Robust reactive oxygen species modulator hitchhiking yeast microcapsules for colitis alleviation by trilogically intestinal microenvironment renovation.

Ulcerative colitis (UC) is characterized by chronic inflammatory processes of the intestinal tract of unknown origin. Current treatments lack understanding on how to effectively alleviate oxidative stress, relieve inflammation, as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously. In this study, a novel drug delivery system based on a metal polyphenol network (MPN) was constructed via metal coordination between epigallocatechin gallate (EGCG) and Fe3+. Curcumin (Cur), an active polyphenolic compound, with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN. The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical (O2•-) as well as hydroxyl radical (·OH). By hitchhiking yeast microcapsule (YM), Cur-MPN was then encapsulated into YM to obtain CM@YM. Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon. When administered orally, CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS, reducing pro-inflammatory cytokines, and regulating the polarization of macrophages to M1, thus restoring barrier function and maintaining intestinal homeostasis. Importantly, CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids (SCFA) (such as acetic acid, propionic acid, and butyric acid). Collectively, with excellent biocompatibility, our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.

Breaking Physical Barrier of Fibrotic Breast Cancer for Photodynamic Immunotherapy by Remodeling Tumor Extracellular Matrix and Reprogramming Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve the photodynamic immunotherapy for fibrotic BRCA. FPC@S combines a tumor ECM-targeting peptide, a photosensitizer (protoporphyrin IX) and an antifibrotic drug (SIS3). After anchoring to the ECM, FPC@S causes ECM remodeling and BRCA cell death by generating reactive oxygen species (ROS) in situ. Interestingly, the ROS-mediated ECM remodeling can normalize the tumor blood vessel to improve hypoxia and in turn facilitate more ROS production. Besides, upon the acidic tumor microenvironment, FPC@S will release SIS3 for reprograming CAFs to reduce their activity but not kill them, thus inhibiting fibrosis while preventing BRCA metastasis. The natural physical barrier formed by the dense ECM is consequently eliminated in fibrotic BRCA, allowing the drugs and immune cells to penetrate deep into tumors and have better efficacy. Furthermore, FPC@S can stimulate the immune system and effectively suppress primary, distant and metastatic tumors by combining with immune checkpoint blockade therapy. This study provides different insights for the development of fibrotic tumor targeted delivery systems and exploration of synergistic immunotherapeutic mechanisms against aggressive BRCA.

Does air pollution exposure affect semen quality? Evidence from a systematic review and meta-analysis of 93,996 Chinese men.

Background: Air pollution may impair male fertility, but it remains controversial whether air pollution affects semen quality until now. Objectives: We undertake a meta-analysis to explore potential impacts of six pollutants exposure during the entire window (0-90 days prior to ejaculation) and critical windows (0-9, 10-14, and 70-90 days prior to ejaculation) on semen quality. Methods: Seven databases were retrieved for original studies on the effects of six pollutants exposure for 90 days prior to ejaculation on semen quality. The search process does not limit the language and search date. We only included original studies that reported regression coefficients (ß) with 95% confidence intervals (CIs). The ß and 95% CIs were pooled using the DerSimonian-Laird random effect models. Results: PM2.5 exposure was related with decreased total sperm number (10-14 lag days) and total motility (10-14, 70-90, and 0-90 lag days). PM10 exposure was related with reduced total sperm number (70-90 and 0-90 lag days) and total motility (0-90 lag days). NO2 exposure was related with reduced total sperm number (70-90 and 0-90 lag days). SO2 exposure was related with declined total motility (0-9, 10-14, 0-90 lag days) and total sperm number (0-90 lag days). Conclusion: Air pollution affects semen quality making it necessary to limit exposure to air pollution for Chinese men. When implementing protective measures, it is necessary to consider the key period of sperm development.

Does exposure to air pollution during different time windows affect pregnancy outcomes of in vitro fertilization treatment? A systematic review and meta-analysis.

