MRI-based radiomics assessment of the imminent new vertebral fracture after vertebral augmentation.

BACKGROUND: Imminent new vertebral fracture (NVF) is highly prevalent after vertebral augmentation (VA). An accurate assessment of the imminent risk of NVF could help to develop prompt treatment strategies. PURPOSE: To develop and validate predictive models that integrated the radiomic features and clinical risk factors based on machine learning algorithms to evaluate the imminent risk of NVF. MATERIALS AND METHODS: In this retrospective study, a total of 168 patients with painful osteoporotic vertebral compression fractures treated with VA were evaluated. Radiomic features of L1 vertebrae based on lumbar T2-weighted images were obtained. Univariate and LASSO-regression analyses were applied to select the optimal features and construct radiomic signature. The radiomic signature and clinical signature were integrated to develop a predictive model by using machine learning algorithms including LR, RF, SVM, and XGBoost. Receiver operating characteristic curve and calibration curve analyses were used to evaluate the predictive performance of the models. RESULTS: The radiomic-XGBoost model with the highest AUC of 0.93 of the training cohort and 0.9 of the test cohort among the machine learning algorithms. The combined-XGBoost model with the best performance with an AUC of 0.9 in the training cohort and 0.9 in the test cohort. The radiomic-XGBoost model and combined-XGBoost model achieved better performance to assess the imminent risk of NVF than that of the clinical risk factors alone (p < 0.05). CONCLUSION: Radiomic and machine learning modeling based on T2W images of preoperative lumbar MRI had an excellent ability to evaluate the imminent risk of NVF after VA.

Selenomethionine attenuates ochratoxin A-induced small intestinal injury in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation.

The aim of this study was to investigate whether selenomethionine (SeMet) could attenuate intestinal injury in rabbits induced by ochratoxin A (OTA). Sixty 35-day-old IRA rabbits with similar weights were randomly assigned to the control group, OTA group (0.2 mg OTA/kg b.w), OTA+ 0.2 mg/kg Se (0.2 mg OTA/kg b.w + 0.2 mg SeMet/kg feed), OTA+ 0.4 mg/kg Se (0.2 mg OTA/kg b.w + 0.4 mg SeMet/kg feed) and OTA+ 0.6 mg/kg Se (0.2 mg OTA/kg b.w + 0.6 mg SeMet/kg feed). The rabbits were examined after oral administration of different doses of SeMet for 21 days and were intragastrically administered OTA for 7 consecutive days. The results showed that pretreatment with different doses of SeMet protected against the changes in serum biochemical indicators and the decline in production performance caused by OTA exposure. In addition, the activities of SOD, GSH-PX and T-AOC were significantly increased, and the levels of MDA and ROS were decreased after SeMet pretreatment; thus, oxidative damage in rabbit jejunum tissue due to OTA exposure was inhibited. SeMet stimulates Nrf2 and inhibits the NF-κB signalling pathway; the anti-inflammatory response and antioxidative stress in rabbits were improved, and the intestinal barrier damage caused by OTA exposure was improved. In summary, SeMet alleviates OTA-induced intestinal toxicity in rabbits by activating the Nrf2 pathway and inhibiting NF-κB activation. Moreover, 0.4 mg/kg SeMet induced the most significant improvement.

[Identifying Depressive Disorder With Sleep Electroencephalogram Data: A Study Based on Deep Learning].

