An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

Anti neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a systemic disease characterized by small vessel wall inflammation and cellulose necrosis mediated by ANCA. Renal injury caused by AAV is called ANCA-associated glomerulonephritis (AAGN). The paper reported a case of AAV with renal damage combined with human immunodeficiency virus (HIV) infection. The patient was an elderly male with clinical manifestations of hematuria and uremia. Renal pathological examination showed AAV and renal injury. This case is the first report in China while reviewing the relevant literature, and it is still inconclusive whether this is an overlap of the two diseases or a specific pathological type of HIV-associated nephritis. We believe that AAV has the potential to occur in HIV-infected patients, so clinicians should not ignore the phenomenon of ANCA positivity in HIV-infected patients, and the follow-up of such patients needs to be enhanced. Clinical and renal pathological examinations are the main methods to diagnose HIV infection with AAV. At the same time, there are no clear guideline guidelines on how to administer immunosuppressive therapy for such patients who have immunodeficiency and are at higher risk of opportunistic infections, and in whom to make the best possible outcomes.

Combing with the professional characteristics of imaging technology, Radiological Department of West China Hospital, Sichuan University established the STAR training model for imaging technologists to cultivate the scientific research quality of young technicians, which includes sub-professional group training, tutor responsibility system, arrangement of research time, and reading-film session of technologists. Practice shows that this training model has made a series of achievements so far, such as that the number of publishing articles, funds application, authorized patents and oral presentation at international congress has been significantly increased. In addition, there is a high recognition of the STAR training model among young imaging technologists. Therefore, the STAR model can stimulate the scientific research passion of young technologists, and improve their scientific research capability.

ObjectiveTo explore and establish the liver injury risk prediction model of indirect toxicity of Chinese medicinals under the condition of compound formulas， and provide new ideas and methods for the study of evaluation of liver injury of Chinese medicinals based on indirect toxicity. MethodsTaking Buguzhi （Fructus Psoraleae） pre-parations as model drug， the combined Chinese medicinals with Buguzhi （Fructus Psoraleae） of high frequency are screened out， and their components and action targets were obtained through TCMSP， TCMIP and PharmMapper databases. The association strength value and risk value of Chinese medicinals that acted on the nuclear factor κB （NF-κB） pathway were analyzed. For those having greater values than the median association strength value and risk value were regarded as indirect Chinese medicinals of liver injury risk. In this way， a prediction model of liver injury risk of Chinese medicinals was constructed based on immune activation-related indirect liver injury process （taking NF-κB pathway as an example）. And verification of the prediction model was performed using Heshouwu （Radix Polygoni Multiflori） preparations. ResultsThe prediction model of liver injury risk based on important immunoactivated pathway （taking NF-κB pathway as an example） found that Yinyanghuo （Herba Epimedii） （association strength value = 0.18， risk value = 0.25） was a Chinese medicinal with potential risk of indirect liver injury within Buguzhi （Fructus Psoraleae） prepartions， which may increase the risk of liver injury by positively regulating Bruton's tyrosine kinase （Btk） and protein kinase C theta （PKCθ） on NF-κB pathway. Further verification of prediction model by Heshouwu （Radix Polygoni Multiflori） preparations showed that Buguzhi （Fructus Psoraleae） （association strength value = 0.25， risk value = 0.33） and Tusizi （Semen Cuscutae） （Semen Cuscutae， association strength value = 0.34， risk value = 0.33） may increase the liver injury risk of Heshouzu. ConclusionThe liver injury risk prediction model of indirect toxicity of Chinese medicinals has been constructed in this study， providing metho-dological reference for the identification of Chinese medicinals of indirect liver injury risk under the condition of compound formulas.

Background: Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction. Objectives: To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils. Methods: We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils. Results: DEX injection markedly increased blood glucose, TP and TC levels, the Ca 2+ /P 5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels. Conclusions DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

