Pyroptosis inhibitors MCC950 and VX-765 mitigate myocardial injury by alleviating oxidative stress, inflammation, and apoptosis in acute myocardial hypoxia.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease with high morbidity and mortality rates worldwide. Pyroptosis is an inflammatory form of programmed cell death that has been linked to various pathological conditions. However, its exact contribution to the onset and progression of heart injury in AMI has not yet fully elucidated. Herein, we established mouse AMI model by ligating the left anterior descending artery and performed transcriptome analysis during the early phase of AMI. Mouse HL-1 and human AC-16 cardiomyocytes were subjected to hypoxia to simulate ischemic injury in vitro. Our results revealed a significant activation of the inflammatory response at 3 h post-ligation, as confirmed by RNA sequencing. We identified the occurrence of NLRP3 inflammasome-mediated pyroptosis in the cardiac tissues of human cases with AMI, as well as in mouse models of AMI and hypoxia-induced cardiomyocytes, using immunohistochemistry staining and Western blotting assays. Concurrently, pharmacological inhibition of NLRP3 inflammasome-mediated pyroptosis with MCC950 and VX-765 effectively decreased hypoxia-induced cardiomyocytes injury, while mitigating myocardial oxidative stress, apoptosis and inflammation caused by hypoxia. Moreover, the circulating levels of gasdermin D (GSDMD), the pyroptosis executor, were remarkably elevated in the plasma of mice with early AMI and in the supernatant of hypoxia-exposed cardiomyocytes in a time-dependent manner using ELISA and Western blotting. Furthermore, the change in circulating GSDMD positively correlated with Creatine Kinase-MB (CK-MB) in the plasma of early-stage AMI mouse. In summary, these findings indicated a critical role for NLRP3 inflammasome-mediated pyroptosis in the progression of AMI, the administration of MCC950 and VX-765 may be attractive candidate therapeutic approaches for cardiac injury caused by acute hypoxia or even AMI. Additionally, the circulating GSDMD exhibits potential as a newly diagnostic biomarker for AMI.

Insight study of rare earth elements in PM2.5 during five years in a Chinese inland city: Composition variations, sources, and exposure assessment.

The booming development of rare earth industry and the extensive utilization of its products accompanied by urban development have led to the accelerated accumulation of rare earth elements (REEs) as emerging pollutants in atmospheric environment. In this study, the variation of REEs in PM2.5 with urban (a non-mining city) transformation was investigated through five consecutive years of sample collection. The compositional variability and provenance contribution of REEs in PM2.5 were characterized, and the REEs exposure risks of children and adults via inhalation, ingestion and dermal absorption were also evaluated. The results showed an increase in the total REEs concentration from 46.46 ± 35.16 mg/kg (2017) to 81.22 ± 38.98 mg/kg (2021) over the five-year period, with Ce and La making the largest contribution. The actual increment of industrial and traffic emission source among the three pollution sources was 1.34 ng/m3. Coal combustion source displayed a downward trend. Ingestion was the main exposure pathway for REEs in PM2.5 for both children and adults. Ce contributed the most to the total intake of REEs in PM2.5 among the population, followed by La and Nd. The exposure risks of REEs in PM2.5 in the region were relatively low, but the trend of change was of great concern. It was strongly recommended to strengthen the concern about traffic-related non-exhaust emissions of particulate matter.

Biomarkers Screening and Mechanisms Analysis of the Restraint Stress-Induced Myocardial Injury in Hyperlipidemia ApoE-/- Mice.

OBJECTIVES: To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/- mice. METHODS: The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/- mice. Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers. RESULTS: Proteomic analysis showed that there were 43 significantly up-regulated and 58 significantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group. Among them, GBP2, TAOK3, TFR1 and UCP1 were biomarkers with great diagnostic potential. KEGG pathway enrichment analysis indicated that ferroptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model. The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model. CONCLUSIONS: Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferroptosis. Four potential biomarkers are selected for myocardial injury diagnosis, providing a new direction for sudden cardiac death (SCD) caused by hyperlipidemia combined with the restraint stress.

Facile fabrication of Fe/Zr binary MOFs for arsenic removal in water: High capacity, fast kinetics and good reusability.

