectively.

18F-FDG PET/CT and PET for evaluation of pathological response to neoadjuvant chemotherapy in breast cancer: a meta-analysis.

BACKGROUND: Neoadjuvant chemotherapy is increasingly the treatment for patients with inoperable breast cancer. Considering the side-effects of chemotherapy, there is a need for early evaluating response to neoadjuvant chemotherapy. PURPOSE: To determinate the diagnostic performance of 18F-fluorodeoxyglucose position emission tomography/computed tomography (FDG PET/CT) and FDG PET for evaluating response to neoadjuvant chemotherapy in patients with breast cancer. MATERIAL AND METHODS: "PubMed" (MEDLINE included) database, EMBASE, and Cochrane Database of Systematic Reviews were searched for relevant articles. We assessed the methodological quality of included study with Quality Assessment of Diagnosis Accuracy Studies (QUADAS) score tool, and used "Meta-DiSc" statistic software to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver-operating characteristic (SROC) curve. RESULTS: Seventeen studies (a total of 781 subjects) met the inclusion criteria. The pooled sensitivity was 0.840 (95% confidence interval [CI] 0.796-0.878). The pooled specificity was 0.713 (95% CI 0.667-0.756). For FDG PET/CT (10 studies included), the pooled sensitivity was 0.847 (95% CI 0.793-0.892), the pooled specificity was 0.661 (95% CI 0.598-0.720). The pooled likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were 2.835 (95% CI 1.640-4.900), 0.221 (95% CI 0.160-0.305), and 17.628 (95% CI 7.431-41.818). The area under the SROC curve (AUC) was 0.8934. For FDG PET (7 studies included), the pooled sensitivity and specificity were 0.826 (95% CI 0.741-0.892) and 0.789 (95% CI 0.719-0.849). The pooled LR + , LR-, and DOR were 3.601 (95% CI 2.601-4.986), 0.242 (95% CI 0.157-0.374), and 13.641 (95% CI 7.433-25.030). The AUC was 0.8764. CONCLUSION: Our results indicate that FDG PET/CT and PET have reasonable sensitivity in evaluating response to neoadjuvant chemotherapy in breast cancer; however, the specificity is relative low. The combination of other imaging methods with FDG PET/CT or PET is recommended.

Complement factor H deficiency accelerates development of lupus nephritis.

Complement factor H (CfH) is a key regulator of the alternative pathway, and its presence on mouse platelets and podocytes allows the processing of immune complexes. Because of the role of immune complexes in the pathophysiology of lupus nephritis, we studied the role of CfH in the development of nephritis in MRL-lpr mice, an animal model of lupus. At 12 weeks, CfH-deficient MRL-lpr mice had significantly more albuminuria and higher BUN levels than MRL-lpr controls. Cfh-deficient MRL-lpr mice also experienced earlier mortality: at 14 weeks, 6 of 9 CfH-deficient MRL-lpr mice had died of renal failure, whereas all 11 littermate CfH-sufficient MRL-lpr mice were alive (P ≤ 0.001). Histologically, CfH-deficient MRL-lpr mice developed severe diffuse lupus nephritis by 12 weeks (glomerulonephritis scores of 2.6 ± 0.4 versus 0.4 ± 0.2 in littermate controls, P = 0.001). Similar to other CfH-deficient mouse models on nonautoimmune backgrounds, immunofluorescence staining showed extensive linear C3 staining along glomerular capillary walls. IgG was present in the mesangium and peripheral capillary walls along with excessive infiltration of macrophages and neutrophils. Ultrastructurally, there were subendothelial and subepithelial immune deposits and extensive podocyte foot process effacement. In summary, the loss of CfH accelerates the development of lupus nephritis and recapitulates the functional and structural features of the human disease. This illustrates the critical role of complement regulation and metabolism of immune complexes in the pathogenesis of lupus nephritis.

