[Performance verification and clinical application evaluation of D-dimer assay].

Objective: To evaluate the clinical application performance of a domestic D-dimer assay reagent (ADX D-dimer). Methods: A total of 546 residual sodium citrate anticoagulated plasma samples (530 of which were used for comparability validation and 16 for sample preparation of other validation components) were selected after the completion of clinical testing at Peking Union Medical College Hospital from Jun 2022 to May 2023. According to the American Clinical Laboratory Standards Institute (CLSI) guidelines, national health industry standards and relevant references, the performance of ADX D-dimer used in Sysmex CS 5100 fully automated coagulation analyzer which included accuracy, precision, linear range, carryover rate, interference resistance capability and reference interval were validated and the agreement compared with two mainstream imported detection reagents (reagent A: Vidas D-dimer reagent; reagent B: Innovance D-dimer detection reagent) was evaluated. The clinical diagnostic efficacy of the ADX D-dimer was evaluated using the ELISA D-dimer (reagent A) test results as criteria. Results: The linear correlation coefficient of the 6-point calibrated absorbance and target value was 0.998, the bias of accuracy met the requirements (-2.8%-8.4%), and the coefficient of variation (CV) of within-run and between-day precision of the two levels were 1.0%-2.7% and 2.7%-4.1%, respectively, which were less than the requirements of the manufacturer's statement and the national health industry standard. The linear range within 0.33-9.69 mg/L FEU was verified and the carryover rate was 0. There was no significant interference with the assay results at bilirubin F≤0.22 g/L, bilirubin C≤0.22 g/L, hemoglobin≤5.5 g/L and celiac≤2 800 FTU. The manufacturer's reference interval≤0.5 mg/L FEU was verified suitable for this laboratory. For 358 samples without suspicious heterophilic antibody whose D-dimer levels range from 0.06 to143.63 mg/L FEU, the correlation between ADX D-dimer and another two assay was good, with r values being 0.968 and 0.975, respectively, the percentage of deviation and relative deviation beyond the 95% confidence interval was 3.4%-4.5% and 5.3%-7.0%. The correlation between ADX D-dimer and ELISA D-dimer was better than that of reagent B in the concentration range of 0.06-1.00 mg/L FEU (r=0.858, 0.134). For 172 samples with heterophilic antibody, the correlation between ADX D-dimer and ELISA D-dimer was still good(r=0.827), with the percentage of deviation and relative deviation being 6.4% (11/172). The diagnostic efficacy was evaluated using 530 samples, and the sensitivity, specificity, positive predictive value, negative predictive value of ADX D-dimer was 97.4%, 77.6%, 91.9%, 91.9%. The area under the curve was 0.976 (95%CI: 0.964-0.987, P<0.001). Conclusion: The ADX D-dimer reagent has superior assay and diagnostic performance, and can meet the needs of clinical laboratories.

[Intestinal microbiota: a new target for early warning, prognosis prediction, prevention and treatment of colorectal cancer].

As the main composition of the gut microbiota, intestinal microbiota directly or indirectly regulate epigenetic modifications, a variety of metabolisms, mucosal and even systemic immune functions of the host, and exert a great influence on the biological behavior of colorectal cancer. Although the detailed mechanism of some enterobacteria involved in the progression of colorectal cancer remains unclear, they are possible markers for early warning and prognostic prediction of colorectal cancer, as well as potential targets for treatment and prevention, which provides us with new hope for the prevention and treatment of colorectal cancer.

[Multimorbidity in elderly patients with acute coronary syndrome: insights from BleeMACS registry].

Objective: To assess the prevalence, pattern and outcome of multimorbidity in elderly patients with acute coronary syndrome (ACS). Methods: Secondary analysis was performed based on the data from the BleeMACS registry, which was conducted between 2003 and 2014. We stratified elderly patients (≥65 years) according to their multimorbidity. Multimorbidity was defined as two or more chronic diseases in the same individual. Kaplan-Meier methods were used to estimate 1 year event rates for each endpoint, and comparisons between the study groups were performed using the log-rank test. The primary endpoint was net adverse clinical events (NACE), which is a composite of all-cause mortality, myocardial infarction, or bleeding. Results: Of 7 120 evaluable patients, 6 391 (89.8%) were with morbidity (1 594 with 1, 2 156 with 2, and 2 641 with ≥3 morbidity). Patients with morbidity were older, percent of female sex and non-ST-elevation acute coronary syndromes and implantation rate with drug-eluting stents and blood creatine level were higher compared to patients without morbidity. Compared with the patients without morbidity, the proportion of participants with oral anticoagulant increased in proportion to increased number of morbidities (5.8% vs. 6.4% with 1 morbidity, 7.3% with 2 morbidities, 9.0% with ≥3 morbidities, P trend<0.01) and the proportion of participants with clopidogrel prescription decreased in proportion to increased number of morbidity (91.9% vs. 89.7% with 1 morbidity, 87.9% with 2 morbidities, 88.6% with ≥3 morbidities, P trend = 0.01). During 1 year follow-up, compared with those with no morbidity, the hazard ratio (HR) and 95% confidence interval (CI) of risk of NACE for those with 1, 2, and ≥ 3 morbidities was 1.18 (0.86-1.64), 1.49 (1.10-2.02), and 2.74 (2.06-3.66), respectively (P < 0.01). Multimorbidity was not associated with an increased risk of bleeding of various organs (P>0.05). Conclusion: Multimorbidity is common in elderly patients with ACS. These patients might benefit from coordinated and integrated multimorbidity management by multidisciplinary teams.

