Noninvasive prediction of lymph node metastasis in pancreatic cancer using an ultrasound-based clinicoradiomics machine learning model.

OBJECTIVES: This study was designed to explore and validate the value of different machine learning models based on ultrasound image-omics features in the preoperative diagnosis of lymph node metastasis in pancreatic cancer (PC). METHODS: This research involved 189 individuals diagnosed with PC confirmed by surgical pathology (training cohort: n = 151; test cohort: n = 38), including 50 cases of lymph node metastasis. Image-omics features were extracted from ultrasound images. After dimensionality reduction and screening, eight machine learning algorithms, including logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), random forest (RF), extra trees (ET), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to establish image-omics models to predict lymph node metastasis in PC. The best omics prediction model was selected through ROC curve analysis. Machine learning models were used to analyze clinical features and determine variables to establish a clinical model. A combined model was constructed by combining ultrasound image-omics and clinical features. Decision curve analysis (DCA) and a nomogram were used to evaluate the clinical application value of the model. RESULTS: A total of 1561 image-omics features were extracted from ultrasound images. 15 valuable image-omics features were determined by regularization, dimension reduction, and algorithm selection. In the image-omics model, the LR model showed higher prediction efficiency and robustness, with an area under the ROC curve (AUC) of 0.773 in the training set and an AUC of 0.850 in the test set. The clinical model constructed by the boundary of lesions in ultrasound images and the clinical feature CA199 (AUC = 0.875). The combined model had the best prediction performance, with an AUC of 0.872 in the training set and 0.918 in the test set. The combined model showed better clinical benefit according to DCA, and the nomogram score provided clinical prediction solutions. CONCLUSION: The combined model established with clinical features has good diagnostic ability and can be used to predict lymph node metastasis in patients with PC. It is expected to provide an effective noninvasive method for clinical decision-making, thereby improving the diagnosis and treatment of PC.

ARIP: A Tool for Precise Interatomic Contact Area and Volume Calculation in Proteins.

The interplay patterns of amino acid residues are pivotal in determining the tertiary structure and flexibility of proteins, which in turn are intricately linked to their functionality and interactions with other molecules. Here, we introduce ARIP, a novel tool designed to identify contact residues within proteins. ARIP employs a modified version of the dr_sasa algorithm and an atomic overlap weighted algorithm to directly calculate the contact area and volume between atoms based on their van der Waals radius. It also allows for the selection of solvent radii, recognizing that not every atom in proteins can interact with water molecules. The solvent parameters were derived from the analysis of approximately 5000 protein and nucleic acid structures with water molecules determined using X-ray crystallography. One advantage of the modified algorithm is its capability to analyze multiple models within a single PDB file, making it suitable for molecular dynamic capture. The contact volume is symmetrically distributed between the interacting atoms, providing more informative results than contact area for the analysis of intra- and intermolecular interactions and the development of scoring functions. Furthermore, ARIP has been applied to four distinct cases: capturing key residue-residue contacts in NMR structures of P4HB, protein-drug binding of CYP17A1, protein-DNA binding of SPI1, and molecular dynamic simulations of BRD4.

Myricetin exerts anti-biofilm activity and attenuates osteomyelitis by inhibiting the TLR2/MAPK pathway in experimental mice.

AIMS: To evaluate the potential of Myricetin against S.aureus induced osteomyelitis. BACKGROUND: Osteomyelitis is infected condition of bone by micro-organisms. The mitogen-activated protein kinase (MAPK), inflammatory cytokines and Toll-like receptor-2 (TLR-2) pathway are mainly involved in osteomyelitis. Myricetin is a plant-food derived flavonoid which shows anti-inflammatory activity. OBJECTIVE: In the present study, we evaluated the potential of Myricetin against S.aureus induced osteomyelitis. MC3T3-E1 cells were used for in vitro studies. METHOD: Murine model of osteomyelitis was developed in BALB/c mice by injecting S.aureus in the medullary cavity of the femur. The mice were studied for bone destruction, anti-biofilm activity, osteoblast growth markers alkaline phosphatase (ALP), osteopontin (OCN) and collagen type-I (COLL-1) were studied by RT-PCR, ELISA analysis for levels of proinflammatory factors CRP, IL-6 and IL-1ß. Expression of proteins by Western blot analysis and anti-biofilm effect by Sytox green dye fluorescence assay. Target confirmation was done by performing in silico docking analysis. RESULTS: Myricetin reduced bone destruction in osteomyelitis induced mice. The treatment decreased bone levels of ALP, OCN, COLL-1 and TLR2. Myricetin decreased serum levels of CRP, IL-6 and IL-1ß. The treatment suppressed activation of MAPK pathway and showed anti-biofilm effect. Docking studies suggested high binding affinity of Myricetin with MAPK protein in silico, by showing lower binding energies. CONCLUSION: Myricetin suppresses osteomyelitis by inhibiting ALP, OCN, COLL-1 via the TLR2 and MAPK pathway involving inhibition of biofilm formation. In silico studies suggested MAPK as potential binding protein for myricetin.

