Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

Plant height is an important component of plant architecture and significantly affects crop breeding practices and yield. We studied DNA variations derived from F5 recombinant inbred lines (RILs) with 96.8% homozygous genotypes. Here, we report DNA variations between the normal and dwarf members of four lines harvested from a single seed parent in an F6 RIL population derived from a cross between Glycine max var. Peking and Glycine soja IT182936. Whole genome sequencing was carried out, and the DNA variations in the whole genome were compared between the normal and dwarf samples. We found a large number of DNA variations in both the dwarf and semi-dwarf lines, with one single nucleotide polymorphism (SNP) per at least 3.68 kb in the dwarf lines and 1 SNP per 11.13 kb of the whole genome. This value is 2.18 times higher than the expected DNA variation in the F6 population. A total of 186 SNPs and 241 SNPs were discovered in the coding regions of the dwarf lines 1282 and 1303, respectively, and we discovered 33 homogeneous nonsynonymous SNPs that occurred at the same loci in each set of dwarf and normal soybean. Of them, five SNPs were in the same positions between lines 1282 and 1303. Our results provide important information for improving our understanding of the genetics of soybean plant height and crop breeding. These polymorphisms could be useful genetic resources for plant breeders, geneticists, and biologists for future molecular biology and breeding projects.

Plant height is an important component of plant architecture and significantly affects crop breeding practices and yield. We studied DNA variations derived from F5 recombinant inbred lines (RILs) with 96.8% homozygous genotypes. Here, we report DNA variations between the normal and dwarf members of four lines harvested from a single seed parent in an F6 RIL population derived from a cross between Glycine max var. Peking and Glycine soja IT182936. Whole genome sequencing was carried out, and the DNA variations in the whole genome were compared between the normal and dwarf samples. We found a large number of DNA variations in both the dwarf and semi-dwarf lines, with one single nucleotide polymorphism (SNP) per at least 3.68 kb in the dwarf lines and 1 SNP per 11.13 kb of the whole genome. This value is 2.18 times higher than the expected DNA variation in the F6 population. A total of 186 SNPs and 241 SNPs were discovered in the coding regions of the dwarf lines 1282 and 1303, respectively, and we discovered 33 homogeneous nonsynonymous SNPs that occurred at the same loci in each set of dwarf and normal soybean. Of them, five SNPs were in the same positions between lines 1282 and 1303. Our results provide important information for improving our understanding of the genetics of soybean plant height and crop breeding. These polymorphisms could be useful genetic resources for plant breeders, geneticists, and biologists for future molecular biology and breeding projects.

Objective:To evaluate the feasibility of making individualized scanning and contrast injection protocol based on body mass index (BMI) and body weight during dynamic myocardial computed perfusion (CTP) imaging in order to get high-quality images while drastically reducing radiation dose.Methods:A total of 128 patients with coronary heart disease diagnosed by coronary CTA (CCTA) performed CTP from June, 2019 to March, 2020 were prospectively enrolled. Patients were divided into six groups: group 1, BMI<24 kg/m 2, ≤60 kg, 70 kV; group 2,BMI<24 kg/m 2, 61≤kg≤70, 70 kV; group 3, BMI 24-28 kg/m 2, 61≤kg≤70, 80 kV; group 4, BMI 24-28 kg/m 2, 71≤kg≤80, 80 kV; group 5, BMI 24-28 kg/m 2,>80 kg, 80 kV;group 6, BMI>28 kg/m 2,>80 kg, 100 kV. 200 mA was fixed for all patients. Contrast agent with iodine containing 370 mg/ml was used in all patients. The iodine delivery rates (IDR) for each group was 0.8, 1.0, 1.2, 1.4, 1.6, 2.0 g/s, respectively. The attenuation and noise of left ventricle (LV) and septal myocardial were measured to calculate signal to noise ratio (SNR) and contrast to noise ratio (CNR) of the images in each group. The Shapiro-Wilk test was conducted to assess the normality of quantitative data. Quantitative variables were compared using one-way ANOVA if normally distributed. Results:The LV attenuation of the six groups were (506±85), (513±77), (510±81), (456±74), (477±111), (462±43) HU, respectively. There was no significant difference among them ( F=2.249, P=0.054). SNR values of LV were 23±8, 20±5, 21±5, 19±4, 19±7, 19±4, and CNR values were 19±7, 17±4, 17±4, 16±4, 15±6, 15±4, respectively. There were no significant differences among them ( F=1.674, 1.736, all P>0.05). Under a single CTP scan, the radiation dose of 70, 80 and 100 kV groups were 1.6, 2.3 and 4.3 mSv, respectively. The does of the 70 kV group and 80 kV group were significantly lower than that of the 100 kV group, and the dose of the 70 kV group was also significantly lower than that of the 80 kV group (all P<0.001). Conclusions:The application of individualized scanning and contrast agent injection protocol based on IDR is feasible in myocardial CTP with successful image quality, and the radiation dose decreases significantly.