Overlapping syndrome of recurrent anti-N-methyl-D-aspartate receptor encephalitis and anti-myelin oligodendrocyte glycoprotein demyelinating diseases: A case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (NMDARe) is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease, whereas it has been relatively rare. We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease. CASE SUMMARY: A 29-year-old man was initially admitted with headache, fever, intermittent abnormal behavior, decreased intelligence, limb twitching and loss of consciousness on July 16, 2018. On admission, examination reported no abnormality. During his presentation, he experienced aggravated symptoms, and the re-examination of cranial magnetic resonance imaging (MRI) indicated punctate abnormal signals in the left parietal lobe. External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody (Ab) (-), cerebrospinal fluid NMDAR-Ab (+) 1:10 and Epstein-Barr virus capsid antigen antibody IgG (+). Due to the imaging findings, anti-NMDARe was our primary consideration. The patient was treated with methylprednisolone and gamma globulin pulse therapy, mannitol injection dehydration to reduce intracranial pressure, sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms. The patient was admitted to the hospital for the second time for "abnormal mental behavior and increased limb movements" on December 14, 2018. Re-examination of electroencephalography and cranial MRI showed no abnormality. The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive. Considering comprehensive recurrent anti-NMDARe, the patient was treated with propylene-hormone pulse combined with immunosuppressive agents (mycophenolate mofetil), and the symptoms were relieved. The patient was admitted for "hoarseness and double vision" for the third time on August 23, 2019. Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe, and synoptophore examination indicated concomitant esotropia. The patient's visual acuity further decreased, and the re-examination of cranial MRI + enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata, left pons arm, left cerebellum and right midbrain, thalamus. The patient was diagnosed with an accompanying demyelinating disease. Serum anti-myelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive. The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome. The patient was successfully treated with methylprednisolone, gamma globulin pulse therapy and rituximab treatment. The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion. CONCLUSION: We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.

Distinct roles for C3a and C5a in complement-induced tubulointerstitial injury.

To prevent injury to host tissues, complement activation is regulated by a number of plasma and membrane-associated proteins, most of which limit C3 and C5 activation. An influx of circulating C3 from a syngeneic host into donor kidneys deficient in Crry (a membrane protein that reduces C3 convertase activity) causes spontaneous complement activation, primarily in the tubulointerstitum, leading to renal failure. To determine the roles of the C3a and C5a anaphylatoxins in tubulointerstitial inflammation and fibrosis, kidneys from Crry-/-C3-/- mice were transplanted into hosts lacking the C3a and/or C5a receptor. While unrestricted complement activation in the tubules was not affected by receptor status in the transplant recipient, C3a receptor deficiency in the recipients led to significantly reduced renal leukocyte infiltration and the extent of tubulointerstitial inflammation and fibrosis, all of which led to preserved renal function. The absence of C5a receptors in recipients was not only inconsequential, but the protective effect of C3a receptor deficiency was also eliminated, suggesting distinct roles of C3a and C5a receptor signaling in this model. There was significant infiltration of the tubulointerstitum with 7/4+F4/80+CD11b+ myelomonocytic cells and Thy1.2+ T cells along injured tubules, and interstitial collagen I and III deposition, all of which were C3a receptor dependent. Thus, blockade of C3a receptor signaling is a possible treatment to reduce renal inflammation and preserve renal function associated with complement activation.

Comparison of 18F-FDG PET/CT with bone scintigraphy for detection of bone metastasis: a meta-analysis.

BACKGROUND: The skeleton is one of the favorable sites for the metastasis of almost all human malignant neoplasms. An accurate diagnosis of bone metastasis is crucial for the patient's staging and management. PURPOSE: To investigate and compare diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and bone scintigraphy (BS) for detection of bone metastasis in malignancies using meta-analysis. MATERIAL AND METHODS: PubMed (Medline included) was searched for relevant articles. We assessed the methodological quality with Quality Assessment of Diagnosis Accuracy Studies (QUADAS) score tool, and used statistical software to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver-operating characteristic (SROC) curve. RESULTS: Six studies met inclusion criteria. For 18F-FDG PET/CT, the pooled sensitivity and specificity were 0.934 and 0.975, respectively. The pooled positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnostic odds ratio (DOR) were 34.990, 0.068 and 559.02, respectively. The area under the SROC curve was 0.9854. For BS, the pooled sensitivity, specificity, LR + , LR- and DOR were 0.706 (0.642-0.764), 0.911 (0.896-0.926), 13.982 (2.419-80.817), 0.319 (0.143-0.712), and 60.420 (21.393-170.64), respectively. The area under the SROC curve was 0.9386. CONCLUSION: The results indicate that 18F-FDG PET/CT do have both higher sensitivity and specificity than bone scintigraphy for detecting metastatic bone tumor. However, further research is needed to evaluate the diagnostic performance of 18F-FDG PET/CT and BS in each common malignancy.