Secondary Hyperparathyroidism: Clinical Exploration of Endoscopic Total Parathyroidectomy Using the Oral Vestibular Approach with Forearm Autotransplantation.

Context: For secondary hyperparathyroidism (SHPT), physicians prefer conservative treatments, and surgical intervention has proven to be the best solution for some patients. Among the surgical interventions, total parathyroidectomy plus autotransplantation (TPTX+AT), using the forearm, is the major effective treatment. TPTX+AT, in conjunction with transoral endoscopic thyroidectomy vestibular approach (TOETVA), includes many advantages. Objective: The study intended to evaluate the clinical value of performing an endoscopic total parathyroidectomy TPTX+AT in conjunction with TOETVA in treating SHPT and to summarize and share the clinical experience. Design: The research team performed a prospective controlled study. Setting: The study took place at the Zhongshan Boai Hospital affiliated with Southern Medical University in Zhong Shan, Guangdong, China. Participants: Participants were 97 SHPT patients who were admitted to the hospital between March 2020 and March 2022. Intervention: The intervention group included 47 SHPT patients who received endoscopic TPTX+AT combined with the TOETVA, and the control group included 50 SHPT patients who received routine TPTX+AT. Outcome Measures: The research team performed comparisons between the groups regarding: (1) operating conditions, including intraoperative blood loss, operating time, and number of parathyroid glands detected intraoperatively; (2) clinical efficacy, (3) postoperative complications, (4) parathyroid hormone (PTH) and calcium (Ca) levels, (5) psychological status using the Hamilton Anxiety (HAMA) and the Hamilton Depression Scale (HAMD), and (9) life quality using the 36-Item Short Form Health Survey (SF-36). Results: The intervention group had significantly longer operation times and significantly greater intraoperative blood loss than the control group did, but the intervention group had fewer complications, lower PTH and Ca levels, and a higher efficacy (P < .05). The intervention group also had a significantly better psychological state and prognostic quality of life than the control group did (P < .05). Conclusions: Endoscopic treatment of SHPT using TPTX+AT in combination with TOETVA can significantly relieve clinical symptoms and lower serum PTH and Ca levels. The results suggest that the operation is safe and effective.

Ultrasound-based radiomics for predicting different pathological subtypes of epithelial ovarian cancer before surgery.

OBJECTIVE: To evaluate the value of ultrasound-based radiomics in the preoperative prediction of type I and type II epithelial ovarian cancer. METHODS: A total of 154 patients with epithelial ovarian cancer were enrolled retrospectively. There were 102 unilateral lesions and 52 bilateral lesions among a total of 206 lesions. The data for the 206 lesions were randomly divided into a training set (53 type I + 71 type II) and a test set (36 type I + 46 type II) by random sampling. ITK-SNAP software was used to manually outline the boundary of the tumor, that is, the region of interest, and 4976 features were extracted. The quantitative expression values of the radiomics features were normalized by the Z-score method, and the 7 features with the most differences were screened by using the Lasso regression tenfold cross-validation method. The radiomics model was established by logistic regression. The training set was used to construct the model, and the test set was used to evaluate the predictive efficiency of the model. On the basis of multifactor logistic regression analysis, combined with the radiomics score of each patient, a comprehensive prediction model was established, the nomogram was drawn, and the prediction effect was evaluated by analyzing the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve. RESULTS: The AUCs of the training set and test set in the radiomics model and comprehensive model were 0.817 and 0.731 and 0.982 and 0.886, respectively. The calibration curve showed that the two models were in good agreement. The clinical decision curve showed that both methods had good clinical practicability. CONCLUSION: The radiomics model based on ultrasound images has a good predictive effect for the preoperative differential diagnosis of type I and type II epithelial ovarian cancer. The comprehensive model has higher prediction efficiency.

