OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Objective:To investigate the value of artificial intelligence (AI)-assisted quantitative measurement in evaluation of the dynamic changes of CT for COVID-19 pneumonia.Methods:The clinical and chest CT dynamic imaging data of 99 patients with confirmed COVID-19 pneumonia who were hospitalized in Wuhan Central Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 15, 2020 to March 10, 2020 were retrospectively analyzed. According to the definitive diagnosis, the 99 patients were classified into common ( n=36), severe ( n=33) and critical ( n=30) type, the CT imaging findings of each type were analyzed, including CT basic signs, total volume of pneumonia lesions and percentage of pneumonia lesions of the total lung volume (volume ratio). AI software was used to quantitatively evaluate the dynamic changes of chest CT images. The quantitative indicators included CT peak time of lesions, total volume of lesions peak, volume ratio of lesions peak, maximum growth rate of total volume and maximum growth rate of volume ratio. Kruskal-Wallis rank sum test was used to compare the difference of quantitative indexes between the 3 types, and χ 2 test or Fisher exact probability test was used to compare the difference of qualitative indexes between the 3 types. Sequence measurement and scatter plots were used to show the evolution trend of the volume ratio of the three types of COVID-19 pneumonia lesions. The ROC curve was used to analyze the value of the volume ratio of pneumonia lesions and its maximum growth rate in predicting the conversion of common pneumonia to severe or critical pneumonia. Results:There were statistically significant differences in age and gender distribution among patients with common, severe and critical COVID-19 ( P<0.05), the age of severe and critical types were significantly higher than that of common type ( P<0.01). Compared with common [2.5 (1.0, 5.0) d] and critical type[2.5 (1.0, 4.0) d], the time from onset to the first chest CT scan of severe type was prolonged [5.0 (2.5, 8.0) d, P<0.01]. There were statistically significant differences in involvement of multiple lung lobes (20 cases, 29 cases, 25 cases, χ2=10.403, P=0.006) in patients with common, severe and critical COVID-19 at the first scan, the incidence of the involvement of multiple lung lobes in severe and critical types was significantly higher than that of common type ( P=0.002). The volume ratios of patients with common, severe and critical COVID-19 at the first scan were statistically significant [1.0% (0.2%, 4.7%), 9.30% (1.63%, 26.83%), 2.10% (0.64%, 8.61%), Z=14.236, P=0.001], and the volume ratio of severe type was significantly higher than that of common type ( P<0.001), there was no statistically significant difference between common type and critical type ( P=0.062). Follow-up CT showed that the pneumonia lesions showed a dynamic transformation of progress and recovery, and it was seen that the coexistence of multiphase lesions. The trend line in the scatter plot of the three types of COVID-19 pneumonia lesions showed that the lesions in the advanced stage developed from less to more. The lesion peak volume ratios of the common, severe and critical types were 9.75% (4.83%, 13.18%), 29.80% (23.99%, 42.36%) and 61.81% (43.73%, 72.82%), respectively, the difference was statistically significant ( Z=74.147, P<0.001). The maximum growth rates of lesion volume ratio were 1.27% (0.50%, 1.81%)/d, 4.39% (3.16%, 5.54%)/d and 6.02% (4.77%, 9.96%)/d, respectively, the difference was statistically significant ( Z=52.453, P<0.001). The peak times of lesions were 12.0 (9.0, 15.0) d, 13.0 (10.0, 16.0) d and 16.5 (12.0, 25.0)d, respectively, the difference was statistically significant ( Z=9.524, P=0.009). Taking the volume ratio of pneumonia lesion 22.60% and the maximum growth rate of the volume ratio 1.875%/d as the boundary value, the sensitivity of diagnosing common type to severe or critical type was 92.10% and 96.83%, and the specificity was 100% and 80.56%, respectively. The area under the curve was 0.987 and 0.925, respectively. Conclusions:The lesions of COVID-19 pneumonia show a similar parabolic change on CT imaging. The use of AI technology to dynamitcally and accurately measure the CT pneumonia lesion volume ratio is helpful to evaluate the severity of the disease and predict the development trend of the disease. Patients with a rapid growth of volume ratio are more likely to become severe or critical type.