Renal FcRn reclaims albumin but facilitates elimination of IgG.

The widely distributed neonatal Fc receptor (FcRn) contributes to maintaining serum levels of albumin and IgG in adults. In the kidney, FcRn is expressed on the podocytes and the brush border of the proximal tubular epithelium. Here, we evaluated the role of renal FcRn in albumin and IgG metabolism. Compared with wild-type controls, FcRn(-/-) mice had a lower t((1/2)) for albumin (28.7 versus 39.9 h) and IgG (29.5 versus 66.1 h). Renal loss of albumin could account for the former, suggested by the progressive development of hypoalbuminemia in wild-type mice transplanted with FcRn-deficient kidneys. Furthermore, serum albumin levels returned to normal in FcRn(-/-) recipients of wild-type kidneys after removing the native FcRn-deficient kidneys. In contrast, renal loss could not account for the enhanced elimination of IgG in FcRn(-/-) mice. These mice had minimal urinary excretion of native and labeled IgG, which increased to wild-type levels in FcRn(-/-) recipients of a single FcRn-sufficient kidney (t((1/2)) of IgG was 21.7 h). Taken together, these data suggest that renal FcRn reclaims albumin, thereby maintaining the serum concentration of albumin, but facilitates the loss of IgG from plasma protein pools.

Standardization of BCR-ABL1 quantification on the international scale in China using locally developed secondary reference panels.

For patients with chronic myeloid leukemia, reverse transcription quantitative polymerase chain reaction is widely used in laboratories to quantify BCR-ABL1 fusion gene transcripts for disease management. Many efforts have been made to standardize the BCR-ABL1 testing assay, including the primary and secondary reference reagents, but the secondary standards have not been developed and used in the standardization program in China. With the use of armored RNA technology, armored RNA of BCR-ABL1 and control genes was manufactured to prepare the secondary reference material anchored to the World Health Organization primary reference calibrators for standardization of BCR-ABL1 testing assays. The secondary reference was sent to 30 laboratories in China for validation. Data from an external quality assessment after the standardization process were collected and analyzed as well. The assigned %BCR-ABL1/ABL1IS values of the four levels of the secondary material panels were 0.0118, 0.1345, 1.3808, and 19.4266, respectively. In validation trials, 70.0% (21/30) of laboratories obtained valid conversion factors for the BCR-ABL1 assay. All valid conversion factors from 11 international scale laboratories were equivalent to their respective previous values. External quality assessment data indicated that the accuracy and precision between laboratories were improved. Moreover, the quantity of the panels is abundant to be used as quality control samples for monitoring the shift of data. In this study, we established a secondary genetic reference panel for BCR-ABL1 quantification. This study will play a role in facilitating the worldwide dissemination of the international scale, especially in promoting the standardization of molecular monitoring in China.

Mesangial cell complement receptor 1-related protein y limits complement-dependent neutrophil accumulation in immune complex glomerulonephritis.