Acute Respiratory Distress Syndrome Induced by White Smoke Inhalation: a Potential Animal Model For Evaluating Pathological Changes and Underlying Mechanisms.

BACKGROUND/AIMS: White smoke inhalation (WSI) is an uncommon but potentially deadly cause of acute respiratory distress syndrome (ARDS). However, no clinical treatment protocol has been established for the treatment of WSI-induced ARDS. Therefore, it is necessary to investigate the effects of WSI in ARDS and the mechanisms underlying the effects of WSI to determine a novel therapeutic target. METHODS: On the basis of the duration of continued inhalation of white smoke (3 min, 5 min, and 7 min), rats were divided into three groups (WSI-3 min, WSI-5 min, and WSI-7 min). The survival rate, pathological change, and computed tomography (CT) score were evaluated to determine the modeling conditions. In the established WSI-5 min models, evaluations were performed to evaluate the following: arterial blood gas levels, lung wet/dry weight ratio, the expression of inflammatory cytokines, and the effect of NF-κB signaling pathway. RESULTS: The survival rate of rats at 72 h post-WSI in the WSI-3 min, WSI-5 min, and WSI-7 min groups was 83.33%, 75%, and 25%, respectively. Results from evaluation of H&E staining, CT scan, arterial blood gas levels, and lung wet/dry weight ratio suggest that the pathological changes in the rat in the WSI-5 min and WSI-7 min groups are very similar to those in patients with ARDS induced by WSI. Additionally, the expression of INF-γ, TGF-ß1, TNF-α, and IL-1ß were increased, and the NF-κB signaling pathway was activated in the WSI-5 min group. CONCLUSION: The rat model of WSI-5 min can be used as a WSI-induced ALI model for further experiments. The NF-κB signaling pathway may be a potential therapeutic target for the treatment of WSI- induced ARDS.

Exercise Increases Cystathionine-γ-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats.

Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling.

Adenosine analogs as inhibitors of tyrosyl-tRNA synthetase: Design, synthesis and antibacterial evaluation.

Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 of 0.8±0.07 µM. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays.

Reduced expression of CRHR2 and Sp-1 in myocardium of ovariectomized rats is improved by exercise training.

Exercise training has been looked on as a non-pharmacologic approach to treating ovariectomy (OVX)-induced dysfunctions. In this study, we investigated whether chronic exercise impacts on expression of urocortins (UCNs) and corticotropin-releasing hormone receptor type 2 (CRHR2) in myocardium of OVX rats. Bilateral OVX or sham-operation was performed under anesthesia. Both groups were then divided into two subgroups, with or without treadmill training for 8 weeks. It was found that OVX as well as exercise did not affect the mRNA levels of UCN, UCN2 and UCN3 in myocardium. OVX caused down-regulation of CRHR2 in myocardium. Exercise training reversed the OVX-induced reduction of CRHR2, but had no influence on CRHR2 level in sham rats. OVX resulted in a decrease in estrogen receptor α (ERα) expression in myocardium, which was restored by exercise. Moreover, exercise training also reversed OVX-induced down-regulation of specific protein-1 (Sp-1) expression in myocardium. CRHR2 expression level correlated with Sp-1 and ERα level in myocardium. These results indicate that exercise training can restore the CRHR2 level in myocardium of OVX rats, which is associated with ERα and Sp-1 expression.

[Mechanism and influence of silencing TGM1 gene by siRNA on cell cycle distribution of keratinocytes].

OBJECTIVE: To explore the effects of cell cycle distribution and expression of cell cycle related proteins before and after transglutaminase 1 (TGM1) gene silencing by small interfering RNA (siRNA) in immortalized human keratinocytes (HaCaT cells). METHODS: Before and after RNA interference (RNAi) silencing TGM1 gene expression in HaCaT cells, the changes of cell cycle status were detected by flow cytometry. And the expressions of cell cycle related proteins cyclin D1, cyclin B1 and CDK4 were detected by immunocytochemistry and Western blot. RESULTS: After TGM1 silencing, the HaCaT cells increased in G(0)/G(1) phase (78.27% ± 1.83% vs 56.84 % ± 2.72% and 57.19% ± 3.72%, both P < 0.05) while decreased in S phases (32.78% ± 5.48% vs 57.32% ± 2.91% and 55.71 % ± 2.84%, both P < 0.05) and G(2)/M phases (3.66% ± 0.30% vs 9.39% ± 0.68% and 9.77% ± 0.52%, both P < 0.05) . Moreover, arrest of cell cycle was induced in S phase. After TGM1 silencing, cell proliferation was significantly inhibited while wild-type TGM1 displayed an accelerated growth rate. Inmmnohistochemistry indicated that cyclin D1, cyclin B1 and CDK4 had a strongly negative expression after transfecting with TGM1 siRNA. Western blot indicated that a very low endogenous expression of cyclin D1, cyclin B1 and CDK4 proteins was observed after transfecting with TGM1 siRNA. CONCLUSIONS: TGM1 siRNA may block the cell cycle of HaCaT cells. It suggests that TGM1 expression in HaCaT cells are closely related with cell cycle.

