AIM: To detect the mRNA and protein level of HIF-1 alpha in the tissues of rat's radiated mucosa. METHODS: The left buccal mucosa was irradiated and excised. The right buccal mucosa was excised to serve as own control tissue. The mRNA of HIF-1 alpha was determined by using the semi quantitative RT-PCR. SABC method was employed to immunostain and to elucidate the localization, intensity and distribution of HIF-1 alpha protein.RESULTS: A Sprague-Dawley rat's model of radiation-induced oral mucositis (ROM) was successfully established. The results of RT-PCR indicated that the left buccal mucosa expressed HIF-1 alpha mRNA while the right buccal mucosa did not or seldom expressed it. Immunohistochemical analysis of HIF-1 alpha demonstrated that the left side mucosa expressed HIF-1 alpha protein.CONCLUSION: The mucosa of ROM expresses the mRNA and protein of HIF-1 alpha. The expressions of HIF-1 alpha are correlated with the severity of ROM.

OBJECTIVETo study the karyotype of four Ephedra plants in order to provide the cytologic evidence for the genetic diversity and identification genetic resources of Ephedra.

METHODThe roots of germinating seeds were used to study the karyotype of four Ephedra plants by staining and slide-preparing technique of mitotic chromosomes.

RESULTthe optimal root-sampling time was about 10: 20 - 10:40 am. Using 0.002 mol x L(-1) 8-Hydroxyquinoline to pretreating the intravital root tips, the optimal pretreatment time for E. Sinica, E. intermedina, E. equisetina and E. przewalskii was 4, 5, 4.5 and 3.5 h, respectively. E. przewalskii and E. equisetina were diploid, E. Sinica and E. intermedina were belonged quadruple. The karyotype formulae of the four species were 2n = 2x = 14 = 2M + 8m + 4sm, 2n = 2x = 14 = 10m + 4st, 2n = 4x = 28 = 20m (2SAT) +8st, and 2n = 4x = 28 = 20m (SAT) + 6st + 2sm, respectively.

CONCLUSIONAll the karyotypes of four Ephedra species were 2A type, which was the symmetric karyotype.

Objective: To explore the diagnostic performance of the most recent 2018 version of liver reporting and data system (LI-RADS) on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI to diagnose hepatocellular carcinoma (HCC) in high-risk patients. Methods: From July 2015 to September 2018, 130 consecutive high-risk patients with 134 focal liver lesions were retrospectively enrolled in our center and underwent Gd-EOB-DTPA-enhanced MRI and subsequent hepatectomy within 1 month. Two independent radiologists blindly reviewed the preoperative MR images of all patients, and determined the presence of major features, ancillary features and the LI-RADS categories according to the version 2018 LI-RADS of each liver observation. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index and accuracy of the 2018 version of LI-RADS were evaluated with postoperative histopathological results as references. The inter-observer agreement between the two radiologists was tested by Kappa analysis. Results: The Kappa value of the LI-RADS categories between two radiologists was 0.628 (95%CI: 0.565 to 0.691). The sensitivity, specificity, Youden index values and accuracy of LR-5 by the two reviewers were 80.4% (78/97), 87.6% (85/97); 75.7% (28/37), 73.0% (27/37); 0.560 8, 0.605 9; 79.1% (106/134), 83.6% (112/136), respectively. These measures of LR-4+LR-5 were 91.8% (85/97), 96.9% (94/97); 67.6% (25/37), 67.6% (25/37); 0.605 9, 0.644 6; 82.1% (110/134), 88.8% (119/134), respectively. Conclusion Version 2018 LI-RADS demonstrated high sensitivity and accuracy to diagnosis HCC in high-risk patients on Gd-EOB-DTPA enhanced MRI.

Objective To explore the diagnostic performance of the most recent 2018 version of liver reporting and data system (LI?RADS) on gadolinium?ethoxybenzyl?diethylenetriamine pentaacetic acid (Gd?EOB?DTPA) enhanced MRI to diagnose hepatocellular carcinoma (HCC) in high?risk patients. Methods From July 2015 to September 2018, 130 consecutive high?risk patients with 134 focal liver lesions were retrospectively enrolled in our center and underwent Gd?EOB?DTPA?enhanced MRI and subsequent hepatectomy within 1 month. Two independent radiologists blindly reviewed the preoperative MR images of all patients, and determined the presence of major features, ancillary features and the LI?RADS categories according to the version 2018 LI?RADS of each liver observation. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index and accuracy of the 2018 version of LI?RADS were evaluated with postoperative histopathological results as references. The inter?observer agreement between the two radiologists was tested by Kappa analysis. Results The Kappa value of the LI?RADS categories between two radiologists was 0.628 (95%CI: 0.565 to 0.691). The sensitivity, specificity, Youden index values and accuracy of LR?5 by the two reviewers were 80.4% (78/97), 87.6% (85/97); 75.7% (28/37), 73.0% (27/37); 0.560 8, 0.605 9; 79.1% (106/134), 83.6% (112/136), respectively. These measures of LR?4+LR?5 were 91.8% (85/97), 96.9% (94/97); 67.6% (25/37), 67.6% (25/37); 0.605 9, 0.644 6; 82.1% (110/134), 88.8% (119/134), respectively. Conclusion Version 2018 LI?RADS demonstrated high sensitivity and accuracy to diagnosis HCC in high?risk patients on Gd?EOB?DTPA enhanced MRI.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, and represents a significant global health burden with rising incidence rates, despite a more thorough understanding of the etiology and biology of HCC, as well as advancements in diagnosis and treatment modalities. According to emerging evidence, imaging features related to tumor aggressiveness can offer relevant prognostic information, hence validation of imaging prognostic features may allow for better noninvasive outcomes prediction and inform the selection of tailored therapies, ultimately improving survival outcomes for patients with HCC.