Few researches have examined the impact of air pollution exposure during various time windows on clinical outcomes in women receiving in vitro fertilization (IVF) therapy, and the findings of studies have been conflicting. We investigated the effects of six air pollutants exposure during different time windows (period 1, 85 days before egg retrieval to the beginning of gonadotropin; period 2, the beginning of gonadotropin to egg collection; period 3, egg collection to embryo transfer; period 4, embryo transfer to serum hCG measurement; period 5, serum hCG measurement to transvaginal ultrasonography; period 6, 85 days before egg retrieval to hCG measurement; period 7, 85 days before egg retrieval to transvaginal ultrasonography) on clinical outcomes of IVF therapy. A total of seven databases were searched. NO2 (period 6), SO2 (period 2, 3, and 7), CO (period 1, 2 and 7) exposure were linked to lower likelihoods of clinical pregnancy. PM2.5 (period 1), PM10 (period 1), SO2 (period 1, 2, 3, 4, and 6), NO2 (period 1) were linked to lower likelihoods of biochemical pregnancy. PM2.5 (period 1), SO2 (period 2 and 4) and CO (period 2) were linked to reduced probabilities of live birth. Our results implied that period 1 might be the most sensitive exposure window. Air pollution exposure is linked to reduced probabilities of clinical pregnancy, biochemical pregnancy, and live birth. Therefore, preventive measures to limit air pollution exposure should be started at least three months in advance of IVF therapy to improve pregnancy outcomes.

Newborn screening and genomic analysis of duchenne muscular dystrophy in Henan, China.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. Recent availability in treatment for DMD raised the need of early screening in our center, but newborn screening (NBS) for DMD has not been carried out in Henan Province. OBJECTIVES: To determine an optimal cutoff value through the quantitative determination of the creatine kinase isoform MM (CK-MM) concentration dried blood spot (DBS) to identify male DMD, and to evaluate assess the detection rate and mutation spectrum of DMD in Henan, China. METHODS: The CK-MM level in DBS was measured using with a GSP® neonatal creatine kinase -MM kit from 13,110 male newborns to establish the cut-off value for CK-MM. Multiplex ligation-dependent probe amplification (MLPA) were carried out for infants with elevated CK levels to detect DMD gene deletions/ duplications, NGS and sanger sequencing were then applied to exclude MLPA-negative samples to single-nucleotide variants. Phenotype-genotype correlations were analyzed using REVEL For novel missense mutations. RESULTS: Statistical analysis of CK-MM value of the 13,110 neonates suggested that the cut-off value may be set as 472 ng/mL. 3 cases of DMD were screened among 13,110 newborns, all of whom had CK-MM levels >600 ng/mL. We detected 4 rare variants in DMD gene, including 2 exon deletions (deletion of exon 52 and deletion from exon 3 to exon 7) and 2 point variants (c.9568C>T and c.4030C>T). Two cases were all exon deletions, one case was compound heterozygous variants. CONCLUSIONS: The estimated incidence of male neonatal DMD was 1:4,370 in Henan province. NBS is of great value to the early intervention and treatment of the disease, and is fundamental to support public health decision-making. The experience from this study provided a model that will allow further expansion and facilitate establishment a universal public health screening in Henan hospital systems.

Characterization of viral infections in children with influenza-like-illness during December 2018-January 2019.

Introduction: Respiratory viral infection (RVI) is of very concern after the outbreak of COVID-19, especially in pediatric departments. Learning pathogen spectrum of RVI in children previous the epidemic of COVID-19 could provide another perspective for understanding RVI under current situation and help to prepare for the post COVID-19 infection control. Methods: A nucleic acid sequence-based amplification (NASBA) assay, with 19 pairs of primers targeting various respiratory viruses, was used for multi-pathogen screening of viral infections in children presenting influenza-like illness (ILI) symptoms. Children with ILI at the outpatient department of Beijing Tsinghua Changgung Hospital during the influenza epidemic from 12/2018 to 01/2019 were included. Throat swabs were obtained for both the influenza rapid diagnostic test (IRDT) based on the colloidal gold immunochromatographic assay and the NASBA assay, targeting various respiratory viruses with an integrated chip technology. Results and discussion: Of 519 patients, 430 (82.9%) were positive in the NASBA assay. The predominant viral pathogens were influenza A H1N1 pdm1/2009 (pH1N1) (48.4%) and influenza A (H3N2) (18.1%), followed by human metapneumovirus (hMPV) (8.8%) and respiratory syncytial virus (RSV) (6.1%). Of the 320 cases identified with influenza A by NASBA, only 128 (40.0%) were positive in the IRDT. The IRDT missed pH1N1 significantly more frequently than A (H3N2) (P<0.01). Influenza A pH1N1 and A (H3N2) were the major pathogens in <6 years and 6-15 years old individuals respectively (P<0.05). In summary, influenza viruses were the major pathogens in children with ILI during the 2018-2019 winter influenza epidemic, while hMPV and RSV were non-negligible. The coexistence of multiple pathogen leading to respiratory infections is the normalcy in winter ILI cases.