[Total trans-oral endoscopic thyroidectomy and cervical lymphadenectomy: a human cadavers surgery study].

OBJECTIVE: To find an approach for trans-oral endoscopic thyroidectomy (TOET) and cervical lymphadenectomy using conventional endoscopic surgical instruments on frozen fresh cadavers. METHODS: Six frozen fresh cadavers were used in three groups of trans-oral trocar installation experiments: oral vestibule installation, sublingual region installation, and combined bi-vestibular and sublingual installation. TOET (with pretrachealis method to thyroid fixation removal) and cervical lymphadenectomy were performed experiments on another 6 frozen fresh cadavers using the best access approach found in the aforementioned experiments. RESULTS: In oral vestibule trocar installations, the trocars caused large lacerated wound and damaged air tightness. In sublingual installations, only one trocar could be installed in the sublingual area because the space in sublingual area was limited. In combined bi-vestibular and sublingual installations, no gland, vessel or nerve was damaged. Combined bi-vestibular and sublingual access were selected as the surgical approach on the basic of analysis the merits of each approach. TOET and cervical lymphadenectomy in area III, IV, VI, VII were performed without making any accessory damage through combined bi-vestibular and sublingual access approach. CONCLUSIONS: TOET is feasible. Combined bi-vestibular and sublingual approach is available for TOET. Part of the cervical lymph nodes could be resected. Pretrachealis approach to thyroid fixation removal can still be used.

Performance of current versus modified CEUS LI-RADS in the diagnosis of non-hepatocellular carcinoma malignancies.

PURPOSE: The high proportion of HCC in CEUS LR-M decreases the sensitivity of LR-5 for the diagnosis of HCC. However, when modifying LR-M criteria to further improve the sensitivity of LR-5, it is also important not to compromise the diagnostic performance (especially sensitivity) of LR-M for non-hepatocellular carcinoma malignancies (non-HCCMs). The purpose of this study was to evaluate the diagnostic performance of CEUS LI-RADS (2017 version) for non-HCCMs and to explore the impact of modified CEUS LI-RADS on the diagnostic performance of LR-M. METHODS: In this retrospective study, patients with pathologically confirmed non-HCCMs were evaluated. Two radiologists independently interpreted the major CEUS features and categorized the liver lesions. New LR-M criteria were applied: early washout (< 45 s) or marked washout (< 5 min). The sensitivity values of the current and modified CEUS LR-M were assessed and then compared using a paired χ2 test. Cohen's κ was used to compare the inter-reader agreement of the LI-RADS categories. RESULTS: A total of 131 non-HCCMs were ultimately selected, including 71 intrahepatic cholangiocarcinomas, 26 combined hepatocellular cholangiocarcinomas, 29 metastases, and 5 other non-HCCMs. The numbers of LR-M, LR-5, LR-4, and LR-3 in liver lesions were 111, 18, 1, and 1, respectively. The inter-reader agreement of the LI-RADS categories for non-HCCMs was 0.59. The sensitivity of the current CEUS LR-M in diagnosing non-HCCMs was 84.7%. By adjusting the early washout time to < 45 s, the sensitivity of LR-M was 80.9%. By adjusting the marked washout time within 5 min, the sensitivity of LR-M was 72.5%. CONCLUSION: CEUS LR-M has high sensitivity in diagnosing non-HCCMs. For LR-M nodules with nonrim arterial phase hyperenhancement and early washout, advancing the time of early washout to < 45 s has a minimal impact on the sensitivity of LR-M in diagnosing non-HCCMs compared to the condition of increasing the marked washout within 5 min.

Acute Thyrotoxic Myopathy Combined with Neck Pain: A Case Report.