Objectives: . To compare the surgical outcomes of externally monitored and conventional buried flaps with the goal of determining the usefulness of external monitoring of buried flaps. Methods: . In this case-control study with propensity score matching, 30 patients were evenly divided into externally monitored buried flap and conventional buried flap groups. The total operative time for free flap reconstruction, the flap survival rate, the length of hospital stay, the initial time of a reliable visual assessment, complications, the final diet achieved, and the duration until diet initiation were compared between the groups. Results: . The mean operative time for reconstruction was 115 minutes (interquartile range, 85–150 minutes) and 142 minutes (interquartile range, 95–180 minutes) in the externally monitored and conventional groups, respectively (P= 0.245). The median length of hospital stay was 24 days (interquartile range, 18–30 days) and 27 days (interquartile range, 20–41 days) in the externally monitored and conventional groups, respectively (P=0.298). The median duration until diet initiation was 15 days (interquartile range, 15–21 days) and 18 days (interquartile range, 15–34 days) in the externally monitored and conventional groups, respectively (P=0.466). The final diet, initial time of a reliable visual assessment, and complications were comparable between the groups, but the external skin paddle provided an excellent visual assessment immediately postoperatively in all cases. Conclusion . The outcomes were comparable between the groups, indicating that externalization of the cutaneous component of a buried flap may be a straightforward and useful technique for monitoring a buried anterolateral thigh free flap in laryngopharyngeal reconstructions. The salvage and false-positive rates of compromised flaps should be compared in large subject groups in future studies to prove that the use of an external skin paddle improves flap monitoring.

Objective:To study the proportion and clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation (GAED) in gastric cancers showing an elevated serum alpha fetoprotein(AFP).Methods:A total of 724 resected gastric adenocarcinomas were collected from 2008 to 2018 at the 904 Hospital of Joint Service Support Force, and cases with pre-operative serum AFP >10 μg/L were screened. From the cases with elevated serum AFP, GAED cases were further evaluated based on morphology. Then the clincopathological features and immunohistochemical phenotypes of GAED were reviewed. In addition, the amplification of HER2 gene was detected with fluorescence in situ hybridization(FISH). When overall survival (OS) and progression-free survival (PFS) of GAED were analyzed, 289 cases ordinary gastric adenocarcinoma with normal serum AFP were employed as a control. Results:The percentage of GAED was 44% (11/25) in gastric cancers with elevated serum AFP. GAED was histologically tubular or papillary with clear cytoplasm, and some GAED cases showed cystadenoid structure similar to embryo sac (5 cases), homogeneous eosinophilic granules (4 cases) and intragland ulareosinophilic material (6 cases). All 11 GAED cases had lymph node metastasis. Liver metastasis and vascular thrombus were observed in 2 cases and 5 cases respectively. GAED was immunohistochemically positive for CDX2 (11/11), CD10 (8/11) and MUC2(3/11), which were intestinal epithelium differentiation markers. Meanwhile, primitive markers SALL4 (8/11), GPC3 (7/11) and AFP (5/11) were also expressed in GAED, and HER2 gene amplification was found in 3 cases (3/11) of GAED. Lastly, the PFS of GAED were significantly shorter than that of the control group ( P=0.02), while OS was not statistically different between these two groups ( P=0.99). Conclusions:Patients with GAED usually have a higher rate of elevated serum AFP in gastric adenocarcinoma, and the cancer exhibites features of both intestinal and primitive differentiation. As GAED is highly invasive, the prognosis of GAED may be poor. For GAED, the diagnosis of well-differentiated or moderately-differentiated adenocarcinoma should be avoided, because this diagnosis leads to underestimated malignant potential.