The absence of complement receptor 1 (CR1) related gene/protein y (Crry) leads to embryonic lethality as a result of unrestricted complement activation and concomitant neutrophil infiltration. Here we used Crry(-/-)C3(+/-) mice to investigate the role of Crry in the pathogenesis of immune complex glomerulonephritis (GN). After 3 weeks of immunization with horse spleen apoferritin, six of nine Crry(-/-) C3(+/-) mice and none of the six control C3(+/-) mice developed proliferative GN (P = 0.010). After 5 weeks of immunization, GN scores in Crry(-/-) C3(+/-) mice were 0.67 +/- 0.22 mean +/- standard error of the mean (SEM), compared with 0.32 +/- 0.16 in C3(+/-) mice. Glomerular hypercellularity was attributable to neutrophil infiltration in mice with GN (1.7 +/- 0.3/glomerulus) compared with those without GN (0.4 +/- 0.1/glomerulus) (P = 0.001). Absent staining for alpha-smooth muscle actin and proliferating cell nuclear antigen suggested that mesangial cell proliferation did not play a significant role in this model. Serum C3 levels in Crry(-/-) C3(+/-) mice were approximately 20% and 30% those of wild-type mice and C3(+/-) mice, respectively. To determine whether this acquired hypocomplementaemia was relevant to this GN model system, Crry(-/-) C3(+/-) mouse kidneys were transplanted into wild-type mice followed by immunization with apoferritin for 1 or 2 weeks. Surprisingly, none of the Crry(-/-) C3(+/-) mouse kidneys developed GN at these early time-points, indicating that increasing circulating C3 levels several-fold did not increase susceptibility to GN. Renal expression of decay-accelerating factor was not different among any of the groups studied. Thus, our data indicate that mesangial cell Crry limits complement activation and subsequent neutrophil recruitment in the setting of local immune complex deposition.

External quality assessment of p210 BCR-ABL1 transcript quantification by RT-qPCR: Findings and recommendations.

INTRODUCTION: External quality assessment (EQA) is an essential tool for quality assurance of analytical testing processes of p210 BCR-ABL1 transcripts by RT-qPCR. As an EQA provider, the National Center for Clinical Laboratories organized an EQA scheme of p210 BCR-ABL1 testing in China for the first time to identify existing problems and ensure the reliability of p210 BCR-ABL1 testing. METHODS: Using armored RNA technology, we first constructed pACYC-MS2-p210 and CG recombinant plasmids and expressed p210 and CG armored RNAs, with packaging segments of p210 BCR-ABL1 fusion gene (FG) and four common control gene (CG) transcripts. Using these armored RNAs, we prepared lyophilized p210 quality control (QC) sample panels and evaluated detection performance of participating laboratories in China. RESULTS: Of the 66 participating laboratories, great variation was found with coefficient of variation (CV%) of raw p210 BCR-ABL1 results basically ranging from 60.0% to 100.0%. In 24 International Scale (IS) laboratories, the CV% of results decreased from 82.4% to 61.6%, and the percentage of laboratories within 2-, 3-, and 5-fold of the median values increased from 78.2%, 87.0%, and 92.1% to 80.1%, 89.4%, and 97.2%, respectively, after conversion with a laboratory-specific conversion factor (CF); however, poorly converted results were also observed in laboratories resulting from changed components of RT-qPCR procedures. False-negative and false-positive results were also found in the EQA. CONCLUSIONS: Various problems were found for p210 BCR-ABL1 detection in the EQA. By solving the existing problems, the performance of p210 BCR-ABL1 detection can be improved, ensuring robust laboratory diagnostic capacities in China.

Evaluation of frailty status among older people living in urban communities by Edmonton Frail Scale in Wuhu, China: a cross-sectional study.

BACKGROUND: Few studies have explored the factors that are associated with frailty among older people. OBJECTIVE: To investigate the frailty status and examine the sociodemographic factors that are associated with of older peoples' frailty status in China. DESIGN: Cross-sectional study. METHODS: We used convenience sampling to recruit the participants (aged 60 and above) from four communities in an urban area of Wuhu, Anhui, China. Participants completed a questionnaire which included the Edmonton Frail Scale (EFS) and sociodemographic factorsWe used convenience sampling to recruit the participants (aged 60 and above) from four communities in an urban area of Wuhu, Anhui, China. Participants completed a questionnaire which included the Edmonton Frail Scale (EFS) and sociodemographic factors. RESULTS: Of 306 participants, the percentage of participants with a robust score (0-4) on the EFS was 71.9%, 14.1% had an apparently vulnerable score (5-6), and 14.0% had a frail score (7-17). Age, chronic disease status and marital status were significantly associated with frailty. CONCLUSIONS: There are a high percentage of frail older Chinese adults in the urban area. The present study findings could provide better understanding of the factors associated with frailty status of this population.