Objective:To explore the application effect of case-based learning (CBL) combined with problem-based learning (PBL) teaching model in refresher training of medical imaging technologists.Methods:The study recruited 46 imaging technologists trained in radiology department in the Batch 2017 and Batch 2018 of West China Hospital of Sichuan University. They were divided into 2 groups: experimental group (23 persons) and control group (23 persons). CBL combined with PBL teaching method was used in the experimental group, and traditional lecture-based learning (LBL) method was used in the control group. The results of attitude evaluation, staged exminations, graduation assessment and operational skill tests were compared between the two groups, and the questionnaire survey was performed to test the affirmation of self-worth of the two groups of interns. SPSS 17.0 was used for chi-square test, independent t test, and Mann-Whitney U test. Results:Theoretical examination results at the second stage, the third stage, completion and operational examination results in the experimental group were significantly higher than those in the control group [(91.17±2.59) vs. (85.26±3.03), (92.00±1.86) vs. (87.43±3.23), (92.39±2.08) vs. (87.04±2.93), (85.70±5.48) vs. (80.87±5.57), P<0.05]. The questionnaire survey showed that such 7 aspects as the stimulation of subject interest, the cultivation of exploration spirit, the exercise of self-learning ability, the establishment of clinical ideas, the analysis of difficult problems, the mastering of practical operations, and the affirmation of self-worth in the experimental group were better than those in the control group, with significant difference ( P<0.05), while the consolidation of theoretical knowledge of the experimental group was not statistically different from the control group ( P>0.05). Conclusion:The reasonable application of CBL combined with PBL teaching model in refresher training of medical imaging technologists is helpful to improve their learning enthusiasm, self-learning ability, clinical analysis ability, practical operation ability, and long-term consolidation of theoretical knowledge.

Background: Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) in radicular pain and its possible mechanisms. Methods: An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of proand anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay. Results: Spinal expression of TLR4 and p-NF-κB (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)-1β, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn. Conclusions The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.

Clinical practice of medical imaging technology undergraduates is a key link in the transformation from imaging technology students to imaging technologists. However, there are a series of problems leading to poor practice effect, e.g., imaging technology involves a lot of learning contents, and the teachers' level is uneven. Based on the above problems, some improvements have been implemented, including the establishment of the admission lecture system and tutor responsibility system, application of pluralistic teaching methods, standardizing the examination system of interns, flexible adjustment of practice time arrangements, training of practice teaching team, and so on. Finally, the quality and effect of undergraduate practice teaching in medical imaging technology has been improved significantly.

Background: Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) in radicular pain and its possible mechanisms. Methods: An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of proand anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay. Results: Spinal expression of TLR4 and p-NF-κB (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)-1β, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn. Conclusions The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.

Objective:To explore the application effect of case-based learning combined with problem-based learning teaching model in refresher training of medical imaging technologists.Methods:The study recruited 46 imaging technologists trained in radiology department in the Batch 2017 and Batch 2018 of West China Hospital of Sichuan University. They were divided into 2 groups: experimental group (23 persons) and control group (23 persons). Case-based learning combined with problem-based learning teaching method was used in the experimental group, and traditional lecture-based learning method was used in the control group. 2 test was used for sex distribution comparisons between the two groups, and independent t test was conducted to compare the differences in age, working years, entrance examination results, attitude rating scores, stage examination scores, completion examination scores, and operational examination scores between the two groups. Mann-Whitney U test was used for comparisons of non-parametric variables between the two groups, such as qualifications, occupation title, and questionnaire results.Results:Theoretical examination results at the second stage, the third stage, completion and operational examination results in the experimental group were higher than those in the control group [(91.17±2.59) vs. (85.26±3.03), (92.00±1.86) vs. (87.43±3.23), (92.39±2.08) vs. (87.04±2.93), (85.70±5.48) vs. (80.87±5.57), P<0.05]. The questionnaire survey showed that the stimulation of subject interest, the cultivation of exploration spirit, the exercise of self-learning ability, the establishment of clinical ideas, the analysis of difficult problems, the mastering of practical operations, and the affirmation of self-worth in the experimental group were better than those in the control group, with significant difference [4(3, 4) scores vs. 3(2, 3) scores, 4(3, 4) scores vs. 2(2, 3) scores, 3(3, 4) scores vs. 2(2, 3) scores, 3(3, 4) scores vs. 3(2, 3) scores, 3(3, 4) scores vs. 2(2, 3) scores, 4(3, 4) scores vs. 3(2, 3) scores, 4(3, 4) scores vs. 3(2, 3) scores, P<0.05], while the consolidation of theoretical knowledge of the experimental group was not different from the control group [3(2, 3) scores vs. 3(2, 3) scores, P>0.05]. Conclusions:The reasonable application of case-based learning combined with problem-based learning teaching model in refresher training of medical imaging technologists is helpful to improve their learning enthusiasm, self-learning ability, clinical analysis ability, practical operation ability, and long-term consolidation of theoretical knowledge, and it also can contribute to affirmation of self-worth.