A water-stable bimetallic Fe/Zr metal-organic framework [UiO-66(Fe/Zr)] for exceptional decontamination of arsenic in water was fabricated through a facile one-step strategy. The batch adsorption experiments revealed the excellent performances with ultrafast adsorption kinetics due to the synergistic effects of two functional centers and large surface area (498.33 m2/g). The absorption capacity of UiO-66(Fe/Zr) for arsenate [As(V)] and arsenite [As(III)] reached as high as 204.1 mg/g and 101.7 mg/g, respectively. Langmuir model was suitable to describe the adsorption behaviors of arsenic on UiO-66(Fe/Zr). The fast kinetics (adsorption equilibrium in 30 min, 10 mg/L As) and pseudo-second-order model implied the strong chemisorption between arsenic ions and UiO-66(Fe/Zr), which was further confirmed by DFT theoretical calculations. The results of FT-IR, XPS analysis and TCLP test demonstrated that arsenic was immobilized on the surface of UiO-66(Fe/Zr) through Fe/Zr-O-As bonds, and the leaching rates of the adsorbed As(III) and As(V) from the spent adsorbent were only 5.6% and 1.4%, respectively. UiO-66(Fe/Zr) can be regenerated for five cycles without obvious removal efficiency decrease. The original arsenic (1.0 mg/L) in lake and tap water was effectively removed in 2.0 hr [99.0% of As(III) and 99.8% of As(V)]. The bimetallic UiO-66(Fe/Zr) has great potentials in water deep purification of arsenic with fast kinetics and high capacity.

Cytotoxic and antitumor peptides as novel chemotherapeutics.

Covering: up to 2020Treatment resistance and drug-induced refractory malignancies pose significant challenges for current chemotherapy drugs. There have been increasing research efforts aimed at developing novel chemotherapeutics, especially from natural products and related derivatives. Natural cytotoxic peptides, an emerging source of chemotherapeutics, have exhibited the advantage of overcoming drug resistance and displayed broad-spectrum antitumor activities in the clinic. This highlight examines the increasingly popular cytotoxic peptides from isolated natural products. In-depth review of several peptides provides examples for how this novel strategy can lead to the improved anti-tumor effects. The mechanisms and current application of representative natural cytotoxic peptides (NCPs) have also been discussed, with a particular focus on future directions for interdisciplinary research.

Severe, but not mild to moderate, non-alcoholic fatty liver disease associated with increased risk of subclinical coronary atherosclerosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with high risk of cardiovascular disease. The prevalence is increasing to 45-65% in the general population with routine health check-up, and most subjects have the mild degree NAFLD in recent years. Moreover, there are no studies on the association between NAFLD severity and coronary atherosclerosis in the real-world setting by ultrasonography. METHODS: The aim of this study was to determine the relationship between the severity of NAFLD and subclinical coronary atherosclerosis. Overall, 817 subjects meet criteria for NAFLD were enrolled in the retrospective cohort study (155 subjects were excluded). The severity of NAFLD was divided into the normal, mild, moderate and severe degree based on the finding of abdominal ultrasonography. The assessment of coronary atherosclerosis was based on CAC scan/coronary CT angiography finding in terms of CAC score ≧ 100, CAC score ≧ 400, CAD-RADS ≧ 3 and presence of vulnerable plaque(s). RESULTS: A significant linear trend was observed between the severity of NAFLD and subclinical coronary atherosclerosis. Compared with the reference group (including normal, mild, and moderate NAFLD), severe degree NAFLD was the independently associated risk of subclinical coronary atherosclerosis in term of CAC score ≧ 100, CAC score ≧ 400, CAD-RADS ≧ 3 and presence of vulnerable plaque(s) based on binary logistic regression after adjustment for FRS score and body fat percentage. CONCLUSIONS: Severe degree, but not mild to moderate, was associated with high risk of subclinical coronary atherosclerosis, independently of FRS score and body-fat percentage.

Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors.

Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H+,K+-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs. The gastric acid-suppressive effect of PPIs is affected by both gastric H+,K+-ATPase and CYP2C19 polymorphisms, although gastric H+,K+-ATPase polymorphisms may have larger effects. Ilaprazole and rabeprazole show relatively small differences in the pharmacokinetic and pharmacodynamic properties and clinical efficacy among the different CYP2C19 genotypes. Compared with oral administration, the intravenous infusion of PPIs is less affected by CYP2C19 polymorphism. At the same dose, each enantiomer has less variation among different CYP2C19 genotypes than a racemate mixture.