Objective To establish a rapid high performance liquid chromatography(HPLC)method for simultaneous determination of the concentration of total,free and reduced homocysteine (Hcy),glutathione(GSH),cysteine (Cys)and cys-teinylglycine (CysGly). Methods HPLC fluorescence detection method was established under the below conditions. The axci-tation and emission wavelengths was 330 nm and 380 nm respectively;the separation of thiols was achieved by using a C-18 column and the column temperature was 25 ℃;the mobile phase was gradient eluted with the three carboxyl ethyl phosphine (TCEP)as reducing agent and N-1- phenyl maleimide (NPM)as derivatization agent. The HPLC fluorescence detection meth-od was used to measure the thiol concentration in plasma of uraemia patients and healthy people. Results The linear range of total and free Hcy,GSH,Cys and CysGly were 1. 0 - 120. 0,2. 0 - 80. 0,10. 0 - 1500. 0 and 3. 0 - 240. 0 μmol·L - 1 respec-tively;the linear range of reduced Hcy,GSH,Cys and CysGly was 1. 25 - 50. 00,0. 10 - 8. 00,1. 25 - 50. 00 and 0. 01 -4. 00 μmol·L - 1 respectively. The intra-and inter-day ralative standard deviation were less than 5％;the recovery of this meth-od was 80. 1％ - 111. 7％ . The newly established HPLC fluorescence detection method was successfully applied to determine the total,free and reduced concentration of GSH,Cys,Hcy and CysGly in 34 uraemia patients and 32 healthy people. Conclu-sion A new HPLC fluorescence detection method for the determination of Hcy,GSH,Cys,and CysGly in plasma is developed and this method is accurate and reliable.

PURPOSE: Toll-like receptor 3 (TLR3) recognizes to viral double-stranded RNA and is involved in antiviral defenses. A probable role of TLR3 gene variants in the pathogenesis of aspirin-intolerant asthma (AIA) has been suggested. AIA patients present more frequent asthma exacerbations in which respiratory viral infections could be an exacerbating factor. IgG subclass deficiency was commonly present with bronchial asthma. Based on previous findings, we investigated whether TLR3 variants could affect IgG3 subclass deficiency in AIA. METHODS: We enrolled 279 AIA patients, 403 aspirin-tolerant asthma (ATA) patients, and 315 normal healthy controls (NC) in this study. TLR3 polymorphism at the promoter region -299698G>T was genotyped. The serum levels of IgG subclasses were determined by the single radial immunodiffusion method. Expressions of IgG3 and TLR3 on Epstein-Barr virus transformed-B cells isolated from asthmatic patients were evaluated by flow cytometry to investigate B-cell functions. RESULTS: The TLR3 -299698 T allele was significantly associated with severity and IgG3 deficiency in the AIA group (P=0.044 and P=0.010, respectively), but not in the ATA group. IgG3 expression on B cells from asthmatics with IgG3 deficiency was significantly lower compared to those without (P=0.025). There was a positive correlation between IgG3 expression levels on B cells and serum IgG3 levels (r 2=0.434, P=0.002). CONCLUSION: These results suggest that the TLR3 -299698G>T polymorphism may be associated with IgG3 subclass deficiency and severity in AIA.
Alleles ; Asthma* ; B-Lymphocytes ; Flow Cytometry ; Herpesvirus 4, Human ; Humans ; Immunodiffusion ; Immunoglobulin G* ; Methods ; Polymorphism, Genetic ; Promoter Regions, Genetic ; RNA, Double-Stranded ; Toll-Like Receptor 3

Sclerosing mesenteritis is a rare disease presenting as chronic inflammation and fibrosis of mesentery around the small and large intestine. And in most cases, it shows indolent and benign clinical course resulting in favorable prognosis. It is often diagnosed through characterized radiologic finding in abdominal examinations including computed tomography scan. However, it is important to rule out other conditions involving mesentery when diagnosing sclerosing mesenteritis. In the case of malignancy, the method of treatment and prognosis can be completely different therefore thorough examinations are essential. We herein report a 75-year-old male who suffered from frequent diarrhea and weight loss. Initially, he was diagnosed with sclerosing mesenteritis through abdominal computed tomography scan showing "misty" soft-tissue attenuation around the mesenteric vessel. However, follow up positron emission tomography scan and biopsy finding confirmed the common bile duct cancer with lymph node metastasis.
Aged ; Biopsy ; Cholangiocarcinoma* ; Common Bile Duct ; Diarrhea ; Fibrosis ; Follow-Up Studies ; Humans ; Inflammation ; Intestine, Large ; Lymph Nodes* ; Male ; Mesentery ; Methods ; Neoplasm Metastasis* ; Panniculitis ; Panniculitis, Peritoneal* ; Positron-Emission Tomography ; Prognosis ; Rare Diseases ; Weight Loss