Objective To investigate the effect of Yinchenhao decoction on renal oxidative stress injury in rats with obstructive jaundice and its association with the regulation of the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear translocation. Methods A total of 32 male Sprague-Dawley rats were randomly divided into sham-operation group (S group), model group (O group), low-dose Yinchenhao decoction group (LY group), and high-dose Yinchenhao decoction group (HY group), with 8 rats in each group. For the rats in the S group, the upper common bile duct was isolated without ligation, and for those in the other groups, double ligation of the middle and upper 1/3 of the common bile duct was performed to establish a model of obstructive jaundice. After 7 days, the rats in the LY group and the HY group were given Yinchenhao decoction by gavage at a dose of 6.3 and 18.9 mL/kg, respectively, while those in the S and O groups were given an equal volume of distilled water by gavage every day for 7 consecutive days, and the rats were treated on day 14. ELISA was used to measure the serum levels of total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), and creatinine (Cr); spectrophotometry was used to measure the activity of the oxidative stress factors superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue; quantitative real- time PCR and Western blotting were used to measure the mRNA and protein expression levels of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in renal tissue; immunohistochemistry was used to measure observe the nuclear translocation of Nrf2 protein in renal tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further pairwise comparison within groups. Results Compared with the S group, the O group had significant increases in the levels of TBil, DBil, ALT、GGT, BUN, and Cr, a significant reduction in the activity of SOD, and a significant increase in the level of MDA (all P < 0.05). Compared with the O group, the LY group and the HY group had significant reductions in liver and renal function parameters, a significant increase in the activity of SOD, and a significant reduction in the level of MDA (all P < 0.05). Compared with the S group, the O group had significant reductions in the mRNA and protein expression levels of Nrf2 and NQO1 in renal tissue (all P < 0.05), and compared with the O group, the LY group and the HY group had significant increases in the mRNA and protein expression levels of Nrf2 and NQO1 (all P < 0.05), while there was no significant difference in the protein expression level of Keap1 between groups ( P > 0.05). Compared with the S group, the O group had a significant reduction in the positive rate of Nrf2 in cell nucleus in renal tissue ( P < 0.05), and compared with the O group, the LY group and the HY group had a significant increase in the positive rate of Nrf2 in cell nucleus ( P < 0.05). Conclusion Yinchenhao decoction can effectively alleviate renal injury caused by obstructive jaundice, possibly by upregulating the protein expression of Nrf2 in renal tissue and regulating the nuclear translocation of Nrf2 protein, so as to mediate the protein expression of downstream NQO1, regulate oxidative stress response caused by obstructive jaundice, and thereby alleviate renal injury in rats.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Objective:To explore the value of radiomics model based on intratumoral and peritumoral early dynamic contrast-enhanced (DCE) MRI for identifying benign and malignant in breast imaging reporting and data system (BI-RADS) 4 tumors.Methods:A total of 191 patients diagnosed with BI-RADS 4 breast tumors by breast MRI examination with clear pathological diagnosis from January 2016 to December 2020 in the First Affiliated Hospital of Bengbu Medical College were analyzed retrospectively, including 77 benign and 114 malignant cases, aged 23-68 (46±10) years. The one-slice image with the largest area of the lesion of the second stage DCE-MRI images was selected to outline the region of interest, and automatically conformal extrapolated by 5 mm to extract the intra-tumoral and peritumoral radiomics features. The included cases were randomly divided into training and testing cohorts in the ratio of 8∶2. The statistical and machine learning methods were used for feature dimensionality reduction and selection of optimal radiomics features, and logistic regression was used as the classifier to establish the intratumoral, peritumoral, and intratumoral combined with peritumoral radiomics models. The independent risk factors that could predict the benignity and malignancy of breast tumors were retained as clinical-radiological characteristics by univariate and multivariate logistic regression to establish a clinical-radiological model. Finally, the intratumoral and peritumoral radiomics features were combined with clinical-radiological features to develop a combined model of the three. The receiver operating curve was used to analyze the predictive performance of each model and calculate the area under the curve (AUC),the AUC was compared by DeLong test. The stability of the three-component combined diagnostic model was tested by 10-fold cross-validation, and the model was visualized by plotting nomogram and calibration curves.Results:In the training cohort, the AUC of the three-component combined model for identifying benign and malignant BI-RADS 4 breast tumors was significantly higher than that of the intratumoral radiomics model ( Z=3.38, P<0.001), the peritumoral radiomics model ( Z=4.01, P<0.001), the intratumoral combined with peritumoral radiomics model ( Z=3.11, P=0.002), and the clinical-radiological model ( Z=3.24, P=0.001). And the AUC, sensitivity, specificity, accuracy, and F1-score of the three-component combined model were 0.932, 91.2%, 86.9%, 87.0% and 0.89, respectively. In the testing cohort, the three-component combined model also had the highest AUC value (0.875), and diagnostic sensitivity, specificity, accuracy and malignancy F1-score were 95.7%, 62.5%, 76.9%, and 0.89, respectively. The AUC calculated by 10-fold cross-validation was 0.90 (0.85-0.92), and the predicted curve of the three-component combined model in the calibration curve was in good agreement with the ideal curve. Conclusion:The three-component combined diagnostic model based on the intratumoral and peritumoral radiomics features and clinical-radiological features of early DCE-MRI has good performance and stability for identifying the benign and malignant in BI-RADS 4 breast tumors, and it can provide guidance for clinical decision non-invasively.