Complement in lupus nephritis: the good, the bad, and the unknown.

The complement system consists of 3 pathways and more than 30 proteins, including those with biological activity that directly or indirectly mediate the effects of this system, plus a set of regulatory proteins necessary to prevent injudicious complement activation on host tissue. The role for complement in the pathogenesis of systemic lupus erythematosus (SLE) is paradoxic. On one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classic pathway components are associated with an increased risk for SLE. On the other hand, immune complex-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathologic features that are logical consequences of complement activation. By using accurate mouse models of SLE, we have gained remarkable insights into pathogenic features likely relevant to the human disease, and the ability to test potential therapies, some of which have made it to standard clinical use. Studies in genetically altered mice and using recombinant protein inhibitors of complement have confirmed what was believed but unproven-early complement proteins C1q and C4 are protective whereas complement activation later in the pathways is proinflammatory and deleterious. Two complement inhibitors, soluble complement receptor 1 (TP10, Avant Immunotherapeutics, Needham, MA) and a monoclonal anti-C5 antibody (Eculizumab, Alexion Pharmaceuticals, Inc., Cheshire, CT) have been shown to inhibit complement safely and now are being investigated in a variety of clinical conditions. Although these and others earlier in their clinical development hold promise to be used therapeutically in lupus nephritis, this optimism must be tempered by the fact that the clinical trials to prove this remain fraught with obstacles.

Effects of Buyang Huanwu Decoction on neurite outgrowth and differentiation of neuroepithelial stem cells.

To determine the effects of Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine, on neurite outgrowth and differentiation of neuroepithelial stem cells (NEPs), NEPs were isolated from embryonic neural tube and cultured in medium with rat serum containing BYHWD, which was prepared from rats administrated orally with BYHWD. The average neurite length of NEPs grew significantly longer in rat serum containing BYHWD than in control serum without BYHWD. More neurofilament (NF) positive cells and glial fibrillary acidic protein (GFAP) positive cells were detected in NEPs cultured in the presence of BYHWD. Besides, when cultured NEPs were loaded with Fluo-3-AM, the fluorescence intensity obtained from NEPs cultured in serum with BYHWD was significantly lower than that from NEPs cultured in control serum without BYHWD. Our results indicate that BYHWD could exert a promotion effect on neurite outgrowth and differentiation of NEPs.

Preparation of MS2-based nanoparticles as control and standard materials for the molecular detection of dengue virus serotypes.

To quantify dengue virus (DENV) and evaluate the performance of clinical laboratories using quantitative real-time polymerase chain reaction (qRT-PCR) assays, we constructed high-efficiency expression systems to produce DENV-1 to 4 nanoparticles and assessed their suitability as standard and control materials in 20 laboratories across China. Targeted gene sequences of DENV-1 to 4 were synthesized and inserted into pACYC-Duet 1-MS2 recombinant plasmids to generate corresponding nanoparticle expression systems. After collection, verification, and quantification by digital PCR (dPCR), DENV-1 to 4 nanoparticles were prepared as control and standard materials. Five positive and three negative samples of each DENV serotype in every panel were used for assessing the performance of the participating laboratories across China, as well as standard materials for the quantitative detection of DENV using qRT-PCR assays. The accuracy, sensitivity, and specificity of qRT-PCR used by the 20 evaluated laboratories were 89.6 (569/635), 85.1 (336/395), and 97.1% (233/240), respectively. Overall, sixteen (80.0%) laboratories were qualified in detecting DENV, among which five (25.0%) were designated as "competent", eleven (55.0%) were defined as "acceptable", and four (20%) were considered to be "improvable". The results generated from the DENV standard samples were significantly positively correlated with those generated by dPCR (r2=0.8698, P<0.001). In summary, DENV nanoparticles could potentially be used as controls for improving the performance of laboratories and as standards for the quantitative detection of DENV.