Bisphenol F exposure induces depression-like changes: Roles of the kynurenine metabolic pathway along the "liver-brain" axis.

Bisphenol F (BPF), one of the major alternatives of Bisphenol A (BPA), is becoming extensively used in industrial production with great harm to human beings and environment. Recent studies have revealed that environmental exposure is crucial to the initiation and development of depression. Thereby, the aim the present study is to ascertain the correlationship between the BPF exposure and depression occurrence. In the current study, BPF strikingly triggered depression-like changes in mice through the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST), accompanied by the perturbation of the kynurenine (KYN) metabolic pathway along the "liver-brain" axis. Mechanistically, the neurotransmitters from the tryptophan metabolic pathway were converted to the toxic KYN pathway after BPF treatment. With the ELISA assay, it revealed that the toxic KYN metabolites, including KYN and 3-hydroxykynurenine (3-HK), were strikingly increased in the mouse brains which was ascribed to the enhanced expression of the rate-limiting enzymes Indoleamine 2,3-dioxygenase (IDO1) and Kynurenine 3-monooxygenase (KMO) respectively. Interestingly, the increased brain KYN induced by BPF was also validated partially from the periphery, since the ELISA and western blotting results indicated the significantly increased KYN in the serum and L-type amino acid transporter 1 (LAT1) in the brain, the key transporter responsible for KYN and 3-HK crossing the blood-brain barrier. Intriguingly, the liver-derived KYN metabolic pathway was the important source of the peripheral KYN and 3-HK, as BPF substantially enhanced hepatic IDO1, Tryptophan, 2, 3-dioxygenase (TDO2), and KMO levels indicated by western blotting. This study is the first to delineate previously unrecognized BPF-induced depression by regulating the KYN metabolic pathway along the "liver-brain" axis; therefore, targeting LAT1 or hepatic KYN signaling may provide a potentially unique therapeutic intervention in BPF-induced depression.

Mystery of bisphenol F-induced nonalcoholic fatty liver disease-like changes: Roles of Drp1-mediated abnormal mitochondrial fission in lipid droplet deposition.

As one of the major substitutes for bisphenol A (BPA), bisphenol F (BPF) has been widely used. Our previous study demonstrated that BPF exposure facilitates lipid droplet deposition in hepatic cells, contributing to nonalcoholic fatty liver disease (NAFLD)-like changes. However, the underlying mechanisms remain poorly understood. Here, with a metabolic cage system, we observed the perturbation of energy metabolism in mice treated with BPF. BPF obviously suppressed metabolic capacity, which manifested as decreased energy expenditure, low O2 consumption and CO2 levels in mice. Consistent with the in vivo results, a Seahorse XF Cell Mito Stress Test showed significant reductions in mitochondrial ATP production capacity, maximum respiratory capacity, and residual respiratory capacity after BPF treatment in an in vitro study. Electron microscopy revealed a striking increase in mitochondrial fission that was synchronous with excessive expression and activation of dynamin-related protein 1 (Drp1). Intriguingly, chemical inhibition of Drp1 by Mdivi-1 and/or silencing of Drp1 dramatically hampered mitochondrial fission and ameliorated BPF-induced lipid droplet deposition both in mouse liver and human hepatic cells. Mechanistically, mitochondrial dynamics imbalance played prominent roles in these processes, since suppression of Drp1 by chemical inhibition or knockdown substantially reversed BPF-induced mitochondrial fission and ameliorated the suppression of mitochondrial metabolism as well as excessive mitochondrial ROS, which was verified to be key to lipid droplet deposition. Collectively, the findings of the current study reveal previously unrecognized effects involving Drp1-mediated mitochondrial injury in BPF-induced lipid droplet deposition. Therefore, targeted intervention against mitochondrial dysfunction may be a promising therapeutic strategy for BPF-induced NAFLD-like changes.

Minimum local anesthetic dose of ropivacaine in real-time ultrasound-guided intraspinal anesthesia for lower extremity surgery: a randomized controlled trial.