Objective:To study the risk factors of necrotizing enterocolitis (NEC) after surgery for intestinal atresia.Method:From August 2013 to June 2020, children with intestinal atresia receiving surgery in our hospital were retrospectively reviewed. The patients were assigned into NEC group and non-NEC group according to the occurrence of postoperative NEC. Demographic data and clinical characteristics were summarized and the risk factors for postoperative NEC were analyzed using Logistic regression analysis method.Result:A total of 96 infants were enrolled and NEC occurred in 13 patients (13.5%) after surgery for intestinal atresia. Compared with the non-NEC group, the NEC group were diagnosed of intestinal atresia [4.0(1.5,6.0)d vs. 1.4(0,2.0)d, P<0.001] and received surgery [4.8(2.0,7.0)d vs. 3.1(1.0,4.0)d, P=0.034] at later ages. The incidences of complex intestinal atresia [76.9%(10/13) vs. 44.6%(37/83), P=0.030] and blood transfusion [46.2%(6/13) vs. 13.3%(11/83), P=0.007] in the NEC group were higher than the non-NEC group. Logistic regression analysis showed that the age of initial diagnosis of intestinal atresia ( OR=3.346, 95% CI 1.493~7.500, P=0.003), complex intestinal atresia ( OR=9.052, 95% CI 1.119~73.209, P=0.039) and blood transfusion ( OR=6.835, 95% CI 1.399~33.380, P=0.018) were independent risk factors for postoperative NEC. Conclusion:Patients with delayed diagnosis of intestinal atresia, complex intestinal atresia and blood transfusion within 48 hours after surgery should be monitored for the occurrence of postoperative NEC.

Prostate cancer (PCa) patients who progress to metastatic castration-resistant PCa (mCRPC) mostly have poor outcomes due to the lack of effective therapies. Our recent study established the orphan nuclear receptor ROR

Objective:To investigate the cognitive status of professionalism among medical college students and ways to cultivate physician professionalism.Methods:According to the literature and interview, we made the questionnaire on the cognition of physician professionalism among medical students. A total of 512 valid questionnaires (including e-questionnaires) were collected from medical students of Shantou University Medical College and Qingdao University Medical College of Shandong Province from May to September, 2017. SPSS 20.0 software was used to perform the normality and single-sample t-test on physician professionalism, professional cognition, professional emotion and professional willingness. Quantitative data was analyzed by cross-table chi-square test and mean-standard deviation. Results:The professional cognition scored lowest (3.62±0.50) in the three dimensions, the professional willingness scored the highest (4.35±0.58), and the professional emotional scored in the middle (4.05±0.48). There was significant difference in physician professionalism among medical students with different family background ( P<0.05), but no statistical difference in gender and school system. Conclusion:The results demonstrate a low-to-medium level of physician professionalism in medical students. We suggest to cultivate and promote physician professionalism from the aspects of emphasis on objectivity, and cultivation of humanism and service consciousness.