INTRODUCTION: Acute thyrotoxic myopathy (ATM) is a rare and potentially lethal complication of thyrotoxicosis. The typical clinical symptoms of ATM are characterized by bulbar paralysis. Reports of the successful treatment of ATM are sporadic due to its low incidence. However, no English literature has reported Chinese patients with ATM and neck pain. Here, we report for the first time a Chinese patient with ATM and neck pain who recovered through large doses of systemic glucocorticoids and one intrathyroidal steroid injection. CASE REPORT: A 23-year-old woman visited our hospital with a two-year history of progressive weakness of her bulbar muscles, hoarseness, cough when swallowing, dysphagia, and a one-month history of recurrent painful swelling of the thyroid gland. She was diagnosed with ATM, chronic thyrotoxic myopathy (CTM), and Graves' ophthalmopathy (GO) due to Graves' disease (GD). After she was treated with a combination of low-dose glucocorticoids, antithyroid drugs (ATDs), propranolol, and ultrasound-guided percutaneous intrathyroidal injection of glucocorticoids, her bulbar paralysis, proximal myopathy, and neck pain simultaneously improved without recurrence during follow-up. To our knowledge, this is the first case report of a patient with ATM, CTM, GD, GO and neck pain treated by administering a combination of low-dose glucocorticoids, one intrathyroidal steroid injection and antithyroid agents. CONCLUSIONS: Clinicians should consider ATM and intervene with aggressive glucocorticoid therapy, and this is the key to reversing the progression of ATM when a patient has bulbar paralysis and thyrotoxic symptoms. Our case report references the clinical diagnosis and treatment of such cases.

Ultrasound measurement of vastus lateralis and vastus medialis muscle parameters to identify chronic thyrotoxic myopathy.

Introduction: Chronic thyrotoxic myopathy (CTM) is a common, easily neglected complication of hyperthyroidism. There are currently no standard diagnostic criteria for CTM, and the ultrasonic characteristics of CTM-affected skeletal muscle remain unclear. Herein, we aimed to evaluate hyperthyroid patients for CTM by ultrasound and identify ultrasonic muscle parameter cutoffs for CTM diagnosis. Materials and methods: Each participant underwent ultrasonography. The original (muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA)) and corrected (MT/height (HT), MT/body mass index (BMI), CSA/HT, and CSA/BMI) parameters of the vastus lateralis and vastus medialis (VM) were evaluated. The diagnostic effectiveness of ultrasound for predicting CTM was determined using receiver operating characteristic (ROC) curve analysis. Our study included 203 participants: 67 CTM patients (18 males, 49 females), 67 non-CTM patients (28 males, 39 females) and 69 healthy controls (20 males, 49 females). Results: The CTM group had lower muscular ultrasonic and anthropometric parameters, higher thyroid hormone and thyroid-stimulating hormone receptor antibody (TRAb) levels, and a longer duration of hyperthyroidism than the non-CTM group (P < 0.05). The VM-PA, VM-CSA, VM-CSA/HT, and VM-CSA/BMI were lower in females than in males (P < 0.05). Free thyroxine (FT4) and TRAb both showed significant negative correlations with VM-MT, VM-MT/HT, VM-CSA, and VM-CSA/HT (P < 0.05). VM-MT/BMI and VM-CSA/HT, respectively, best predicted male and female CTM (AUC = 0.84, 0.85; cutoff ≤ 0.07, < 4.01). Conclusion: Ultrasound measurement of muscular parameters, especially in the VM, is a valid and feasible way of diagnosing and characterizing possible CTM in hyperthyroidism.

Experimental Study of Yield Surface in Polypropylene Considering Rate Effect: Stress Path Dependence.

In order to investigate the yield surface evolution of polypropylene (PP) under dynamic impact and the relationship between yield surface parameters and the strain rate, five shear-compression specimens (SCSs) with different inclination angles are designed and produced to explore the yield behavior of PP under dynamic loading. Dynamic combined stress loading paths with different compression-shear ratios are achieved by the split Hopkinson pressure bar (SHPB). The evolution laws of the compressive stress and shear stress in the measurement region during the PP SCS compressive deformation process are analyzed. In terms of mechanical response, PP under combined compression-shear loading is of visco-elasticity plasticity and its deformation undergoes a three-stage transition, namely "unyield→yield→failure". The yield characteristics of PP are found to be affected not only by the hydrostatic pressure but also by the stress path. According to the Hu-Pae yield criterion, the dynamic yield surface and model parameters of PP are obtained, and the relationship between the yield surface and the strain rate is ascertained. These findings contribute to deepening the research on the mechanical response characteristics of PP-based materials.