Objective: To explore the effectiveness of using deep learning network combined Vision Transformer (ViT) and Transformer to identify patients with depressive disorder on the basis of their sleep electroencephalogram (EEG) signals. Methods: The sleep EEG signals of 28 patients with depressive disorder and 37 normal controls were preprocessed. Then, the signals were converted into image format and the feature information on frequency domain and spatial domain was retained. After that, the images were transmitted to the ViT-Transformer coding network for deep learning of the EEG signal characteristics of the rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep in patients with depressive disorder and those in normal controls, respectively, and to identify patients with depressive disorder. Results: Based on the ViT-Transformer network, after examining different EEG frequencies, we found that the combination of delta, theta, and beta waves produced better results in identifying depressive disorder. Among the different EEG frequencies, EEG signal features of delta-theta-beta combination waves in REM sleep achieved 92.8% accuracy and 93.8% precision for identifying depression, with the recall rate of patients with depression being 84.7%, and the F0.5 value being 0.917±0.074. When using the delta-theta-beta combination EEG signal features in NREM sleep to identify depressive disorder, the accuracy was 91.7%, the precision was 90.8%, the recall rate was 85.2%, and the F0.5 value was 0.914±0.062. In addition, through visualization of the sleep EEG of different sleep stages for the whole night, it was found that classification errors usually occurred during transition to a different sleep stage. Conclusion: Using the deep learning ViT-Transformer network, we found that the EEG signal features in REM sleep based on delta-theta-beta combination waves showed better effect in identifying depressive disorder.

Acute Elevated Resistin Exacerbates Mitochondrial Damage and Aggravates Liver Steatosis Through AMPK/PGC-1α Signaling Pathway in Male NAFLD Mice.

Resistin was identified as a link between obesity and insulin resistance and is associated with many diseases in mice. Deciphering the related development and molecular mechanism is necessary for the treatment of these diseases. Previous studies have revealed that increased resistin levels are correlated with lipid accumulation and play a role in non-alcoholic fatty liver disease (NAFLD) development. However, the exact mechanisms underlying these processes remain unclear. To further clarify whether acute elevated resistin level exacerbated liver steatosis, a high-fat diet-induced NAFLD animal model was used and treated with or without resistin for 6 days. We discovered that resistin altered mitochondrial morphology, decreased mitochondrial content, and increased lipid accumulation in HFD mice. qRT-PCR and western blot analysis showed that acute elevated resistin significantly altered the gene expression of mitochondrial biogenesis and liver lipid metabolism molecules in HFD mice. Consequently, in vitro experiments verified that resistin reduced the mitochondrial content, impaired the mitochondrial function and increased the lipid accumulation of palmitate-treated HepG2 cells. Additionally, we demonstrated that resistin upregulated proinflammatory factors, which confirmed that resistin promoted the development of inflammation in NAFLD mice and palmitate-treated HepG2 cells. Signaling-transduction analysis demonstrated that acute elevated resistin aggravated liver steatosis through AMPK/PGC-1α pathway in male mice. This reveals a novel pathway through which lipogenesis is induced by resistin and suggests that maintaining mitochondrial homeostasis may be key to treatments for preventing resistin-induced NAFLD aggravation.

[Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism].

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Development of galangal essential oil-based microemulsion gel for transdermal delivery of flurbiprofen: simultaneous permeability evaluation of flurbiprofen and 1,8-cineole.

Flurbiprofen (FP) is one of the most potent nonsteroidal anti-inflammatory drugs with very low bioavailability of approximately 12% following transdermal administration, compared to that after oral administration. This study aimed to deliver FP as a microemulsion (ME) gel by transdermal administration. Galangal essential oil (GEO) was extracted from Rhizoma Alpiniae Officinarum and identified by GC-MS. The most abundant constituent was determined to be 1,8-cineole (52.06%). Compared to azone, GEO was proved to exert significantly higher (p < .01) penetration enhancement effect and significantly (p < .001) lower skin cell toxicity. The formulation (FP-GEO-ME gel) was prepared using GEO as an oil phase and a penetration enhancer. Compared to that of FP solution, the enhancement ratio (ER) of FP-GEO-ME gel was 4.06. In addition, more than 25% 1,8-cineole permeated through the rat skin. In vivo pharmacokinetic studies revealed that the AUC0-t of FP after transdermal administration of FP-GEO-ME gel was higher by approximately 4.56-fold than that of marketed FP cataplasms. The relative bioavailability of FP and 1,8-cineole after transdermal administration compared to oral administration of FP-GEO-ME were determined to be 96.58% and 85.49%, respectively. FP-GEO-ME gel significantly inhibited carrageenan-induced hind-paw edema and decreased PGE2 levels in rat serum. GEO-ME gel also exhibited significant anti-inflammatory effects at 2 h after the therapy (p < .05). The synergistic effects of FP and GEO were expected for the application of FP-GEO-ME gel. In conclusion, GEO-ME gel may be a promising formulation for transdermal administration of anti-inflammatory hydrophobic drugs, such as FP.