BACKGROUND: Despite the many advantages real-time ultrasound-guided lumbar anesthesia has over traditional lumbar anesthesia, it seemingly involves a much higher dose of ropivacaine. This study aimed to determine the minimum local anesthetic dose (MLAD) and the 95% confidence interval of ropivacaine at different concentrations in real-time ultrasound-guided lumbar anesthesia for lower extremity surgery. METHODS: A total of 60 patients who were consecutively scheduled for selective lower extremity surgery were enrolled. The patients were randomly divided into two groups, which each received different concentrations of ropivacaine at different initial dosages when Dixon's up-and-down sequential method was applied. The high ropivacaine group and the low ropivacaine group received 0.75% and 0.5% ropivacaine, respectively. The patients' baseline characteristics, the MLAD, and the 95% confidence interval were assessed. The highest level of sensory block, time to reach the T10 sensory block, duration for sensory blocks higher than T10, highest plane for sensory block, and onset time and duration for motor block were recorded. Comparisons were also made between the patients' vital signs and adverse reactions. RESULTS: The minimum local anaesthetic dose (MLAD) and 95% confidence interval in the high ropivacaine group and the low ropivacaine group were 17.176 (16.276 to 18.124) and 20.192 (19.256 to 21.174) mg, respectively. Moreover, motor block maintenance was greatly reduced in the 0.5% ropivacaine compared to the 0.75% ropivacaine group (P=0.0309). CONCLUSIONS: In real-time ultrasound-guided intraspinal anesthesia for lower extremity surgery, both 0.75% and 0.5% ropivacaine provide satisfactory anesthesia. Our results suggest that shortened motor block duration can hold benefits for patients including earlier mobilization and a quicker rehabilitation process.

Radiomics for lung adenocarcinoma manifesting as pure ground-glass nodules: invasive prediction.

OBJECTIVES: To investigate the value of radiomics based on CT imaging in predicting invasive adenocarcinoma manifesting as pure ground-glass nodules (pGGNs). METHODS: This study enrolled 395 pGGNs with histopathology-confirmed benign nodules or adenocarcinoma. A total of 396 radiomic features were extracted from each labeled nodule. A Rad-score was constructed with the least absolute shrinkage and selection operator (LASSO) in the training set. Multivariate logistic regression analysis was conducted to establish the radiographic model and the combined radiographic-radiomics model. The predictive performance was validated by receiver operating characteristic (ROC) curve. Based on the multivariate logistic regression analysis, an individual prediction nomogram was developed and the clinical utility was assessed. RESULTS: Five radiomic features and four radiographic features were selected for predicting the invasive lesions. The combined radiographic-radiomics model (AUC 0.77; 95% CI, 0.69-0.86) performed better than the radiographic model (AUC 0.71; 95% CI, 0.62-0.81) and Rad-score (AUC 0.72; 95% CI, 0.63-0.81) in the validation set. The clinical utility of the individualized prediction nomogram developed using the Rad-score, margin, spiculation, and size was confirmed in the validation set. The decision curve analysis (DCA) indicated that using a model with Rad-score to predict the invasive lesion would be more beneficial than that without Rad-score and the clinical model. CONCLUSIONS: The proposed radiomics-based nomogram that incorporated the Rad-score, margin, spiculation, and size may be utilized as a noninvasive biomarker for the assessment of invasive prediction in patients with pGGNs. KEY POINTS: • CT-based radiomics analysis helps invasive prediction manifested as pGGNs. • The combined radiographic-radiomics model may be utilized as a noninvasive biomarker for predicting invasive lesion for pGGNs. • Radiomics-based individual nomogram may serve as a vital decision support tool to identify invasive pGGNs, obviating further workup and blind follow-up.

Use of contrast-enhanced computed tomographic imaging to diagnose and evaluate Behçet's disease with vascular complications.