Natural course of coronary artery calcium progression in Asian population with an initial score of zero.

BACKGROUND: We aimed to investigate the natural course of coronary artery calcium progression in an Asian population with a baseline coronary artery calcium (CAC) score of zero, and to determine subclinical coronary atherosclerosis. METHODS: Four hundred fifty-nine subjects with at least two CAC scans with an initial score of zero were included. CAC progression (+) was defined by the development of any CAC (i.e., CAC > 0) during subsequent CT scans. Clinical characteristics and Framingham risk profiles were also recorded. RESULTS: Among 459 subjects, 106 (23.09%) experienced CAC progression during the average follow-up period of 5.71 ± 2.68 years. Older age, male gender, HDL-C, total cholesterol and higher Framingham risk score were independently associated with CAC progression. Framingham risk score had the better discriminative ability (AUC = 0.660) to predict CAC progression compared to the other parameters with a sensitivity of 75.24% and specificity of 53.95%. For the double zero score with coronary artery atherosclerosis prediction, older age, triglycerides, hypertension, and Framingham risk score were significantly associated with these events. Among these parameters, Framingham risk score may be a relatively acceptable parameter with high negative predictive (NPV = 96.4%) value to rule out double zero score with obstructive coronary artery atherosclerosis scenario with an optimum cut-off value of <16.9 (AUC =0.652, sensitivity of 57.69%; specificity of 68.82%). CONCLUSIONS: A baseline zero CAC score in asymptomatic Chinese population with low to intermediate risk have a low incidence for CAC progression within the 5-years period. For CAC progression prediction, Framingham risk score with the cutoff < 11.1 may help confirm subjects at low risk to improve cardiovascular risk stratification and reclassification in the field of preventive cardiology.

Comparison of the gastric acid inhibition function among lansoprazole, pantoprazole, and their respective stereoisomers in healthy Chinese subjects
.

OBJECTIVE: This study was conducted to evaluate the difference in acid inhibition function among lansoprazole (LPZ), pantoprazole (PPZ), and their respective stereoisomers following single and multiple intravenous doses in healthy Chinese subjects. MATERIALS AND METHODS: The dosage groups were set as follows: 30 mg single and multiple intravenous administrations of LPZ or R-LPZ, 40 mg single and multiple intravenous administrations of PPZ or S-PPZ. Subjects received an intravenous infusion of LPZ, R-LPZ, PPZ, or S-PPZ injection in sterile saline solution (100 mL/h, 60 minutes), respectively. The intragastric pH was sampled every second for 24 hours at baseline and for 24 hours after drug administration. The baseline-adjusted pharmacodynamic (PD) parameters include ΔMean (pH), ΔMedian (pH), ΔTpH≥3 (%), ΔTpH≥4 (%), ΔTpH≥6 (%), and ΔAUECph-tτ1-τ2. The PD parameters were evaluated in different time intervals (0 - 24 hours, 0 - 4 hours and 14 - 24 hours). RESULTS: After a single dose, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ and PPZ was 56.6 ± 19.6, 53.1 ± 23.3, 35.6 ± 24.9 and 26.8 ± 30.2, respectively. The ΔTpH≥6 (%) was 50.7 ± 26.1, 41.4 ± 26.2, 25.4 ± 24.9 and 22.1 ± 27.6, respectively. The ΔAUECph-τ1-τ was 45,564 ± 16,107, 41,798 ± 16,153, 31,914 ± 17,304 and 20,744 ± 21,500, respectively. Statistically significant differences were found with R-LPZ vs. S-PPZ, R-LPZ vs. PPZ, LPZ vs. S-PPZ and LPZ vs. PPZ. The average TpH≥4 of R-LPZ, LPZ, S-PPZ, and PPZ was (47.2 ± 26.1) minutes, (49.6 ± 19.3) minutes, (56.1 ± 23.7) minutes, and (72.1 ± 27.3) minutes, respectively. Statistically significant differences were found with R-LPZ vs. PPZ (p = 0.009) and LPZ vs. PPZ (p = 0.019). After multiple doses, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ, and PPZ was 71.7 ± 20.2, 63.5 ± 19.4, 59.5 ± 17.8 and 64.0 ± 22.4, respectively. The ΔTpH≥6 (%) was 64.0 ± 22.2, 52.0 ± 19.2, 49.6 ± 20.4 and 50.9 ± 23.8, respectively. The ΔAUECph-τ1-τ was 326,149 ± 94,839, 288,565 ± 93,279, 296,189 ± 83,412 and 300,960 ± 108,057, respectively. No statistically significant differences were found in baseline-adjusted PD parameters during all time periods after multiple doses. CONCLUSION: After a single dose, the mean gastric pH inhibition value of R-LPZ was the highest, followed by LPZ, then S-PPZ and PPZ. R-LPZ and LPZ provided significantly better pH control compared with PPZ and S-PPZ in healthy subjects. The onset time of R-LPZ was the fastest and R-LPZ can provide better acid inhibition during sleeping time. After multiple doses, the mean values in all PD parameters of R-LPZ were the highest, the values of LPZ, S-PPZ, and PPZ were similar. However, no significant difference was found in acid inhibition among these four drugs after multiple doses.