Identification of COVID-19 samples from chest X-Ray images using deep learning: A comparison of transfer learning approaches.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) constitutes a public health emergency globally. The number of infected people and deaths are proliferating every day, which is putting tremendous pressure on our social and healthcare system. Rapid detection of COVID-19 cases is a significant step to fight against this virus as well as release pressure off the healthcare system. OBJECTIVE: One of the critical factors behind the rapid spread of COVID-19 pandemic is a lengthy clinical testing time. The imaging tool, such as Chest X-ray (CXR), can speed up the identification process. Therefore, our objective is to develop an automated CAD system for the detection of COVID-19 samples from healthy and pneumonia cases using CXR images. METHODS: Due to the scarcity of the COVID-19 benchmark dataset, we have employed deep transfer learning techniques, where we examined 15 different pre-trained CNN models to find the most suitable one for this task. RESULTS: A total of 860 images (260 COVID-19 cases, 300 healthy and 300 pneumonia cases) have been employed to investigate the performance of the proposed algorithm, where 70% images of each class are accepted for training, 15% is used for validation, and rest is for testing. It is observed that the VGG19 obtains the highest classification accuracy of 89.3% with an average precision, recall, and F1 score of 0.90, 0.89, 0.90, respectively. CONCLUSION: This study demonstrates the effectiveness of deep transfer learning techniques for the identification of COVID-19 cases using CXR images.

Mitofusin2, a rising star in acute-on-chronic liver failure, triggers macroautophagy via the mTOR signalling pathway.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome with poor prognosis. Several studies have begun to prove that mitochondria play a crucial role in liver failure. Mitofusin2 (Mfn2) plays a key role in maintaining the integrity of mitochondrial morphology and function. However, the role and underlying mechanisms of Mfn2 on cell autophagy of ACLF remain unclear. Our aim was to explore the effect of Mfn2 on several biological functions involving cell autophagy in ACLF. In this study, we constructed an ACLF animal model and a hepatocyte autophagy model, using adenovirus and lentivirus to deliver Mfn2 to liver cells, in order to assess the effect of Mfn2 on autophagy and apoptosis in ACLF. Furthermore, we explored the biological mechanism of Mfn2-induced autophagy of ACLF using Western blotting, RT-PCR and electron microscopy. We found that Mfn2 significantly attenuated ACLF, characterized by ameliorated gross appearance and microscopic histopathology of liver, and reduced serum AST, ALT, and TBIL levels. Mfn2 improved the expressions of LC3-II, Atg5 and Bcl-2 and down-regulated the expression of P62 and Bax in ACLF. Like rapamycin, Mfn2 also significantly inhibited the expressions of p-PI3K, p-Akt and p-mTOR in ACLF. In conclusion, our findings suggest that Mfn2 influences multiple biological functions of ACLF via the PI3K/Akt/mTOR signalling pathway. This study will provide a reliable theoretical basis for the application of Mfn2 as an effective target for ACLF treatment, reversing or delaying the process of ACLF.

Integrated mRNA-Seq and miRNA-Seq analysis of PLCγ2-overexpressing hepatocarcinoma cells and identification of the associated miRNA-mRNA network.

Our previous study has discovered the positive effect of phospholipase Cγ 2 (PLCγ2) on the growth of hepatocarcinoma cells; however, the underlying mechanism is far from being understood. For this reason, this study attempts to identify the differently expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) in PLCγ2-overexpressing hepatocarcinoma cells. The results showed that totally 596 differently-expressed genes (DEGs) were identified in PLCγ2-expressed cells, including 314 upregulated and 282 downregulated ones; according to gene ontology analysis, these DEGs were involved in different cellular processes. Concurrently, 34 differently-expressed miRNAs (DEMs) were also detected in PLCγ2-expressing hepatocarcinoma cells. Moreover, the integrative analysis of miRNA and mRNA expression profiles identified the potential regulatory network linked to hepatocarcinoma-related biological processes, including metabolic activity, gene expression, cell cycle, cell migration, and so on. To our knowledge, it is the first study on the effect of PLCγ2 on miRNA and mRNA expressions in hepatocarcinoma cells, and the findings provide new insights into the mechanism supporting the growth-promoting effect of PLCγ2 in hepatocarcinoma cells.