In the present study, multi-slice CT results of patients with Behçet's disease (BD) and vascular complications were retrospectively evaluated. From January 2016 to May 2018, 45 of 361 patients with BD were diagnosed with vascular involvement. The clinical background, laboratory parameters and response to therapy of those patients were assessed. The following characteristics of vascular aneurysms were analyzed: Maximum diameter, length, wall thickness, borders, luminal changes, mural thrombus, cystic change of the vessel walls, asymmetric bulging of the right part of the aortic wall (RP type) and calcific plaques. The 45 BD patients analyzed included 37 males and 8 females with a median age of 40 years (30-49 years). Significant differences were observed among genders regarding age, ocular disorders and digestive-tract ulceration. A total of 42 aneurysms were identified with a mean diameter of 43 mm. Most aneurysmal walls (88%) were homogeneously enhanced on contrast-enhanced CT. Comparison of groups classified by aortic and larger arterial aneurysms indicated that aneurysms occurring in the aorta were more likely to form a mural thrombus, have a thicker wall (P<0.001) and unclear borders (P=0.036), to be of the RP type (P=0.003) and have a longer extension (P=0.001) compared with those in larger arteries. Unclear border of the aneurysmal wall was the only radiologic predictor correlated with an elevated erythrocyte sedimentation rate (P<0.001). In conclusion, characteristic CT imaging features of aneurysms may help to diagnose vascular involvement of BD and assess its severity, particularly in the absence of the classical clinical manifestations.

Magnetic Targeting Improves the Therapeutic Efficacy of Microbubble-Mediated Obstructive Thrombus Sonothrombolysis.

BACKGROUND: Magnetic targeting may help microbubbles (MBs) reach obstructive thrombi and improve the efficacy of MB-mediated sonothrombolysis, but the role of magnetic targeting in MB-mediated sonothrombolysis remains elusive. OBJECTIVES: We investigate the feasibility and efficacy of magnetically targeted MB-mediated sonothrombolysis for the treatment of obstructive thrombi. MATERIALS AND METHODS: Red and white thromboembolic models were established in vitro and in vivo. The models were randomly assigned to the control, ultrasound plus control MB (US + C-MB), ultrasound plus magnetic MB (US + M-MB), or US + M-MB + recombinant tissue-type plasminogen activator (r-tPA) groups and treated for 30 minutes. The recanalization rate, average blood flow velocity, hindlimb perfusion, and skeletal muscle injury marker levels were recorded. RESULTS: The recanalization rate, average blood flow velocity, and hindlimb perfusion in the red and white thromboembolic models were all significantly higher in the US + M-MB and US + M-MB + r-tPA groups than in the control and US + C-MB groups both in vitro and in vivo. Moreover, the levels of the skeletal muscle injury markers were all significantly lower in the US + M-MB and US + M-MB + r-tPA groups than in the other two groups in vivo for both thromboembolic models. However, the thrombolytic effects of red thrombi performed better than those of white thrombi in the US + M-MB + r-tPA group. CONCLUSION: M-MB-mediated sonothrombolysis improves the efficacy of thrombolysis both in vitro and in vivo, and reduces tissue damage in clogging model; thus, this method may serve as a promising approach for treating thrombus-occlusive diseases.

LncRNA H19 promotes vascular inflammation and abdominal aortic aneurysm formation by functioning as a competing endogenous RNA.