Increasing serum antibodies against type B influenza virus in 2017-2018 winter in Beijing, China.

Influenza B virus circulates yearly with lower activity than that of influenza A virus in China. During winter 2017 to 2018, a sharp surge of influenza activity dominated by type B/Yamagata lineage virus caused unprecedented medical burden in Beijing. This research aimed to understand the underlying mechanism for this circulation and prepare for epidemics in the future. Sera samples collected from the patients in 2016-2017 and 2017-2018 flu seasons were tested for profiling hemagglutinin inhibition (HI) antibodies against both prevailing Victoria and Yamagata lineages of type B influenza viruses. It showed that the seroprevalence against both lineages of the virus in 2017-2018 winter was higher than that in 2016-2017, while no difference of the seroprevalence was observed between the two viruses. Meanwhile, significant elevated geometric mean titer (GMT) against both lineages of influenza B viruses was found in the specimens collected during 2017-2018 flu season than that from 2016 to 2017, suggesting the viruses might undergo antigenic changes. These results also suggested that lower GMT against both type B variants in 2016-2017 might serve as an immunological niche for the dominating of B/Yamagata virus in China during 2017-2018 winter season. Our findings have implication that there was a significantly elevation of HI antibodies to influenza viruses B in 2017-2018 than in 2016-2017. On the other hand, the low level of HI antibodies to both B/Y and B/V in 2016-2017 could contribute to the severe B/Y epidemic in 2017-2018 to some extent.

Parental Psychological Control and Children's Prosocial Behavior: The Mediating Role of Social Anxiety and the Moderating Role of Socioeconomic Status.

Complementing internalizing and externalizing developmental outcomes of parental psychological control, in this study, we shift the focus to children's prosocial behaviors. Drawing on self-determination theory and problem-behavior theory, this study addresses the relationship between parental psychological control, social anxiety, socioeconomic status (SES), and children's prosocial behavior. The parental psychological control scale, social anxiety scale for children, and prosocial behavior were applied in the study. Participants were 1202 elementary school-age children in China. The present study showed that parental psychological control was negatively associated with prosocial behavior and social anxiety played a partial mediating role between parental psychological control and prosocial behavior. Meanwhile, SES moderated the relationship between parental psychological control and prosocial behavior. The effect of parental psychological control on prosocial behavior was more significant among students with low levels of SES than the higher ones. The findings showed that parenting plays an essential role in the development of children's prosociality.

Identification and Characterization of Jasmonic Acid Biosynthetic Genes in Salvia miltiorrhiza Bunge.

Jasmonic acid (JA) is a vital plant hormone that performs a variety of critical functions for plants. Salvia miltiorrhiza Bunge (S. miltiorrhiza), also known as Danshen, is a renowned traditional Chinese medicinal herb. However, no thorough and systematic analysis of JA biosynthesis genes in S. miltiorrhiza exists. Through genome-wide prediction and molecular cloning, 23 candidate genes related to JA biosynthesis were identified in S. miltiorrhiza. These genes belong to four families that encode lipoxygenase (LOX), allene oxide synthase (AOS), allene oxide cyclase (AOC), and 12-OPDA reductase3 (OPR3). It was discovered that the candidate genes for JA synthesis of S. miltiorrhiza were distinct and conserved, in contrast to related genes in other plants, by evaluating their genetic structures, protein characteristics, and phylogenetic trees. These genes displayed tissue-specific expression patterns concerning to methyl jasmonate (MeJA) and wound tests. Overall, the results of this study provide valuable information for elucidating the JA biosynthesis pathway in S. miltiorrhiza by comprehensive and methodical examination.