Skin Electrical Resistance Measurement of Oxygen-Containing Terpenes as Penetration Enhancers: Role of Stratum Corneum Lipids.

The measurement of skin electrical resistance (SER) has drawn a great deal of attention for the rapid screening of transdermal penetration enhancers (PEs). However, the mechanisms underlying the SER measurement are still unclear. This study was to investigate the effects and mechanisms of seven oxygen-containing terpenes on the SER kinetics. Stratum corneum (SC) lipids were proved to play a key role in SER measurement. Then, the factors affecting the SER measurement were optimized. By the determination of SER kinetics, cyclic terpenes (1,8-cineole, terpinen-4-ol, menthol and α-terpineol) were demonstrated to possess higher enhancement ratio (ER) values compared with linear terpenes (linalool, geraniol and citral). For the first time, the linear correlation was found between ER of terpenes and the interaction energy of terpene⁻ceramide complexes revealed by molecular simulation. The attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis revealed that the effect of cyclic terpenes on SC lipid arrangement was obviously stronger than that of linear terpenes. In addition, by evaluating HaCaT skin cell viability, little difference was found between the toxicities of cyclic and linear terpenes. In conclusion, measurement of SER could be a feasible approach for the efficient evaluation of the PEs that mainly act on SC lipids.

Silencing of phospholipase C gamma 2 promotes proliferation of rat hepatocytes in vitro.

The management of hepatic failure is undoubtedly difficult, and poor results have led to the search for novel therapeutic approaches. Nowadays, anti-apoptotic gene therapy is considered as an ideal approach. It has been proved that phospholipase Cγ2 (PLCγ2) is involved in the apoptosis of immune cells and tumor cells; however, whether this gene is related to hepatocyte death is still unclear. This study examined the role of PLCγ2 by inhibiting its expression in rat hepatocytes with siRNA. We also further analyzed the cellular mechanism by which the expression inhibition of PLCγ2 induces cell death. Silencing PLCγ2 gene by adenovirus vector expressing PLCγ2-targeted siRNA caused the great decline in the number of G1- and G2/M phase cells, the significant increase in the number of S phase cells, and the obvious reduction in apoptosis index. In addition, silencing PLCγ2 gene relieved the rat hepatocyte damage, such as the cell shrinkage and chromatin condensation, nuclear fragmentation. Further analysis of Ad-PLCγ2 siRNA-transfected hepatocytes demonstrated that suppression of PLCγ2 gene expression could cause the caspase dependent cell death by inhibiting the signal pathway MEKK1/MKK4/JNK1/2/c-Jun. In conclusion, these findings suggest that interference with PLCγ2 expression could relieve the inhibitory effect of PLCγ2 on hepaocyte apoptosis, thus, promote proliferation through inactivating PKCδ-mediated JNK1/2 signaling pathway.

Modulation of ovine SBD-1 expression by Saccharomyces cerevisiae in ovine ruminal epithelial cells.