Abdominal aortic aneurysm (AAA) is accepted as a chronic vascular inflammatory disease. However, how the inflammatory response is regulated during AAA formation is not fully understood. This study was undertaken to determine whether the long noncoding RNA (lncRNA) H19 (H19) promotes AAA formation by enhancing aortic inflammation. qRT-PCR detected the upregulation of H19 in human and mouse AAA tissue samples. Co-staining for H19 and the macrophage marker MAC-2 showed that H19 was located in vascular smooth muscle cells (VSMCs) and infiltrating aortic macrophages. In vivo overexpression of H19 increased vascular inflammation and induced AAA formation, which was supported by exacerbated aortic morphology, maximum aortic diameter values, elastin degradation, expression of interleukin-6 (IL-6) and macrophage chemoattractant protein-1 (MCP-1), and macrophage infiltration. H19 suppression resulted in the opposite effects. A rescue experiment indicated that IL-6 neutralization significantly mitigated the aortic inflammation and AAA formation evoked by H19 overexpression. Luciferase reporter assays and ex vivo experiments using VSMCs and macrophages confirmed that H19 induced aneurysm formation in part via endogenous competition with the let-7a microRNA to induce the transcription of its target gene, IL-6. This mechanism was further validated by in vivo experiments using a mutant H19 that could not effectively bind let-7a. Collectively, our study revealed a pathogenic H19/let-7a/IL-6 inflammatory pathway in AAA formation, which offers a new potential therapeutic strategy for AAA.

3D Deep Learning from CT Scans Predicts Tumor Invasiveness of Subcentimeter Pulmonary Adenocarcinomas.

: Identification of early-stage pulmonary adenocarcinomas before surgery, especially in cases of subcentimeter cancers, would be clinically important and could provide guidance to clinical decision making. In this study, we developed a deep learning system based on 3D convolutional neural networks and multitask learning, which automatically predicts tumor invasiveness, together with 3D nodule segmentation masks. The system processes a 3D nodule-centered patch of preprocessed CT and learns a deep representation of a given nodule without the need for any additional information. A dataset of 651 nodules with manually segmented voxel-wise masks and pathological labels of atypical adenomatous hyperplasia (AAH), adenocarcinomas in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive pulmonary adenocarcinoma (IA) was used in this study. We trained and validated our deep learning system on 523 nodules and tested its performance on 128 nodules. An observer study with 2 groups of radiologists, 2 senior and 2 junior, was also investigated. We merged AAH and AIS into one single category AAH-AIS, comprising a 3-category classification in our study. The proposed deep learning system achieved better classification performance than the radiologists; in terms of 3-class weighted average F1 score, the model achieved 63.3% while the radiologists achieved 55.6%, 56.6%, 54.3%, and 51.0%, respectively. These results suggest that deep learning methods improve the yield of discriminative results and hold promise in the CADx application domain, which could help doctors work efficiently and facilitate the application of precision medicine. SIGNIFICANCE: Machine learning tools are beginning to be implemented for clinical applications. This study represents an important milestone for this emerging technology, which could improve therapy selection for patients with lung cancer.

Comparison of Magnetic Microbubbles and Dual-modified Microbubbles Targeted to P-selectin for Imaging of Acute Endothelial Inflammation in the Abdominal Aorta.

PURPOSE: Ultrasound molecular imaging (UMI) has potential to evaluate an inflammatory profile of endothelium. However, it is less successful in large arteries. This study compared magnetic microbubbles (MBs) selectively targeted to endothelial P-selectin and dual-targeting MBs in vitro and in vivo. PROCEDURES: MBs were modified with P-selectin antibody (MBPM) or isotype control antibody (MBCM) via a magnetic streptavidin bridge, and MBs were conjugated to P-selectin antibody (MBP) or both P-selectin antibody and PAA-sialyl Lewisx (MBD) via regular streptavidin linker. Adherence of MBs was determined by using a parallel plate flow chamber at variable shear stress (0.5-24 dyn/cm2). Adhesive and magnetic behaviors of MBs were analyzed at 4.0 dyn/cm2 or at a flow rate of 50 mm/s. Attachment of MBs to P-selectin was determined with contrast-enhanced ultrasound (CEU) imaging of murine abdominal aorta inflammation. The expression of P-selectin was assessed by immunohistochemistry. RESULTS: The adhesive efficacy of MBD was greater than MBP and MBCM, but lower than MBPM under all shear stress conditions (P < 0.05). The behaviors of fast-binding and rolling slow down were noted in MBD and MBPM; meanwhile, magnetic shifting of MBs centerline was presented in MBPM. Contrast video intensity (VI) from adhered MBPM to P-selectin of the inflammatory aorta was significantly higher than those from MBD and MBP (P < 0.05). CONCLUSIONS: MBPM may be a better molecular probe than MBD for detection of P-selectin on aorta with CEU, likely due to the shifting of axial distribution. Thus, it may improve the detection of the inflammatory profile on large arteries by UMI.