Objective:To investigate the effect of situational simulation combined with video feedback in cardiopulmonary and abdominal clinical probation of diagnostics.Methods:Two hundred and twenty-four clinical undergraduates from the second affiliated hospital of Guangxi Medical University were randomized into the experimental group ( n=112) and the control group ( n=112). The experimental group applied situational simulation combined with video feedback methods in the cardiopulmonary and abdominal clinical probation. In other words, according to the assignment of diseases, two students played the role of "physician and patient" and conducted corresponding consultation and physical examination, in which the positive and negative video feedback were integrated to standardize students' physical examination skills. The control group adopted conventional teaching method. The teaching effect of the two groups was evaluated through unified and standardized scores of theoretical tests, cases analysis, and clinical skills operation, and the experimental group was conducted anonymous questionnaires to 112 students. SPSS 22.0 was used to perform the t test. Results:The evaluation results show that the average scores of theoretical tests (90.12±0.94), cases analysis (9.30±0.10) and physical examination (93.50±0.72) in the experimental group are higher than those of the control group, (83.20±1.66), (8.10±0.11), (85.00±1.75), respectively, with statistical significance ( P<0.05). All 112 questionnaires were collected, with an effective rate of 100%. The percentage of "yes" respondents is as follows, 91.1% of "Enhancing the mastery and application of knowledge"; 97.3% of "Cultivating clinical thinking"; 87.5% of "Improving doctor-patient communication skills"; however, there are 93.8% students believe that this new teaching approach takes more time to prepare before class, consequently, their initiative and enthusiasm of study and learning interest have slid into decline, with percentage of 80.4% and 83.0%, respectively. Conclusion:The teaching method of situational simulation and video feedback in cardiopulmonary and abdominal clinical probation of diagnostics is beneficial to enhance students' understanding and mastery of theoretical knowledge, standardize physical examinations, cultivate clinical thinking ability and improve the doctor-patient communication skills. However, it takes a lot of time for students to prepare before class. If they fail to make reasonable arrangements, the teaching effect will be half the effort and students' initiative and enthusiasm of learning will be reduced.

Objective:To investigate the reparative efficacy and mechanism of pressure-adjustable macroporous antibacterial hydrogel in the treatment of infected wounds.Methods:Staphylococcus aureus was used to establish wound infection models in healthy C57BL/6 mice. The models were divided into 3 groups subjected to 3 different treatments: a negative control group with no hydrogel treatment (group A), a control group treated by common medical hydrogel (group B) and an experiment group treated by pressure-adjustable macroporous antibacterial hydrogel (group C). On days 1, 3, 6, 9 and 12, the effects of 3 treatments were compared on the wound area and the number of bacterial colonies under scab, on the apoptosis of fibroblasts based on the changes of type Ⅰ procollagen, and on the inhibition of inflammation during wound repair by detecting the expression of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α).Results:On days 1 and 3, there was no significant difference between the 3 groups in the wound area ( P>0.05), but on days 6, 9 and 12, there were significant differences between the 3 groups in the wound area ( P<0.05). On day 6, the wound areas in group B (1.23 cm 2 ± 0.16 cm 2) and in group C (1.14 cm 2 ± 0.12 cm 2) were significantly smaller than that in group A (1.56 cm 2 ± 0.16 cm 2) ( P<0.05), but there was no significant difference between groups B and C ( P>0.05). On days 9 and 12, the wound areas in group B (0.97 cm 2 ± 0.13 cm 2 and 0.76 cm 2 ± 0.10 cm 2) and in group C (0.66 cm 2 ± 0.06 cm 2 and 0.48 cm 2 ± 0.07 cm 2) were significantly smaller than those in group A (1.49 cm 2 ± 0.11 cm 2 and 1.39 cm 2 ± 0.13 cm 2), and those in group C were significantly smaller than those in group B (all P<0.05). On day 1, there was no significant difference between the 3 groups in the number of bacterial colonies under scab ( P>0.05). On days 3, 6, 9 and 12, the numbers of bacterial colonies under scab in groups B and C were significantly smaller than that in group A ( P<0.05), and that in group C was significantly smaller than that in group B ( P< 0.05). The nucleic acid electrophoresis showed that the grayscale bands in group C were significantly darker than those in groups A and B. The early apoptosis rate of the fibroblasts in group C[low-right positive fluorescence (LR%): 9.72%] was significantly lower than that in group A (43.99%) and that in group B (38.43%), and that in group B was significantly lower than that in group A ( P<0.05). On day 12, the ratio of the gray values of IL-6 and β-actin (0.64 ± 0.10) and the ratio of the gray values of TNF-α and β-actin (0.34 ± 0.05) in the fibroblasts in group C were significantly higher than those in group A (1.22 ± 0.21 and 0.60 ± 0.14) and in group B (0.88 ± 0.02 and 0.41 ± 0.06) ( P<0.01). Conclusion:The pressure-adjustable macroporous antibacterial hydrogel is an effective treatment of infected wounds and its mechanism may be related to the reduced apoptosis of fibroblasts.