BACKGROUND: The ovine rumen is involved in host defense responses and acts as the immune interface with the environment. The ruminal mucosal epithelium plays an important role in innate immunity and secretes antimicrobial innate immune molecules that have bactericidal activity against a variety of pathogens. Defensins are cationic peptides that are produced by the mucosal epithelia and have broad-spectrum antimicrobial activity. Sheep ß-defensin-1 (SBD-1) is one of the most important antibacterial peptides in the rumen. The expression of SBD-1 is regulated by the probiotic, Saccharomyces cerevisiae (S.c); however, the regulatory mechanism has not yet been elucidated. In the current study, the effects of S.c on the expression and secretion of SBD-1 in ovine ruminal epithelial cells were investigated using quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). In addition, specific inhibitors were used to block the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), p38, JNK, and ERK1/2 signalling pathways separately or simultaneously, to determine the regulatory mechanism(s) governing S.c-induced SBD-1 upregulation. RESULTS: Incubation with S.c induced release of SBD-1 by ovine ruminal epithelial cells, with SBD-1 expression peaking after 12 h of incubation. The highest SBD-1 expression levels were achieved after treatment with 5.2 × 107 CFU∙mL- 1 S.c. Treatment with S.c resulted in significantly increased NF-κB, p38, JNK, ERK1/2, TLR2, and MyD88 mRNA expression. Whereas inhibition of mitogen-activated protein kinases (MAPKs) and NF-κB gene expression led to a decrease in SBD-1 expression. CONCLUSIONS: S.c was induced SBD-1 expression and the S.c-induced up-regulation of SBD-1 expression may be related to TLR2 and MyD88 in ovine ruminal epithelial cells. This is likely simultaneously regulated by the MAPKs and NF-κB pathways with the p38 axis of the MAPKs pathway acting as the primary regulator. Thus, the pathways regulating S.c-induced SBD-1 expression may be related to TLR2-MyD88-NF-κB/MAPKs, with the TLR2-MyD88-p38 component of the TLR2-MyD88-MAPKs signalling acting as the main pathway.

Characterization of a liposome-based artificial skin membrane for in vitro permeation studies using Franz diffusion cell device.

A prerequisite for successful transdermal or dermal drug therapy is the drug ability to penetration through the skin, especially stratum corneum (SC). The most acceptable technique for measuring skin permeation in vitro is the application of both the Franz diffusion cell device and the skin model. In the skin model, a liposome-based artificial skin membrane (LASM) consisting of tight layers of liposomes immobilized on a filter was prepared and characterized. Using porcine ear skin, rat skin and Strat-M™ artificial membrane as control, the LASM was then evaluated in permeation studies with five active compounds: ferulic acid, paeoniflorin, albiflorin, tetrahydrocolumbamine, and tetrahydropalmatine. The scanning electron microscope images demonstrated complete filling of the membrane pores with lipids and the formation of a continuous liposomal coating. The contents of egg phosphatidylcholine (EPC) and cholesterol in LASM were measured to be 12.08 ± 0.18 and 4.41 ± 0.04 mg/cm2, respectively. Moreover, revealed by the measurement of electrical resistance, the LASM remains intact for at least 12 h with the incubation of 20% ethanol. The results of permeation studies demonstrated a good correlation (r2 = 0.9743, r = 0.9871) of Papp values between the drugs' permeation through LASM and porcine ear skin. In addition, by ATR-FTIR analysis, a slighter shift of CH2 stretching frequency between LASM and porcine ear skin was observed compared with the shift between Strat-M™ membrane and porcine ear skin. In summary, for the first time, the LASM has been proved to be a valuable alternative to porcine ear skin in permeation studies using Franz diffusion cell device.

Protective effect of selenomethionine on rabbit testicular injury induced by Aflatoxin B1.

The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood-testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.

Brain abscess from oral microbiota approached by metagenomic next-generation sequencing: A case report and review of literature.

BACKGROUND: Brain abscess is a serious and potentially fatal disease caused primarily by microbial infection. Although progress has been made in the diagnosis and treatment of brain abscesses, the diagnostic timeliness of pathogens needs to be improved. CASE SUMMARY: We report the case of a 54-year-old male with a brain abscess caused by oral bacteria. The patient recovered well after receiving a combination of metagenomic next-generation sequencing (mNGS)-assisted guided medication and surgery. CONCLUSION: Therefore, mNGS may be widely applied to identify the pathogenic microorganisms of brain abscesses and guide precision medicine.

GRK2 inhibits Flt-1+ macrophage infiltration and its proangiogenic properties in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2f/fLyz2-Cre+/- mice. Synovial inflammation and M1 polarization were improved in GRK2f/fLyz2-Cre+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1+ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

The stability of physicians' risk attitudes across time and domains.