In vitro and vivo study of tranilast protects from acute respiratory distress syndrome and early pulmonary fibrosis induced by smoke inhalation.

BACKGROUND: Tranilast (N-[3＇,4＇-dimethoxycinnamoyl]-anthranilic acid) is an analog of a tryptophan metabolite. It was identified with anti-inflammatory and antifibrotic activities, and used in the treatment of a variety of diseases, such as anti - allergy, bronchial asthma, and hypertrophic scars. As a drug with few adverse reactions, tranilast has attracted great attention, but its application is limited due to the uncertainty of dosages and mechanisms. In this study, the protection effects of different doses of tranilast on smoke inhalation mediated lung injury on rats, and on the damage of three kinds of lung cells in vitro were investigated. METHOD: In vivo, Sprague-Dawley rats were randomly divided into sham group, smoke group (rats were exposed to pine sawdust smoke three times, each time for 5 min), different doses of tranilast treatment group (doses were 100 mg/kg, 200 mg/kg and 300 mg/kg, ip.) and placebo group. After 1, 3 and 7 days, pulmonary function, pathologic injury by HE staining, cytokines and oxidative stress level by kits were determined. At 7days, lung fibrosis was assessed by Masson's trichrome staining and the level of hydroxyproline (HYP). In vitro, three kinds of lung cells from normal rats were isolated: type II alveolar epithelial cells (AT-II), pulmonary microvascular endothelial cells (PMVECs) and pulmonary fibroblasts (PFs). To investigate the potential effects of tranilast on cell proliferation, cell cycle and cytokine production of three kinds of lung cells exposed to smoke. RESULTS: Compared with smoke group and placebo group, tranilast treatment significantly reduced histopathological changes (such as pulmonary hemorrhage, edema and inflammatory cell infiltration, etc.), significantly reduced histopathological score (p < 0.05), increased arterial oxygen partial pressure, and decreased the levels of IL-1ß, TNF-α, TGF-ß1 (p < 0.05), oxidative stress and the expression of nuclear transcription factor κB (NF-κB) smoke exposed rats (p < 0.01). In particular, the effect of 200 mg/kg dose was more prominent. In vitro, smoke induced AT-II and PMVECs apoptosis, improved PFs proliferation (p < 0.01), activity of SOD and decreased the content of MDA (p < 0.01). However, tranilast seems to be turning this trend well. The inflammatory factor IL-11ß, TNF-α and TGF-ß1, and the expression of NF-κB were significantly lower in the tranilast treatment than in the smoke group (p < 0.01). CONCLUSION: This study indicates that tranilast had a protective effect on acute respiratory distress syndrome and early pulmonary fibrosis of rats in vivo. In addition, tranilast promotes proliferation of AT-II and PMVECs but inhibits PFs proliferation, down-regulates secretion of inflammatory cytokines and alleviates oxidative stress of AT-II, PMVECs and PFs after smoke stimuli in vitro.

The Mechanism and Experimental Validation of Forsythoside A in the Treatment of Male Infertility Were Analyzed Based on Network Pharmacology and Molecular Docking.

Chinese medicine extracts are currently the hotspot of new drug research and development. Herein, we report the mechanism of action of the traditional Chinese medicine extract Forsythiaside A in the treatment of male infertility and experimental verification. We first obtained 95 intersection genes between the target protein of Forsythiaside A and the target genes of male infertility and screened 13 key genes. In molecular docking, Forsythiaside A can each have a higher total docking score with 12 key genes and have a better combination. These 95 intersection genes are mainly related to biological processes such as response to peptide hormone, response to oxidative stress, and participation in the oxidative stress of the forkhead box O (FoxO) signaling pathway. Therefore, we use ornidazole to induce an experimental model of oligoasthenospermia in rats and use different concentrations of Forsythiaside A to intervene. We proved that the semen quality and superoxide dismutase (SOD) activities of model group rats were significantly lower than those of the blank group, and semen quality and SOD activities of the low-dose group and high-dose group were significantly higher than those of the model group. The malondialdehyde (MDA) level of model group rats was significantly higher than that of blank group, while the MDA levels of the low-dose group and high-dose group were significantly lower than that of the model group. Forsythoside A is a potential drug substance for male infertility and improves the semen quality, MDA levels, and SOD activities of rats with oligoasthenospermia.