Oral Delivery of Pterostilbene by L-Arginine-Mediated "Nano-Bomb" Carrier for the Treatment of Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown aetiology affecting the colon and rectum. Pterostilbene (PS) has been reported as an effective antioxidant and anti-inflammatory agent in preclinical IBD models. However, the therapeutic outcomes of PS are limited by potential side effects associated with the systemic exposure and the modest bioavailability afforded by its oral administration. These issues can be improved with the use of intelligent responsive nanoparticles with the ability of lysosome escape, given their high drug delivery capacity and reducing the side effects. MATERIALS AND METHODS: Herein, the hyaluronic acid (HA)-modified L-arginine CO2 nanoparticles (HA-L-Arg-CO2@NPs) loaded with PS (HA-PS@NPs) are constructed. Under lysosomal pH conditions, HA-PS@NPs liberate CO2 and generate a pH-activated nano-bomb effect to augment the cytosolic delivery of PS. RESULTS: HA-L-Arg-CO2@NPs show great biocompatibility and the excellent ability to target the colon. Using lipopolysaccharide-induced inflammation in vitro, the prominent anti-inflammatory effect of HA-L-Arg-CO2@NPs and HA-PS@NPs is observed. Further, orally administered HA-L-Arg-CO2@NPs and HA-PS@NPs via the colon-targeted chitosan/alginate (CA) hydrogel downregulate pro-inflammatory cytokines and reduce intestinal permeability, yielding significant outcomes in alleviating the symptoms of UC. CONCLUSION: This pH-activated "nano-bomb" carrier with therapeutic effect can be exploited as efficient oral drug carriers for UC treatment.

Effect of somatometric parameters on the prevalence and severity of varicocele: a systematic review and meta-analysis.

BACKGROUND: Published studies have shown contradictory results regarding the relationship between somatometric parameters and varicoceles. We performed a systematic review and meta-analysis to investigate the possible effects of age, height, weight, and body mass index (BMI) on the presence and severity of varicoceles. METHODS: Databases including EMBASE, MEDLINE, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Web of Science, and Google Scholar were systematically searched to identify relevant articles published up to March 2020. Two researchers independently identified eligible articles and extracted data. Cochran's Q statistic and I2 statistics were used to assess heterogeneity. Meta-analysis was performed using StataSE 12.0 software (StataCorp LP, USA). Random-effects models were used to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Publication bias was assessed using Begg's funnel plot and Egger's regression test. RESULTS: The search strategy produced 272 articles, of which 18 articles were eligible according to the inclusion/exclusion criteria. A total of 56,325 patients with varicocele and 1,334,694 patients without varicocele were included in the meta-analysis to evaluate the effect of somatometric parameters on the presence and severity of varicocele. The overall results demonstrated that the presence of varicoceles was significantly associated with height (WMD = 1.41, 95% CI = 1.07 to 1.74, P < 0.001) and inversely correlated with BMI (WMD = - 1.35, 95% CI = -1.67 to - 1.03, P < 0.001) but not with age (WMD = -0.93, 95% CI = -2.19 to 0.33, P = 0.149) or weight (WMD = 0.24, 95% CI = -2.24 to 2.72, P = 0.850). The severity of varicocele was inversely correlated with increased BMI but not with age. CONCLUSION: The presence of varicoceles was significantly associated with height and inversely correlated with BMI.

Organizing pneumonia of COVID-19: Time-dependent evolution and outcome in CT findings.

BACKGROUND: As a pandemic, a most-common pattern resembled organizing pneumonia (OP) has been identified by CT findings in novel coronavirus disease (COVID-19). We aimed to delineate the evolution of CT findings and outcome in OP of COVID-19. MATERIALS AND METHODS: 106 COVID-19 patients with OP based on CT findings were retrospectively included and categorized into non-severe (mild/common) and severe (severe/critical) groups. CT features including lobar distribution, presence of ground glass opacities (GGO), consolidation, linear opacities and total severity CT score were evaluated at three time intervals from symptom-onset to CT scan (day 0-7, day 8-14, day > 14). Discharge or adverse outcome (admission to ICU or death), and pulmonary sequelae (complete absorption or lesion residuals) on CT after discharge were analyzed based on the CT features at different time interval. RESULTS: 79 (74.5%) patients were non-severe and 103 (97.2%) were discharged at median day 25 (range, day 8-50) after symptom-onset. Of 67 patients with revisit CT at 2-4 weeks after discharge, 20 (29.9%) had complete absorption of lesions at median day 38 (range, day 30-53) after symptom-onset. Significant differences between complete absorption and residuals groups were found in percentages of consolidation (1.5% vs. 13.8%, P = 0.010), number of involved lobe > 3 (40.0% vs. 72.5%, P = 0.030), CT score > 4 (20.0% vs. 65.0%, P = 0.010) at day 8-14. CONCLUSION: Most OP cases had good prognosis. Approximately one-third of cases had complete absorption of lesions during 1-2 months after symptom-onset while those with increased frequency of consolidation, number of involved lobe > 3, and CT score > 4 at week 2 after symptom-onset may indicate lesion residuals on CT.