Bioavailability/speciation of arsenic in atmospheric PM2.5 and their seasonal variation: A case study in Baoding city, China.

Arsenic (As) can be easily enriched in atmospheric particulate matters (PMs), especially in fine particulate matters (PM2.5). In this study, thirty two PM2.5 samples were collected in four seasons in Baoding, China, where the haze pollution was very serious in recent years. The total contents, species and bioavailability of arsenic in PM2.5 samples were investigated. Species of arsenic in the PM2.5 samples were discriminated as five fractions using a sequential extraction method: non-specifically sorbed fraction (F1), specifically-sorbed fraction (F2), amorphous and poorly-crystalline hydrous oxides of Fe and Al fraction (F3), well-crystallized hydrous oxides of Fe and Al fraction (F4) and residual fraction (F5). Bioavailabilities of arsenic in the PM2.5 samples were evaluated by in vitro tests using both solubility bioavailability research consortium (SBRC) and Gamble's solution extraction methods. The total volume concentrations of As in PM2.5 were significantly higher in winter than the other seasons. However, the highest mass concentration of As was found in spring. Scanning electron microscopy (SEM) characterization indicated that the physical morphology of the particles varied in different seasons. Significant differences of fraction distribution and BFs were found between different seasons. Arsenic in PM2.5 samples mainly presented in F1 with high bioavailability factor (BF), especially for the samples in summer. In vitro tests indicated that arsenic in PM2.5 could be dissolved more easily in gastric phase rather than intestinal and lung phases. There was a significant correlation between species and in vitro tests. Interestingly, a synergy effect was found between F2 and F3. Health risk assessment indicated that arsenic in PM2.5via inhalation exposure for both children and adults could cause adverse effects. Principal component analysis suggested that the arsenic in PM2.5 was from the similar sources between summer and autumn, winter and spring, respectively.

A comparative study on arsenic fractions in indoor/outdoor particulate matters: a case in Baoding, China.

The distribution and bioavailability of arsenic (As) in indoor/outdoor total suspended particulates (TSP), inhalable particulate matters (PM10), and fine particulate matters (PM2.5) in Baoding, China were investigated. The average I/O ratios for TSP, PM10, and PM2.5 were 0.52, 0.66, and 0.96, respectively. There was no significant correlation between indoor/outdoor TSP, PM10, and PM2.5. The indoor/outdoor concentrations of As surpassed the limited value of As. I/O ratios of arsenic in TSP, PM10, and PM2.5 were 0.52, 0.58, and 0.55, respectively. The contents of arsenic in different fractions were mainly affected by the total concentrations of arsenic in particulate matters (PM) rather than the particle sizes for TSP and PM10. Arsenic was mainly in non-specifically sorbed fraction (F1) in both indoor and outdoor PM2.5. The evaluated carcinogenic risk (CR) was within the safe level. The bioavailability of As increased with particle size decreasing for both indoor and outdoor PM. The potential bioavailability of As in outdoor particles was higher than that of indoor particles with the same size, especially PM2.5.

Stereoselective pharmacokinetics of (R)-(+)- and (S)-(-)-rabeprazole in human using chiral LC-MS/MS after administration of rabeprazole sodium enteric-coated tablet.