Objective To investigate the expression change and their clinical role of triggering receptor expressed on myeloid cells-1 (TREM-1) in patients with severe thoracic trauma.Methods A prospective cohort study was conducted to analyze the clinical data of 52 patients with severe thoracic trauma (trauma group) hospitalized from October 2016 to May 2017.The peripheral anticoagulant blood samples were collected at days 1,3,5,7 and 14 after trauma.Meanwhile,10 healthy volunteers were enrolled in control group and their blood samples were collected once.According to injury severity score (ISS),the patients were divided into ISS low-score group (＜ 20 points,n =15) and high-score group (≥20 points,n =37).The patients were assigned to traumatic non-sepsis group (n =34) and traumatic sepsis group (n =18) by the latest definition and standard of sepsis 3.0 issued by the Society of Critical Care Medicine (SCCM)/European Society of Intensive Care Medicine (ESICM).The expressions of TREM-1 on neutrophils and monocytes were measured by flow cytometry.Pairwise comparisons were done between trauma group and healthy volunteers,ISS low-score group and ISS high-score group,and traumatic sepsis group and non-sepsis group,respectively.The accuracy of traumatic sepsis prediagnosis by TREM-1 was evaluated by the area under receiver operating characteristic curve (AUC).Results Trauma group had 41 males and 11 females,with age of (45.9 ± 12.4) years,Abbreviated Injury Scale (AIS) of (3.5 ± 0.6) points and Injury Severity Score (ISS) of (23.6 ± 8.5) points.Control group had eight males and two females,with the age of(29.1 ± 2.8) years.Compared to control group,trauma group had slightly lower TREM-1 expressions in neutrophils and significantly higher expressions in monocytes at days 1 to 14 (all P ＜ 0.01).ISS high-score group had slightly lower TREM-1 expressions in neutrophils than ISS low-score group at days 1 to 7,with significant difference at day 1 (P ＜ 0.05).ISS high-score group had slightly higher TREM-1 expressions in monocytes than ISS lowscore group at days 1 to 14,with significant difference at day 14 (P ＜ 0.05).Compared to traumatic non-sepsis group,traumatic sepsis group had significantly lower TREM-1 expressions in neutrophils at days 1 to 14 (all P ＜ 0.05).Traumatic sepsis group had slightly lower expressions in monocytes than traumatic non-sepsis group at days 1 to 7,with significant difference at day 3 (P ＜ 0.05).AUC and 95％ CI evaluating the role of neutrophils TREM-1 in traumatic sepsis prediagnosis were 0.852 (0.738,0.966) at day 1,0.835 (0.721,0.948) at day 3,0.797 (0.654,0.939) at day 5,0.756 (0.599,0.914) at day 7,and 0.707 (0.525,0.888) at day 14,respectively.Conclusions After severe thoracic trauma,the expressions of TREM-1 are decreased in neutrophils but increased in monocytes.TREM-1 might be used to assess the injury severity and has certain value in prediagnosis for traumatic sepsis.

Objective To study and prepare the monoclonal antibody library against human FXYD6 functional region,to screen the hybridoma cell lines secreting the monoclonal antibodies against intracellular or extracellular region of human FXYD6,and to identify the biological function of monoclonal antibody against extracellular domain.Methods FXYD6 functional region recombinant protein which did not contain the transmembrane region was prokaryotically expressed,purified,and FXYD6 recombinant protein was used to immunize BALB/c mice.Then splenocytes after immunization were fused with myeloma cells SP2/0.After several rounds of screening and cloning,the hybridomas which secreted the antibodies against the extracellular domain or the intracellular domain of human FXYD6 were established.The antibody specificity and subtype were identified with indirect ELISA,western blot and immunohistochemistry.The monoclonal antibodies against the extracellular domain which recognized the native conformation were screened with flow cytometry.The antibody against extracellular region was prepared with the ascites revulsion method and purified.The affinity constants were measured with indirect ELISA.The function of extracellular monoclonal antibody was detected by HepG2 cell line with high expression of FXYD6.Results The hybridoma cell library which secreted the monoclonal antibody against extracellular domain or the intracellular domain of human FXYD6 was successfully obtained,and extracellular region monoclonal antibodies with the functional blocking were prepared.Conclusion The prepared anti-human FXYD6 extracellular monoclonal antibodies could inhibit HepG2 cell proliferation.