Protective effects of dexmedetomidine combined with flurbiprofen axetil on remifentanil-induced hyperalgesia: A randomized controlled trial.

High dosages of intra-operative remifentanil are associated with opioid-induced hyperalgesia (OIH). The aim of the present study was to investigate the effect of combined dexmedetomidine and flurbiprofen axetil treatment on remifentanil-induced hyperalgesia. Patients with an American Society of Anesthesiologists physical status of I-II who were diagnosed with hysteromyoma and scheduled for laparoscopic assisted vaginal hysterectomy (LAVH) were randomly divided into three groups. Group hyperalgesia (Group H, n=29) received intra-operative remifentanil, Group hyperalgesia and dexmedetomidine (Group HD, n=28) received remifentanil and a continuous infusion of dexmedetomidine, and Group hyperalgesia, dexmedetomidine and flurbiprofen axetil (Group HDF, n=29) received remifentanil, flurbiprofen axetil and dexmedetomidine. Mechanical pain thresholds were measured during the preoperative visit and postoperatively at 1, 6 and 24-h time points. Visual analog scale (VAS) scores, time to analgesic requirement, total sufentanil consumption and side effects were assessed postoperatively. Mechanical pain threshold at the incision site was significantly lower in Group H compared with Groups HD and HDF (both P<0.05), and significantly higher in Group HDF than in Group HD (P<0.05). The area of secondary hyperalgesia at the incision site was greater in Group H than in the other two groups (both P<0.05), and significantly smaller in Group HDF compared with Group HD (P<0.05). VAS scores and total sufentanil consumption were significantly higher in Group H compared with the other two groups (both P<0.05), and were significantly lower in Group HDF compared with Group HD (P<0.05). Dexmedetomidine combined with flurbiprofen axetil exhibits synergetic effects in the prevention of remifentanil-induced hyperalgesia in patients undergoing LAVH.

Dexmedetomidine Ameliorate CLP-Induced Rat Intestinal Injury via Inhibition of Inflammation.

The aim was to verify that dexmedetomidine (DEX) can attenuate CLP-induced intestinal injury via inhibition of inflammation. Male Sprague-Dawley (SD) rats were randomly allocated into Sham group and the other three CLP model groups, in terms of different treatments: placebo, DEX, and yohimbine plus DEX (DEX + YOH) groups. Pathology examination was conducted with HE stain. To identify differences among groups, the levels of DAO, and D-lactate in serum were measured by spectrophotometry, and the levels of TNF-α, IL-1ß, and IL-6 in serum and organ were measured by ELISA. The expressions of occludin and TLR4 in tissue were detected by Western blot. The survival rate of an additional group of animals within 7 d was recorded. In DEX group, mortality was lower, histology change was minor, DAO, and D-lactate levels were reduced, and occludin expression was increased; the expressions of TNF-α, IL-1ß, IL-6, and TLR4 were also decreased in DEX group. These results indicated that acute intestinal injury induced by CLP was mitigated by DEX treatment. However, these effects of DEX were significantly attenuated by yohimbine in DEX + YOH group. Our study indicated the protective effects of DEX on CLP-induced injury, which may be associated with the inhibition of inflammation via modulating TLR4 pathway and can be blocked by yohimbine.

Transcutaneous electric acupoint stimulation at Jiaji points reduce abdominal pain after colonoscopy: a randomized controlled trial.