A new Cosmocercoides species (Ascaridida: Cosmocercidae), C. wuyiensis n. sp., from the Asiatic frog Amolops wuyiensis (Amphibia: Anura).

We identified and characterized a new cosmocercid nematode species, Cosmocercoides wuyiensis n. sp., through microscopic examination and sequencing of the partial small ribosomal RNA gene (18S rDNA), internal transcribed spacer (ITS) and mitochondrial cytochrome c oxidase subunit 1 (COI) genes. The new species was isolated from the intestine of the Asiatic frog Amolops wuyiensis Liu and Hu, 1975 captured from four localities of the Anhui province in south-east China. Among the 25 recorded species of the Cosmocercoides genus, the morphology of C. wuyiensis n. sp. is closest to that of C. kiliwai and C. malayensis, which were isolated from various Mexican frog and Malaysian lizard species, respectively. However, C. wuyiensis n. sp. displayed several distinguishing features, such as small size of the male body, two spicules of unequal lengths in the male, small gubernaculum, pre-, ad- and post-cloacal caudal rosette papillae in the ratio of 18-24:2:6 and simple papillae in the ratio of 14:multiple:4, circle and number of punctation in each rosette at 1:11-16, sharply conical tail-end and the presence of lateral alae and somatic papillae in both sexes. BLAST and the phylogenetic analyses of the 18S rDNA and ITS sequences indicated that C. wuyiensis n. sp. belonged to the genus Cosmocercoides, while that of the COI gene sequence of C. wuyiensis n. sp. showed 16.36% nucleotide divergence with C. pulcher and 47.99% nucleotide divergence with C. qingtianensis. The morphological and molecular characterization of C. wuyiensis n. sp. provides new taxonomic data for this genus.

[Characteristics analysis and control countermeasures of acute hydrogen sulfide poisoning in fishing boats in a city from 2009 to 2018].

Objective: To conduct a characteristic analysis of the case of acute hydrogen sulfide poisoning in fishing boats for nearly ten years in a city, and to research on prevention and control measures, so as to provide scientific basis for formulating prevention strategies. Methods: In July 2018, collecting the data of acute hydrogen sulfide poisoning in fishing boats recorded by the Oceanic and Fishery Department & Health Sector from January 1, 2009 to June 30, 2018, the accident characteristics of acute hydrogen sulfide poisoning in fishing boats was analyzed, and compared the differences of hydrogen sulfide poisoning under different classification statistics. Results: In the past ten years, there were 14 acute poisonings in the city, 34 people were poisoned and 12 deaths (the case fatality rate was 35.3%) . According to the types of fishing vessels, the majority number of acute hydrogen sulfide poisoning incidents, poisoned persons and deaths occurred on fishing boats, accounted for 71.4% (10/14) , 76.5% (26/34) and 75.0% (9/12) respectively. From the location of the accident, 85.7% (12/14) of the acute hydrogen sulfide poisoning incidents occurred outside the fishing port. Fisher's exact test showed that the case fatality rate in within the fishing port was higher than that outside the fishing port (P=0.008) . From the cause of direct poisoning, the first three reasons were enter the fish room to rescue, enter the fish room to move fresh catch, to clean the fish room. The poisoning showed seasonal changes, Fisher's exact test showed that the fatality rate in summer was significantly higher than that in spring (P=0.044) , but there was no statistical significance in other seasons (P>0.05) . Conclusion: The acute hydrogen sulfide poisoning of fishing boats in this city has a high case fatality rate, frequent collective poisoning, and showed seasonal changes. Blind rescue, incomplete facilities, and inadequate system are important factors leading to poisoning, so daily measures and rescue measures should be strengthened to reduce the occurrence of poisoning and casualties.

Role of JMJD2B in colon cancer cell survival under glucose-deprived conditions and the underlying mechanisms.