Objective To investigate the clinical effects of pars repair by the pedicle screws,laminal hooks and auto iliac bone graft through the Wiltse approach via Quadrant channel for the treatment of the adolescent spodylolysis.Methods From November 2007 to April 2011,pars defects of 11 patients (10 males and 1 female) were repaired with pedicle screws,laminal hooks and auto iliac bone graft via Quadrant channel through the Wiltse approach.The mean age of 11 patients was 17.3 years (range 15-19).Mean course was 9.9 months (range 6-14 months).All patients have bilateral pars defect of L5.There was no poroma across the pars that have been proved by X-ray film and 3-D CT before the operation.There were 4 patients with Ⅰ grade spondylolisthesis.The degeneration of the intervertebral disc assessed by Pfirrmann grade of all patients was no more than Ⅰ grade.Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared before and after operation.The fusion of pars defect was observed by X-ray film and 3-D CT.Results The mean operation time was 85.5±12.3 min (range 70-110 min); intraoperatve blood loss was 80-150 ml (mean 105 ± 19.4 ml).Two patients were lost in follow-up after operation and the others had been followed up for 12 to 24 months (mean 16 months).All patients had significant pain relief and function recovery after operation.Mean postoperative VAS score was 1.5± 1.0 compared with 4.5± 1.0 of preoperation (t=4.603,P=0.002).ODI was decreased from 49.3％± 14.2％ of preoperation to 12.0％±4.9％ of the last follow-up (t=7.344,P=0.000).With the Macnab grades,7 patients are excellent,2 patients are good.3-D CT showed that all pars defect were fused in the last follow-up.Conclusion Pars repair by the pedicle screws,laminal hooks and auto iliac bone graft through the Wiltse approach via Quadrant channel can protect the paravertebral muscle,relief patients from pain,and improve function.

Objective To investigate the clinical characteristics of pulmonary actinomycosis and to improve the understanding of the clinical misdiagnosis of pulmonary actinomycosis. Method Clinical data of 4 pulmonary actinomycosis patients were analized and related literatures were reviewed. Results All the 4 pulmonary actinomy-eosis cases were misdiaguosed as lung cancer. Pulmonary actinomycosis can be correctly diagnosed through lung bi-opsy by CT-guided percutaneous paracentesis,fiberoptic,bronchoscopy,or pathological examination of the resected pulmonary lobe. Conclusions Pulmonary actinomycosis is a rare lung infection caused by fungus,and is liable to be misdiagnosed as peripheral lung cancer. The capacity of distinguishing pulmonary actinomycosis from peripheral lung cancer needs to be improved.

This experiment was designed to study the apoptosis and related mechanism of adherent liver tumor cells (SMMC-7721) and adherent normal liver cells (HL-7702) when they were exposed to the steep pulse generated by the steep pulse apparatus for tumor treatment. The results showed that the steep pulse of 200 V could induce tumor cells apoptosis. The tumor cells presented with their apoptosis when they were exposed to the steep pulse from 200 V to 250 V. Laser scanning confocal microscopy was used to make a real time study of calcium burst when the adherent tumor cells were exposed to the steep pulse. The results showed:On the condition of no extracellular Ca2+, the concentration of Ca2+ in tumor cells exposed to the steep pulse of 150 V did not change; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 200 V decreased; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 250 V decreased more evidently. On the condition of existing extracellular Ca2+, the concentration of Ca2+ in tumor cells exposed to the steep pulse of 150 V did not change; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 200 V decreased little; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 250 V reduced little, too. Maybe the change of calcium burst in the tumor cells is the mechanism of apoptosis when cells are exposed to the steep pulse.
Apoptosis ; radiation effects ; Calcium ; metabolism ; Electricity ; Electromagnetic Fields ; Hepatocytes ; cytology ; pathology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Microscopy, Confocal ; Tumor Cells, Cultured