BACKGROUND: Transcutaneous electric acupoint stimulation (TEAS) at Jiaji acupuncture points has therapeutic potential for relieving viscera pain and opioid-related side effects. This prospective, randomized, triple-blinded, placebo-controlled trial was to investigate the efficacy of TEAS on abdominal pain after colonoscopy. METHODS: Consecutive outpatients with American Society of Anesthesiologists (ASA) physical status I or II underwent selective colonoscopy were randomly assigned into two groups for either TEAS or sham pretreatment. The primary outcomes were the incidence of abdominal pain after colonoscopy. The secondary outcomes included the incidence of abdominal distension, postoperative nausea and vomiting (PONV), duration of PACU stay, and patient's satisfaction and acceptance. RESULTS: Among the 229 patients analyzed, fewer occurrence of post-procedural abdominal pain (11.4% vs 25.2%, P = 0.007) and distension (1.8% vs 7.8%, P = 0.032) were observed in TEAS group, when compared with the sham group. The duration of PACU stay was significant shortened in TEAS group (P < 0.001). Meanwhile, patients' satisfaction score to medical service was higher (P < 0.001), and their acceptance to colonoscopy was improved (P = 0.011). CONCLUSION: Pretreatment with TEAS can reduce post-procedural discomfort, provide more efficient medical resources utilization, and improved patient's satisfaction and colonoscopy acceptance.

Intranasal dexmedetomidine premedication reduces minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion and emergence delirium in children: a prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND: We conducted a prospective, randomized, double-blind, placebo-controlled study to verify the hypothesis that intranasal dexmedetomidine premedication can reduce the minimum alveolar concentration of sevoflurane for laryngeal mask airway insertion in children. METHODS: Ninety American Society of Anesthesiologists (ASA) physical status I subjects, aged 3-7 years, were randomized to three equal groups to receive saline (Group S), dexmedetomidine 1 µg · kg(-1) (Group D1 ), or dexmedetomidine 2 µg · kg(-1) (Group D2 ) approximately 45 min before anesthesia. The minimum alveolar concentration for laryngeal mask airway insertion of sevoflurane was determined according to the Dixon's up-and-down method. Emergence delirium was evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale in the postanesthesia care unit (PACU). RESULTS: Dexmedetomidine premedication of 1 and 2 µg · kg(-1) was associated with reduction in sevoflurane from 1.92% to 1.53% and 1.23%, corresponding to decrease of 20% and 36%, respectively. The peak PAED scores (median [IQR]) were 9 [8-11.5], 5 [3-5.3], and 3 [2-4] in Group S, Group D1, and Group D2 , respectively. The incidence of emergence delirium (defined as peak PAED score ≥ 10) was significantly lower in Groups D1 and D2 than in Group S (P < 0.001). Simultaneously, the induction qualities and the parent's satisfaction scores were significantly higher in Groups D1 and D2 than in Group S (P < 0.001). CONCLUSION: Intranasal dexmedetomidine premedication produces a dose-dependent decrease in the minimum alveolar concentration for laryngeal mask airway insertion of sevoflurane and emergence delirium in the PACU.

In vivo ultrasound molecular imaging of inflammatory thrombosis in arteries with cyclic Arg-Gly-Asp-modified microbubbles targeted to glycoprotein IIb/IIIa.