Metabolic stress is a common phenomenon in solid tumors. Compensatory mechanisms to overcome metabolic stress (glucose deprivation) are vital to tumor cell survival. The histone demethylase Jumonji domain-containing protein 2B (JMJD2B) is vital for the growth and progression of various cancers. However, the role of JMJD2B during glucose deprivation remains unclear. Our aim was to examine the function of JMJD2B in glucose-deprived colon cancer cells and the involvement of extracellular signal-regulated kinase (ERK) and glucose transporter 1 (GLUT1). Our study demonstrated that JMJD2B expression was upregulated via ERK phosphorylation during glucose deprivation. Further, the cell viability assay showed that the effect of p-ERK on the viability of colon cancer cells was at least partly dependent on JMJD2B expression. Glucose deprivation increased interaction between JMJD2B and p-ERK, as demonstrated by the co-immunoprecipitation and fluorescence assays. Glucose deprivation also resulted in phosphorylation of JMJD2B by p-ERK, as shown by the immunoprecipitation assay and western blotting analysis. In addition, the phosphorylation of JMJD2B via p-ERK at Thr305, Ser352, Ser566 and Thr1065 contribute to JMJD2B stability. p-ERK stabilizes the JMJD2B protein level by protecting JMJD2B from ubiquitination and proteasome degradation. We found that knockdown of JMJD2B significantly impaired colon cancer cell viability, which is accompanied by a significant reduction in glucose uptake and lactate production. Furthermore, knockdown of JMJD2B after glucose deprivation caused decreased level of GLUT1 through increasing H3K9 tri-methylation levels on its promoter, demonstrated by chromatin immunoprecipitation assay. Moreover, targeting JMJD2B in xenograft tumors also decreased the GLUT1 level. Finally, a positive correlation was observed between p-ERK, JMJD2B and GLUT1 expression in 85 human colon cancer tissue specimens. These results indicated that p-ERK-mediated phosphorylation and stabilization of JMJD2B during glucose deprivation contributes to its role in glucose uptake and cell viability, which may be modulated through epigenetically upregulation of GLUT1.

[Effects of p-phenylenediamine on lung function and health-related quality of life of workers].

Objective: To study the effects p-phenylenediamine (PPD) on lung function and health-related quality of life of occupational exposed workers. Methods: This study was based on data from a company that produce hair dye containing PPD in China. Workers who exposed to PPD were selected as the study group, and workers un-exposed to PPD were selected as the control group. Questionnaires on health-related quality of life of workers using the 36-item Short Form Health Survey (SF-36) . Occupational health examination assessment results were tested in Taizhou Cancer Hospital. The lung function test includes forced vital capacity (FVC) , forced expiratory volume in one second (FEV(1.0)) , and ratio of FEV(1.0) to FVC (FEV(1.0)/FVC) . Results: The difference in systolic blood pressure between the PPD exposed group and the control group was statistically significant (P<0.05) . FVC, FEV(1.0), and FEV(1.0)/FVC of the lung function indexes in the exposed group were lower than those in the control group (P<0.05) . In the health-related quality of life, body pain (P=0.002) , general health (P=0.029) , vitality (P=0.038) , and mental health (P=0.003) were lower in the exposed group than in the control group. Conclusion: Occupational exposed to PPD may induce hazard to the workers'lung function and may cause detrimental effect on workers' health-related quality of life.

[Effects of p-Phenylene diamine on liver and kidney functions of occupational exposed workers].

Objective: To study the effect of p-phenylenediamine (PPD) on liver and kidney function in occupational exposed workers. Methods: Workers in a hair dye production enterprise which used p-phenylenediamine as a raw material for production were selected as the main research population. Then we conducted a questionnaire survey on the basic conditions of workers and conducted occupational health checkups on general health status, liver and kidney function. Occupational health examination assessment results were tested in Taizhou Cancer Hospital. All data was built using EpiData 3.1 software, and statistical analysis was performed using software SPSS 20.0. Results: The liver function indicators including direct bilirubin, prealbumin, total protein, and white protein, globulin, aspartate aminotransferase, glutamyl transpeptidase, and total bilirubin in the workers exposed to high concentration of PPD were at high normal values, and these indicators were significantly different from low PPD concentration group (P<0.05) . The serum creatinine and serum uric acid in the renal function index were significantly higher in workers exposed to PPD than in workers exposed to low concentrations and in the control group (P<0.05) . Conclusion: Occupational exposed to PPD may have a hazard to the workers' liver and kidney function. Long-term occupational exposure to PPD may lead to increased cumulative exposure of workers, which may cause potential chronic liver and kidney damage in occupationally exposed populations.