Prebiotics-Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer.

While microbial-based therapy has been considered as an effective strategy for treating diseases such as colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which possess ideal biocompatibility and are extensively used as additives in food and pharmaceutical products, are combined to construct a safe microbiota-modulating material. Through the host-guest chemistry between commercial Clostridium butyricum and chemically modified prebiotic dextran, prebiotics-encapsulated probiotic spores (spores-dex) are prepared. It is found that spores-dex can specifically enrich in colon cancers after oral administration. In the lesion, dextran is fermented by C. butyricum, and thereby produces anti-cancer short-chain fatty acids (SCFAs). Additionally, spores-dex regulate the gut microbiota, augment the abundance of SCFA-producing bacteria (e.g., Eubacterium and Roseburia), and markedly increase the overall richness of microbiota. In subcutaneous and orthotopic tumor models, drug-loaded spores-dex inhibit tumor growth up to 89% and 65%, respectively. Importantly, no obvious adverse effect is found. The work sheds light on the possibility of using a highly safe strategy to regulate gut microbiota, and provides a promising avenue for treating various gastrointestinal diseases.

A Pattern Categorization of CT Findings to Predict Outcome of COVID-19 Pneumonia.

Background: As global healthcare system is overwhelmed by novel coronavirus disease (COVID-19), early identification of risks of adverse outcomes becomes the key to optimize management and improve survival. This study aimed to provide a CT-based pattern categorization to predict outcome of COVID-19 pneumonia. Methods: One hundred and sixty-five patients with COVID-19 (91 men, 4-89 years) underwent chest CT were retrospectively enrolled. CT findings were categorized as Pattern 0 (negative), Pattern 1 (bronchopneumonia pattern), Pattern 2 (organizing pneumonia pattern), Pattern 3 (progressive organizing pneumonia pattern), and Pattern 4 (diffuse alveolar damage pattern). Clinical findings were compared across different categories. Time-dependent progression of CT patterns and correlations with clinical outcomes, i.e." discharge or adverse outcome (admission to ICU, requiring mechanical ventilation, or death), with pulmonary sequelae (complete absorption or residuals) on CT after discharge were analyzed. Results: Of 94 patients with outcome, 81 (86.2%) were discharged, 3 (3.2%) were admitted to ICU, 4 (4.3%) required mechanical ventilation, 6 (6.4%) died. 31 (38.3%) had complete absorption at median day 37 after symptom onset. Significant differences between pattern-categories were found in age, disease severity, comorbidity and laboratory results (all P < 0.05). Remarkable evolution was observed in Pattern 0-2 and Pattern 3-4 within 3 and 2 weeks after symptom-onset, respectively; most of patterns remained thereafter. After controlling for age, CT pattern significantly correlated with adverse outcomes [Pattern 4 vs. Pattern 0-3 [reference]; hazard-ratio [95% CI], 18.90 [1.91-186.60], P = 0.012]. CT pattern [Pattern 3-4 vs. Pattern 0-2 [reference]; 0.26 [0.08-0.88], P = 0.030] and C-reactive protein [>10 vs. ≤ 10 mg/L [reference]; 0.31 [0.13-0.72], P = 0.006] were risk factors associated with pulmonary residuals. Conclusion: CT pattern categorization allied with clinical characteristics within 2 weeks after symptom onset would facilitate early prognostic stratification in COVID-19 pneumonia.

Effects of PVP-coated silver nanoparticles on enzyme activity, bacterial and archaeal community structure and function in a yellow-brown loam soil.