OBJECTIVE: Ultrasound molecular imaging has the potential to detect activated platelets, thus identifying atherosclerotic plaque instability before onset of serious clinical events. However, it has not been well defined in inflammatory arterial thrombosis. We hypothesized that microbubbles (MBs) target glycoprotein IIb/IIIa (GP IIb/IIIa) could achieve a noninvasive in vivo detection of inflammatory thrombosis in large arteries through contrast-enhanced ultrasound (CEU) imaging. MATERIALS AND METHODS: Lipid shell-based gas-filled MBs were modified covalently with a cyclic Arg-Gly-Asp (RGD) peptide (MB-cRGD) targeted to activated GP IIb/IIIa or a negative control peptide (MB-CON) via thiol-maleimide coupling. Adherence of MB-cRGD and MB-CON to GP IIb/IIIa was determined in vitro by using a parallel plate flow chamber at variable shear stress (0.5-8 dynes/cm2). Inflammatory platelet thrombosis was induced by periadvential application of arachidonic acid (AA) to one of the bilateral carotids of C57BL/6 mice (n = 20) and confirmed through intravital fluorescence microscopy. Attachment of MBs was determined in vivo with CEU imaging of bilateral carotids in the AA application mice with (n = 10) or without (n = 10) pretreatment of GP IIb/IIIa antagonist. The expression of integrin GP IIb/IIIa was assessed through immunohistochemistry. RESULTS: Microbubble-cRGD but not MB-CON had excellent affinity to GP IIb/IIIa under all shear stress conditions. Successful inflammatory platelet activation and thrombosis in AA application carotids were noted through intravital fluorescence microscopy. Contrast video intensity from adhered MB-cRGD in the thrombi was significantly higher than that from MB-CON (P < 0.05). Video intensity of MB-cRGD in the thrombi was suppressed significantly by preblocking with GP IIb/IIIa antagonist (P < 0.05) but not for MB-CON. Immunohistochemical finding demonstrates that expression of integrin GP IIb/IIIa in the thrombi was abundant; it was inhibited significantly through pretreatment with GP IIb/IIIa antagonist (P < 0.05). CONCLUSIONS: Cyclic RGD-modified MBs targeted to GP IIb/IIIa with CEU are capable of detecting inflammation-activated platelets and thrombosis in large arteries, thus providing a potential tool for identification of vulnerable atherosclerotic plaques.

3C3R modified PBL pediatric teaching of Chinese medical students.

A Content, Context, Connection and Researching, Reasoning, Reflecting (3C3R) model is a conceptual framework for problem-based learning (PBL) problem design. We introduced the 3C3R-PBL method into a pediatric teaching plan, and evaluated its effectiveness and feasibility. The 3C3R model was applied in a pediatric problem design teaching plan "why the lips turn purple when a baby is crying". All students were assigned either into a traditional PBL course or into a 9-step 3C3R model PBL course (3C3R-PBL). The performance outcomes of both groups were compared. For the PBL group, the proportion of students scoring ≥4 for content, context, and problem design connection, was 90.8%, 80.3%, and 64.5% respectively, while for tutors, it was 71.4%, 71.4%, and 28.6%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 81.6%, 55.3%, and 40.8%, while for tutors, it was 71.4%, 100%, and 57.1%. The learning difficulty was not considered high with only 31.6% of students and 42.9% of tutors rating the task as difficult. For the 3C3R-PBL group, the proportion of students scoring content, context, and connection, ≥4 was 100%, 98.4%, and 90.5%, while for tutors it was 100%, 100%, 83.3%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 95.2%, 88.9%, and 76.2%, while for tutors it was 100% for all 3 R components. Students and tutors were convinced by the content, case context, research process and reasoning process of both teaching plans, while scores for connection and reflecting were significantly improved when the PBL plan was amended by a 3C3R model (p<0.05) and the case learning difficulty was statistically increased (p<0.05). The 3C3R model, evaluated for the first time in China, was helpful for effective and reliable problem design in a pediatric PBL teaching plan for Chinese students.

Persistence of systolic and diastolic regional dysfunction after brief episodes of myocardial ischemia evaluated with velocity vector imaging.