Risk attitude is known to influence physicians' decision-making under uncertainty. Research on the risk attitudes of physicians is therefore important in facilitating a better understanding of physicians' decisions. However, little is known about the stability of physicians' risk attitudes across domains. Using five waves of data from a prospective panel study of Australian physicians from 2013 to 2017, we explored the stability of risk attitudes over a four-year period and examined the association between negative life events and risk attitudes among 4417 physicians. Further, we tested the stability of risk attitude across three domains most relevant to a physician's career and clinical decision-making (financial, career and clinical). The results showed that risk attitude was stable over time at both the mean and individual levels but the correlation between domains was modest. There were no significant associations between negative life events and risk attitude changes in all three domains. These findings suggest that risk attitude can be assumed to be constant but domain-specificity needs to be considered in analyses of physician decision-making.

Extracellular matrix in synovium development, homeostasis and arthritis disease.

Extracellular matrix (ECM) is a three-dimensional network entity composed of extracellular macromolecules. ECM in synovium not only supports the structural integrity of synovium, but also plays a crucial role in regulating homeostasis and damage repair response in synovium. Obvious disorders in the composition, behavior and function of synovial ECM will lead to the occurrence and development of arthritis diseases such as rheumatoid arthritis (RA), osteoarthritis (OA) and psoriatic arthritis (PsA). Based on the importance of synovial ECM, targeted regulation of the composition and structure of ECM is considered to be an effective measure for the treatment of arthritis disease. This paper reviews the current research status of synovial ECM biology, discusses the role and mechanism of synovial ECM in physiological status and arthritis disease, and summarizes the current strategies for targeting synovial ECM to provide information for the pathogenesis, diagnosis and treatment of arthritis disease.

Immune-mediated necrotizing myopathy: Report of two cases.

BACKGROUND: Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase, with unique skeletal muscle pathology and magnetic resonance imaging features. CASE SUMMARY: In this paper, two patients are reported: One was positive for anti-signal recognition particle antibody, and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody. CONCLUSION: The clinical characteristics and treatment of the two patients were analysed, and the literature was reviewed to improve the recognition, diagnosis, and treatment of this disease.

Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats.

Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of transplanted stem cells, which weakens the therapeutic efficacy of ADSCs. Resveratrol (Res) is a type of natural polyphenol compound that regulates the proliferation, senescence and differentiation of stem cells. Therefore, we investigated whether incubation of ADSCs with Res improves their to promote peripheral nerve regeneration. ADSCs were cultured in vitro and treated with H2O2 to establish an apoptosis model. The control, H2O2 and Res groups were set up. The cell survival rate was detected by the CCK-8 method. The TUNEL assay was used to detect the apoptosis of the cells. qRT‒PCR was used to analyze the expression of apoptosis-related mRNA, and the effect of Res on the proliferation of ADSCs was investigated. In vivo, 40 SD rats were randomly divided into the control, model, ADSCs and ADSC + Res groups, with 13 rats in each group. The sciatic nerve injury rat model was established by the clamp method. Gait was observed on Days 7, 14, 21, and 28. Sciatic nerve regeneration was detected on Day 28. Res had no effect on the proliferation of ADSCs, and the TUNEL assay confirmed that Res pretreatment could significantly improve H2O2-induced apoptosis in ADSCs. Compared with the control group, caspase-3, Bax and Bcl-2 expression levels were significantly increased in the H2O2 group. Compared with the H2O2 group caspase-3 and Bax expression levels were significantly decreased, and Bcl-2 expression levels were significantly increased in ADSCs + Res group. At 4 weeks after surgery, the functional index of the sciatic nerve in the ADSCs + Res group was significantly higher than that in the model group. On Day 28, the average density of the sciatic nerve myelin sheath in the ADSCs + Res group was significantly increased compared with that in the model group, and Nissl staining showed that the number of motor neurons in the spinal cord was significant compared with that in the model group. Compared with the control group, the wet weight ratio of gastrocnemius muscle and muscle fiber area in ADSCs + Res group were significantly increased. Res enhanced the ability of ADSCs to promote sciatic nerve regeneration in rats.