The undesirable effects of silver nanoparticles (AgNPs) on soil environment have caused much concern. The previous studies, however, focused on sandy soil, with little known on others. In present study, the effects of polyvinylpyrrolidone-coated AgNPs (0, 1, 10, and 100 mg kg- 1 soil) on enzyme activities (urease and dehydrogenase), ammonia-oxidizing bacteria (AOB) and archaea (AOA), bacterial and archaeal communities, and microbial function profile in a yellow-brown loam soil were investigated. The significant dose-response inhibitions of AgNPs on enzyme activities were observed, with dehydrogenase more susceptible to AgNPs. Both of bacterial and archaeal amoA genes were reduced by AgNPs above 10 mg kg- 1, with AOB more susceptible to AgNPs than AOA. AgNPs at 100 mg kg- 1 caused reductions on the dominant Nitrosospira and Nitrosomonas, and even disappearance on Nitrosovibrio, while increase on Nitrososphaera significantly. AgNPs also changed bacterial and archaeal community structure. Exposure to AgNPs at 100 mg kg- 1 caused significant increases by 186.79% and 44.89% for Bacteroidetes and Proteobacteria, while decreases by 47.82%, 44.09%, 43.67%, and 80.44% for Actinobacteria, Chloroflexi, Planctomycetes, and Verrucomicrobia, respectively. Moreover, three dominant archaeal phyla (Thaumarchaeota, Euryarchaeota, and Parvarchaeota) were also reduced in the presence of AgNPs, especially Thaumarchaeota with the significant reduction of 13.71%. PICRUSt prediction revealed that AgNPs indeed had the potential to change soil microbial community's functional contributions. It must be cautious on the interference of AgNPs to soil ecological functions in the future.

Enhance the effectiveness of clinical laboratory critical values initiative notification by implementing a closed-loop system: A five-year retrospective observational study.

BACKGROUND: Accurate and timely clinical laboratory critical values notification are crucial steps in supporting effective clinical decision making, thereby improving patient safety. METHODS: A closed-loop laboratory critical value notification system was developed by a multidisciplinary team of clinicians, laboratorians, administrators, and information technology experts. All the laboratory critical values that occurred at Beijing Tsinghua Changgung Hospital (BTCH, Beijing, China) from 2015 to 2019 were analyzed and studied retrospectively. RESULTS: The total number (ratio) of institutional laboratory critical values to all reported items at BTCH from 2015 to 2019 was 38 020/7 706 962 (0.49%). Percentage distribution points of critical value boundaries based on patients' test reports are 0.007% ~ 6.04% for low boundaries and 71.70% ~ 99.99% for high boundaries. After the intervention, the timely notification ratio, notification receipt ratio, and timely notification receipt ratio of critical values of ED, IPD, and total patients had increased, with a significant difference (P < .001). Five quality indicators, such as notification ratio, timely notification ratio, notification receipt ratio, timely notification receipt ratio, and clinician response ratio over a 5-year period, were 100%, 94%, 97%, 92%, and 99%, respectively. CONCLUSIONS: We enhanced the effectiveness of clinical laboratory critical values initiative notification by implementing a closed-loop system and intervening. Clinical critical values and quality indicators should be analyzed and monitored to avoid adversely affecting patient care.

Evaluation of a fluorescent immunochromatography test for fecal calprotectin.

BACKGROUND: Fecal calprotectin (FC) is widely used to discriminate between patients with inflammatory diseases such as inflammatory bowel disease (IBD) and functional diseases such as irritable bowel syndrome (IBS). ELISA is a time-consuming method for the measurement of FC, whereas a fluorescent immunochromatography test can obtain results in around 30 minutes and thus enables a rapid response to clinical decision. METHODS: Two methods, the Proglead® calprotectin (FC Proglead) and the BÜHLMANN fCAL® ELISA (FC BÜHLMANN), were used to quantitatively examine FC in 111 stool samples. The comparison and bias estimation of both assays were assessed using CLSI EP09c protocol. RESULTS: The two methods were highly correlated (rho = .96). Deming regression was employed to calculate the regression equation, with a slope of 1.01 and an intercept of -4.98 µg/g. The estimated median bias (FC Proglead - FC BÜHLMANN) was -4.19 µg/g with the 95% limits of agreement (-55.59 to 47.21 µg/g), and the estimated median percent bias was -8.71% with the 95% limits of agreement (-50.31% to 32.90%). There was 4.50% (5/111) of values outside the 95% limits of agreement. Percent biases at the FC cutoff values of 50 and 200 µg/g between both methods evaluated by Deming regression were 8.96% and 1.49%, respectively. The biases were all less than the acceptable standard (10%). And, 99.10% of FC results were in agreement between both methods (kappa = .99, P < .001). CONCLUSIONS: FC Proglead may be used as a suitable alternative to FC BÜHLMANN for the disease activity assessment for patients with IBD, considering its convenience and shorter turnaround time.