Diagnostic performance and interreader agreement of CEUS LI-RADS in ≤ 30 mm liver nodules with different experienced radiologists.

PURPOSE: To explore the diagnostic performance and interreader agreement of CEUS LI-RADS in diagnosing ≤ 30 mm liver nodules with different experienced radiologists. METHODS: Between January 2018 and October 2020, 244 patients at high-risk for HCC who underwent CEUS were enrolled. Two novice radiologists and two expert radiologists independently evaluated LI-RADS categories and main features. Kappa (κ) and Kendall's tests were employed to evaluate the interreader agreement of CEUS LI-RADS. The diagnostic performance was determined based on sensitivity, specificity, accuracy, PPV and NPV. RESULTS: The interreader agreement for arterial phase hyperenhancement, late and mild washout, early washout, and rim hyperenhancement was moderate to almost perfect (κ, 0.44-0.93) among the different levels of radiologists. The interreader agreement for the LI-RADS categories was substantial to almost perfect (κ, 0.78-0.88). However, the interreader agreement for marked washout was fair to moderate (κ, 0.28-0.50). When CEUS LR-5 was used as a diagnostic criterion for HCC, there were no statistical differences in sensitivity, specificity, accuracy, PPV and NPV among the radiologists (p > 0.05), except for the differences between Reader 4 and the remaining three radiologists in terms of accuracy and sensitivity (p < 0.05). CONCLUSION: CEUS LI-RADS has good diagnostic agreement for ≤ 30 mm liver nodules among experienced radiologists.

In Situ Silver-Based Electrochemical Oncolytic Bioreactor.

In this study, it is shown for the first time that a reduced graphene oxide (rGO) carrier has a 20-fold higher catalysis rate than graphene oxide in Ag+ reduction. Based on this, a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which switched Ag+ prodrugs into in situ therapeutic silver nanoparticles with and above 95% transition rate is constructed to inhibit the growths of various tumors. In this SEOB-enabled intratumoral nanosynthetic medicine, intratumoral H2 O2 and rGO act as the reductant and the catalyst, respectively. Chelation of aptamers to the SEOB-unlocked prodrugs increases the production of silver nanoparticles in tumor cells, especially in the presence of Vitamin C, which is broken down in tumor cells to supply massive amounts of H2 O2 . Consequently, apoptosis and pyroptosis are induced to cooperatively contribute to the considerably-elevated anti-tumor effects on subcutaneous HepG2 and A549 tumors and orthotopic implanted HepG2 tumors in livers of nude mice. The specific aptamer targeting and intratumoral silver nanoparticle production guarantee excellent biosafety since it fails to elicit tissue damages in monkeys, which greatly increases the clinical translation potential of the SEOB system.

[Surgical anatomy of totally trans-oral video-assisted thyroidectomy].

OBJECTIVE: To define the anatomical approach, anatomical planes and related vessels and nerves to create a safe and reproducible combined sublingual and bi-vestibular access for trans-oral video-assisted thyroidectomy. METHODS: From November 2009 to May 2011, twenty-five embalmed human specimens were dissected for anatomical information of the cervical region, the mandible region and the supra-hyoid muscles. On twenty fresh frozen human specimens after an experimental trans-oral endoscopic thyroidectomy, the related vascular, neural structures and muscles were evaluated. RESULTS: The optical access port was placed in the midline sublingual. The geniohyoid muscle, mylohyoid muscle and the anterior belly of the digastric muscle were divided in the midline in order to reach the plane under the platysma muscle. The mucosa was sagittal incised bilaterally in the vestibular of oral cavity for working trocar, at the level of the first molar of the mandible. The working trocar reached directly the periosteum of the mandible, under the facial vessel and the marginal branch of facial nerve, and then passed below the platysma muscle into the infra-laryngeal working area. The distance from mental nerve to mandibular midline and between mental nerve and facial artery were (25.8 ± 0.9) mm and (29.4 ± 0.9) mm respectively. Anatomical dissections showed that after an experimental trans-oral combined sublingual and bi-vestibular access, all muscles of the floor of the oral cavity as well as the related vascular and neural structures are intact. The maximum nodule size of the resected specimens in the totally trans-oral approach was up to 50 mm. CONCLUSION: The combined sublingual and bi-vestibular access of trans-oral video-assisted thyroidectomy is safe and reproducible.