BACKGROUND: The time course and characteristics of persistent regional dysfunction after ischemia remain unclear. Velocity vector imaging (VVI) allows accurate quantification of regional myocardial function. The aim of this study was to characterize the time course of regional diastolic and systolic abnormality after recovery from different durations of ischemia by VVI. METHODS: 72 rats underwent brief left coronary occlusion (3, 5, 10 and 15 min, respectively) followed by reperfusion for 4-8h. Hemodynamic measurements and VVI were performed at various time points. Regional systolic and diastolic functions were estimated from peak diastolic and systolic circumferential strain rate (SR-d and SR-s) of the left ventricle, respectively. RESULTS: Both SR-d and SR-s were significantly decreased in the ischemic segment during occlusion compared to non-ischemic segment. With the increase in occlusive time, the duration of reduced SR-d and SR-s after reperfusion was prolonged. Both SR-d and SR-s returned to pre-occlusion values in less than 30 min after reperfusion in the 3 min and 5 min ischemia groups. However, in the 10- and 15-min ischemia groups, SR-d did not fully recovered even at 240 min after reperfusion despite complete recovery of SR-s. The left ventricular hemodynamics during occlusion were significantly changed in all groups and returned to baseline immediately after reperfusion. CONCLUSION: The persistence of diastolic regional dysfunction is longer than systolic regional dysfunction after a relative longer ischemic event, suggesting that recent myocardial ischemic insult mimicking variant angina may be recognized with the evaluation of regional diastolic function.

[Effects of high and low shear stress on vascular remodeling and endothelial vascular cell adhesion molecular-1 expression in mouse abdominal aorta].

OBJECTIVE: To establish a mouse model of abdominal aorta stenosis and analyze the alterations in the arterial wall response to high and low shear stress. METHODS: Twenty mouse were randomized equally into 4 groups, including 3 test groups (1, 7 and 14 day groups) with surgically induced stenosis of the abdominal aorta, and a sham-operated group without stenosis. The hemodynamics and the internal diameter of the blood vessel were measured by color Doppler flow imaging. The wall shear stress was calculated by Poiseiulle hydrodynamics formula (τ(m)=η×4×V(m)/D). Pathological examination and immunohistochemistry were performed to observe the arterial morphological changes and the endothelial vascular cell adhesion molecule-1 (VCAM-1) expression. The intimal-media thickness of the aorta was measured and endothelial VCAM-1 expression analyzed quantitatively. RESULTS: Regions of low and high flow shear stress were created upstream from the stenosis and within the stenosis, respectively. Compared with the sham-operated group, the mice with aorta stenosis showed gradually increased vascular intimal-media thickness and VCAM-1 expression intensity in the upstream aorta, but not within the regions of the stenosis. CONCLUSION: Vascular remodeling may occur shortly after exposure to low shear stress, which plays a significant role in initiation and progression of the pathological process of atherosclerosis mediated by VCAM-1, whereas high shear stress may exert an anti-atherosclerotic effect.

[Expression of TGF-beta and hepatocyte growth factor in kidney tissues of children with primary focal segmental glomerular sclerosis].

OBJECTIVE: To study the expression of transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) in kidney tissues of children with primary focal segmental glomerular sclerosis (FSGS) and the possible role of the two growth factors in the development of FSGS. METHODS: Kidney specimens were obtained from 33 children with primary FSGS and 7 children with isolated haematuria but without FSGS (control group). Of the 33 children with primary FSGS, 6 children had no renal tubule interstitial pathological damage (Experimental I group) and 27 children had renal tubule interstitial pathological damage (Experimental II group). Expression of TGF-beta and HGF in kidney tissues was ascertained by the immunohistochemical method. RESULTS: TGF-beta and HGF were expressed in the three groups, but there were significant differences among the three groups. The expression of TGF-beta and HGF in the two experiment groups increased significantly compared with that in the control group. The Experimental II group had increased TGF-beta expression but a significantly decreased HGF expression compared with the Experimental I group. The index of tubule interstitial pathological changes was positively correlated with the TGF-beta expression (r=0.763, P<0.01), but negatively correlated with the HGF expression (r=-0.461, P<0.05) in the Experimental II group. There was a negative correlation between TGF-beta and HGF expression in children with primary FSGS (r=-0.425, P<0.05). CONCLUSIONS: The expression of TGF-beta and HGF in kidney tissues is increased in children with primary FSGS. TGF-beta might be a fibrogenic factor and HGF might be an anti-fibrotic factor in the kidney in primary FSGS.