Numerical Analysis and Experimental Study on Fabrication of High Aspect Ratio Tapered Ultrafine Holes by Over-Growth Electroforming Process.

High aspect ratio (HAR) ultrafine tapered holes (diameter ≤5 µm; AR ≥5) are the most important elements for some high-tech perforated metallic products, but they are very difficult to manufacture. Therefore, this paper proposes a nontraditional over-growth electroforming process. The formation mechanism of the HAR ultrafine tapered holes is investigated, and the factors controlling the geometric shape evolution are analyzed numerically. It was found that the geometric shape and dimensions of the holes are highly dependent on the diameter and thickness of the photoresist film patterns, but are hardly affected by the spacing between two neighboring patterns; the achievable diameter for a given hole depth becomes small with the increasing pattern diameter, but it becomes big with the increasing pattern thickness. These correlations can be well interpreted by the established two empirical equations that characterize the relationship between the minimum orifice of the tapered hole and the structural parameters of the photoresist film patterns previously formed on the substrate. Application of the fabricated 1500 tapered holes with 3-µm diameter and 17-AR as the nozzles of the medical precision nebulizer is also examined. The studies show that the over-growth electroforming process is highly applicable in fabricating the perforated metallic plate with HAR ultrafine tapered holes.

Enzyme-Driven Membrane-Targeted Chimeric Peptide for Enhanced Tumor Photodynamic Immunotherapy.

Here, a protein farnesyltransferase (PFTase)-driven plasma membrane (PM)-targeted chimeric peptide, PpIX-C6-PEG8-KKKKKKSKTKC-OMe (PCPK), was designed for PM-targeted photodynamic therapy (PM-PDT) and enhanced immunotherapy via tumor cell PM damage and fast release of damage-associated molecular patterns (DAMPs). The PM targeting ability of PCPK originates from the cellular K-Ras signaling, which occurs exclusively to drive the corresponding proteins to PM by PFTase. With the conjugation of the photosensitizer protoporphyrin IX (PpIX), PCPK could generate cytotoxic reactive oxygen species to deactivate membrane-associated proteins, initiate lipid peroxidation, and destroy PM with an extremely low concentration (1 µM) under light irradiation. The specific PM damage further induced the fast release of DAMPs (high-mobility group box 1 and ATP), resulting in antitumor immune responses stronger than those of conventional cytoplasm-localized PDT. This immune-stimulating PM-PDT strategy also exhibited the inhibition effect for distant metastatic tumors when combined with programmed cell death receptor 1 blockade therapy.

Comparative analysis of calculating sigma metrics by a trueness verification proficiency testing-based approach and an internal quality control data inter-laboratory comparison-based approach.

INTRODUCTION: Two methods were compared for evaluating the sigma metrics of clinical biochemistry tests using two different allowable total error (TEa) specifications. MATERIALS AND METHODS: The imprecision (CV%) and bias (bias%) of 19 clinical biochemistry analytes were calculated using a trueness verification proficiency testing (TPT)-based approach and an internal quality control data inter-laboratory comparison (IQC)-based approach, respectively. Two sources of total allowable error (TEa), the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) and the People's Republic of China Health Industry Standard (WS/T 403-2012), were used to calculate the sigma metrics (σCLIA, σWS/T ). Sigma metrics were calculated to provide a single value for assessing the quality of each test based on a single concentration level. RESULTS: For both approaches, σCLIA  > σWS/T in 18 out of 19 assays. For the TPT-based approach, 16 assays showed σCLIA  > 3, and 12 assays showed σWS/T  > 3. For the IQC-based approach, 19 and 16 assays showed σCLIA  > 3 and σWS/T  > 3, respectively. CONCLUSIONS: Both methods can be used as references for calculating sigma metrics and designing QC schedules in clinical laboratories. Sigma metrics should be evaluated comprehensively by different approaches.