Rabeprazole is an effective proton pump inhibitor to treat acid-related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC-MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8 minutes on a Chiralpak IC column (4.6 mm × 150 mm, 5 µm). The mobile phase was 10 mM ammonium acetate including 0.2% acetic acid-acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1 â†’ 242.2 and 346.1 â†’ 198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400 ng·mL-1 , the intra-run precisions were below 5.4%, the inter-run precisions were below 9.9%, and the accuracy was between -9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)-(+)- and (S)-(-)-rabeprazole after oral administration of 10-mg rabeprazole sodium enteric-coated tablet in healthy Chinese subjects.

[Application of the Peak Area Ratio of STR Loci to Amelogenin Locus in the Estimation of DNA Degradation].

OBJECTIVE: To explore the change rules of peak area ratio of STR loci to Amelogenin (AMEL) locus (STR/AMEL), a sex-determining gene in DNA degradation, and to evaluate the application of STR/AMEL value in the estimation of DNA degradation degree. METHODS: DNA was extracted from iliopsoas, and the variations of STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) were analyzed after the artificial degradation was made by DNase I, and the changes of these three ratios of the iliopsoas naturally degraded in an outdoor environment were also analyzed. The regression curves were analyzed using the periods of DNA degradation and outside the body as the independent variable (x) and the STR/AMEL value as the dependent variable (y) and three curve equations under two conditions were established. RESULTS: Both under the conditions of artificial and natural degradation, STR/AMEL value had a negative relationship with the degradation time. The relationship between STR/AMEL and degradation time can be well simulated by the cubic function. R2 was over 0.99 under controlled degradation condition and over 0.86 under natural degradation condition. CONCLUSION: The STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) is negatively related with the DNA degradation degree, which follows mathematical regression models strictly, and it might be applied to evaluate the DNA degradation degree.

[Analysis of 59 Anaphylactic Death Cases].

OBJECTIVE: To analyze the cases of anaphylactic death cases and explore the standards of judicial expertise of anaphylactic death for providing evidence for judicial expertise. METHODS: Fifty-nine cases death due to allergic reaction in Shanghai were collected. And details of medical history, clinical manifestation of anaphylactic reaction and postmortem examination findings were reviewed for all cases. RESULTS: In the 59 cases, there were 58 cases died from drug allergy, including 77.6% of them were antibiotics. The rates of treating in standard hospital and illegal clinic were 37.3% and 61.0%, respectively. The allergic symptoms were dyspnea and facial cyanosis. The time from contacting allergens to death ranged from 1 min to 3 d. The concentration of total serum IgE ranged from 50 to 576.92 IU/mL. The results of clinical manifestation and pathological anatomy had obviously changes. CONCLUSION: Based on the exclusion of all other cause of death and synthetically analysis of details of cases, medical history, clinical manifestation and anatomy, the conclusion of anaphylactic death can reached. The details of cases including clinical history, exposure to allergens, and clinical manifestation play an important role in diagnosis of anaphylactic death.

JMJD2A contributes to breast cancer progression through transcriptional repression of the tumor suppressor ARHI.

INTRODUCTION: Breast cancer is a worldwide health problem and the leading cause of cancer death among females. We previously identified Jumonji domain containing 2A (JMJD2A) as a critical mediator of breast cancer proliferation, migration and invasion. We now report that JMJD2A could promote breast cancer progression through transcriptional repression of the tumor suppressor aplasia Ras homolog member I (ARHI). METHODS: Immunohistochemistry was performed to examine protein expressions in 155 cases of breast cancer and 30 non-neoplastic tissues. Spearman correlation analysis was used to analyze the correlation between JMJD2A expression and clinical parameters as well as several tumor regulators in 155 cases of breast cancer. Gene and protein expressions were monitored by quantitative polymerase chain reaction (qPCR) and Western blot. Results from knockdown of JMJD2A, overexpression of JMJD2A, Co-immunoprecipitation (Co-IP) assay, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) elucidated molecular mechanisms of JMJD2A action in breast cancer progression. Furthermore, the effects of ARHI overexpression on JMJD2A-mediated tumor progression were investigated in vitro and in vivo. For in vitro experiments, cell proliferation, wound-healing, migration and invasion were monitored by cell counting, scratch and Boyden Chamber assays. For in vivo experiments, control cells and cells stably expressing JMJD2A alone or together with ARHI were inoculated into mammary fat pads of mice. Tumor volume, tumor weight and metastatic nodules were measured by caliper, electronic balance and nodule counting, respectively. RESULTS: JMJD2A was highly expressed in human breast cancers and positively correlated with tumor progression. Knockdown of JMJD2A increased ARHI expression whereas overexpression of JMJD2A decreased ARHI expression at both protein and mRNA levels. Furthermore, E2Fs and histone deacetylases were involved in the transcriptional repression of ARHI expression by JMJD2A. And the aggressive behavior of JMJD2A in breast cancers could be reversed by re-expression of ARHI in vitro and in vivo. CONCLUSION: We demonstrated a cancer-promoting effect of JMJD2A and defined a novel molecular pathway contributing to JMJD2A-mediated breast cancer progression.