Objective:To establish and validate a clinical and CT radiomics combined model for predicting lymph node metastasis (LNM) risk in patients with hilar cholangiocarcinoma (HCCA).Methods:This was a case-control study. Data from 158 pathologically confirmed HCCA patients between January 2016 and January 2022 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Using stratified random sampling, the patients were randomly divided into a training set ( n=95) and an internal validation set ( n=63) at a 6∶4 ratio. According to postoperative pathology, 31 LNM-positive cases and 64 LNM-negative cases were in the training set, and 22 LNM-positive cases and 41 LNM-negative cases were in the internal validation set. A cohort of 50 HCCA patients was retrospectively collected from West China Hospital of Sichuan University between October 2018 and June 2021 as an external validation set, including 21 LNM-positive and 29 LNM-negative cases. Clinical features were selected by multivariate logistic regression analysis to establish a clinical model. Radiomics features were extracted from portal venous phase CT images using 3D Slicer software. A radiomics model was developed using the least absolute shrinkage and selection operator regression algorithm. A clinical-radiomics model was constructed by integrating clinical features and Radscore, and a nomogram was developed. The prediction performance of models was evaluated by the area under the receiver operating characteristic curve (AUC). The AUC values were compared using the DeLong test. Calibration curves and decision curves were plotted to assess calibration and clinical net benefit. Results:Clinical N (cN) staging was an independent risk factor for LNM ( OR=6.86, 95% CI 2.70-18.49, P<0.001). Totally 12 optimal features were selected to construct the radiomics model, and the clinical-radiomics nomogram model was constructed by combining cN staging and Radscore. In the external validation set, the AUC (95% CI) of the clinical model, radiomics model, and clinical-radiomics nomogram were 0.706 (0.576-0.836), 0.768 (0.637-0.899), and 0.803 (0.680-0.926), respectively. The nomogram achieved higher AUC than clinical and radiomics models with statistical significance ( Z=2.01, 2.21; P=0.044, 0.027). The calibration and decision curves demonstrated good model fit, providing clinical net benefits for patients. Conclusion:The clinical-radiomics nomogram model combining cN staging and CT radiomics features can effectively predict LNM risk in HCCA patients.

Guillain-Barré syndrome (GBS) is an acute onset immune-mediated polyradiculoneuropathy, and it is the most frequent cause of acute flaccid paralysis.Intravenous immunoglobulin and plasma exchange are proved to be an effective treatment.Despite the efficacy of immunotherapy, a significant number of patients have a poor prognosis, leaving behind severe dysfunction and even death.Therefore, biomarkers and prognostic models are needed to accurately predict outcome, which could help the early recognition of patients with poor outcomes, which may potentially be-nefit from individualized treatments.So, new development of immunotherapy and prognostic evaluation of GBS were summarized in this paper, in order to provide the evidence for clinical diagnosis and treatment.

Objective:To investigate the incidence and determinants of vaccine hesitancy towards national immunization program in China and understand the current status of parents' hesitancy to different vaccines used in national immunization program.Methods:A cross-sectional survey was conducted in Beijing, Sichuan and Gansu. The methods of proportional probability sampling and convenience sampling were used to select the eligible study subjects for questionnaire surveys.Results:A total of 3 592 parents were enrolled in the study, in whom 38.22% fully accepted all the vaccines, 59.35% agreed to let their children to receive all the vaccines but showed slight concern, and 2.42% had hesitancy to the vaccines. The vaccine with the most hesitancy was polio vaccine (0.89%), followed by diphtheria pertussis tetanus vaccine (0.70%) and hepatitis A vaccine (0.64%). The dominant reason for vaccine hesitancy was the risk-benefit perception of vaccination (31.03%), followed by the low awareness of the parents (21.84%) and the inconvenience caused by distance and time (21.84%).Conclusions:The incidence of vaccine hesitancy towards national immunization program was low in parents in China, but over 50% of the parents showed concern to the vaccines. It is essential to improve the service quality of national immunization program and strengthen the health education about the vaccination to reduce the incidence of vaccine hesitancy in parents.

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.