Characterizing Viscoelastic Modulations in Biopolymer Hydrogels by Coherence-Gated Light Scattering.

pH-responsive hydrogels are of great interest for the controlled release of drugs. However, the changes in the structural and mechanical properties of hydrogels during the pH-responsive swelling/contraction process remains largely unknown. In this article, we demonstrate that coherence-gated dynamic light scattering can be used to in situ characterize the structural dynamics of chitosan (CS) hydrogels at different pH values and show that the CS hydrogels undergo viscoelastic modulations during the swelling/contraction/recovery process induced by pH changes. The conditions for the CS hydrogels to undergo these modulations are found by continuously monitoring the nonequilibrium, long-term dynamical process. Our findings are in a close correspondence to the macroscopic observations made at time points where the CS hydrogels are at equilibrium.

Proteomic identification of ERP29 as a key chemoresistant factor activated by the aggregating p53 mutant Arg282Trp.

Mutation of the TP53 gene represents a prevalent genetic alteration in human cancers, and a subset of p53 mutants may form amyloid-like aggregates that contribute to the gain of oncogenic functions (GOFs) and chemoresistance. Here we identify the pathways that may mediate the aggregation-associated GOF by using combined proteomic analysis and genome-wide recruitment profiling. Mass spectrometry revealed activation of unfolded protein response (UPR) pathway and upregulation of endoplasmic reticulum protein 29 (ERp29) in R282WTP53-expressing cells that were exposed to cisplatin stress. Chromatin immunoprecipitation sequencing identified a significant 'CCCASS' binding motif of Arg282Trp, which is present in the promoter region of ERP29 gene. The mutant p53 upregulated ERP29 mRNA and protein expression levels, whereas targeting ERP29 by specific small interfering RNAs suppressed the chemoresistant effect of Arg282Trp. The anti-aggregation peptide ReACp53 significantly decreased ERP29 expression and suppressed the chemoresistant effect. These findings highlight a role of ERP29 in the acquired chemoresistance of cancer cells expressing the aggregating p53 mutant Arg282Trp. Our results also suggest that ERP29-mediated GOF can be targeted by the anti-aggregation peptide ReACp53.

Floral nectar of the obligate outcrossing Canavalia gladiata (Jacq.) DC. (Fabaceae) contains only one predominant protein, a class III acidic chitinase.

Floral nectar can affect the fitness of insect-pollinated plants, through both attraction and manipulation of pollinators. Self-incompatible insect-pollinated plants receive more insect visits than their self-compatible relatives, and the nectar of such species might face increased risk of infestation by pathogens carried by pollinators than self-compatible plants. Proteins in nectar (nectarins) play an important role in protecting the nectar, but little is known regarding nectarins in self-incompatible species. The nectarins from a self-incompatible and insect-pollinated leguminous crop, Canavalia gladiata, were separated using two-dimensional electrophoresis and analysed using mass spectrometry. The predominant nectarin gene was cloned and the gene expression pattern investigated using quantitative real-time PCR. Chitinolytic activity in the nectar was tested with different substrates. The C. gladiata nectar proteome only has one predominant nectarin, an acidic class III chitinase (CaChi3). The full-length CaChi3 gene was cloned, coding for a protein of 298 amino acids with a predicted signal peptide. CaChi3 is very similar to members of the class III chitinase family, whose evolution is dominated by purifying selection. CaChi3 was expressed in both nectary and leaves. CaChi3 has thermostable chitinolytic activity according to glycol-chitin zymography or a fluorogenic substratem but has no lysozyme activity. Chitinase might be a critical protein component in nectar. The extremely simple nectar proteome in C. gladiata disproves the hypothesis that self-incompatible species always have more complex nectar proteomes. Accessibility of nectar might be a significant determinant of the evolutionary pressure to develop nectar defence mechanisms.

In situ characterization of structural dynamics in swelling hydrogels.

Characterizing the structural morphology and the local viscoelastic properties of soft complex systems raises significant challenges. Here we introduce a dynamic light scattering method capable of in situ, continuous monitoring of structural changes in evolving systems such as swelling gels. We show that the inherently non-stationary dynamics of embedded probes can be followed using partially coherent radiation, which effectively isolates only single scattering contributions even during the dramatic changes in the scattering regime. Using a simple and robust experimental setup, we demonstrate the ability to continuously monitor the structural dynamics of chitosan hydrogels formed by the Ag(+) ion-triggered gelation during their long-term swelling process. We demonstrate that both the local viscoelastic properties of the suspending medium and an effective cage size experienced by diffusing probe particles loaded into the hydrogel can be recovered and used to describe the structural dynamics of hydrogels with different levels of cross-linking. This characterization capability is critical for defining and controlling the hydrogel performance in different biomedical applications.