[Expression of EIIIA+ fibronectin in incised wound of rat's skin].

OBJECTIVE: To explore the relationship between the expression of EIIIA+ fibronectin in incised wound of rat's skin and injury time. METHODS: The wounding model was established by cutting the dorsal skin of 48 adult SD rats. The rats were sacrificed at the pre-set injury time as immediately, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, and 8 h. The skin samples were taken at the margin of wound. The expression of the EIIIA? fibronectin was detected by immunohistochemistry and Western blotting and the relationship be- tween its expression and injury time was observed. Results The expression of EIIIA+ fibronectin was not observed immediately. The basal cell of skin began to show positive expression 0.5 h after injury. With the extension of injury time, positive staining became stronger. The value of relative optical density was gradually increased with prolonged injury time by the Western blotting analysis. CONCLUSION: The expression of EIIIA+ fibronectin could be used for estimation of injury time in the early stage of skin injury.

[1H-MRS study on the metabolites of first dorsal interossei].

OBJECTIVE: To estimate the application of prognosis evaluation of ulnar nerve injury by 1H-magnetic resonance spectroscopy (1H-MRS). METHODS: The metabolites of first dorsal interossei (FDI) of two hands from 12 healthy volunteers and 1 volunteer with complete ulnar nerve injury were detected by 1H-MRS and the data were statistically analyzed. RESULTS: For the FDI of healthy adults, the female peaks area of extra-myocellular lipids (EMCL) was higher than the male (P < 0.05); There was no significant difference in Cho, Cr and intra-myocellular lipids (IMCL) between male and female (P > 0.05); There was no significant difference in all the peaks area between the left and right hand (P > 0.05). The EMCL peak of the injury side was higher than that of the healthy side, and the area of FDI was reduced in the volunteer with ulnar nerve injury. CONCLUSION: Noninvasive and quantitative detection of 1H-MRS may be valuable for prognosis evaluation of peripheral nerve injury.

Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China.

Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Expression of JMJD2A in infiltrating duct carcinoma was markedly higher than fibroadenoma, and associated with expression of ARHI, p53 and ER in infiltrating duct carcinoma.

Jumonji Domain Containing 2A (JMJD2A) may be a cancer-associated gene involved in human breast cancer. With a view to investigating expression of JMJD2A in human breast cancer and benign lesion tissues as well as relationship between JMJD2A and tumor related proteins, histological and immunohistochemical analysis, Western blot and quantitative real-time PCR in infiltrating duct carcinoma and fibroadenoma for JMJD2A and immunohistochemical analysis and quantitative real-time PCR in infiltrating duct carcinoma for tumor related proteins (ARHI, p53, ER, PR and CerbB-2) were performed. Histological examination validated the clinical diagnosis. The JMJD2A positive rate of infiltrating duct carcinoma was significantly higher than fibroadenoma by immunohistochemical analysis. The mean optical density of JMJD2A in infiltrating duct carcinoma was higher than fibroadenoma by western blot. JMJD2A mRNA level in infiltrating duct carcinoma was higher than fibroadenoma by quantitative real-time PCR. Spearman correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from immunohistochemical results respectively. Pearson correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from quantitative real-time PCR results respectively. Expression of JMJD2A in infiltrating duct carcinoma was higher, and associated with ARHI, p53 and ER. The results may take JMJD2A as a potential diagnostic and therapeutic target in human breast cancer.