Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings / Aplicação exógena de ácido salicílico induz tolerância à salinidade em mudas de berinjela

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

A molecular approach to triple-negative breast cancer: targeting the Notch signaling pathway

ABSTRACT Introduction Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This phenotype renders triple-negative breast cancer cells refractory to conventional therapies, resulting in poor clinical outcomes and an urgent need for novel therapeutic approaches. Recent studies have implicated dysregulation of the Notch receptor signaling pathway in the development and progression of triple-negative breast cancer. Objective This study aimed to conduct a comprehensive literature review to identify potential therapeutic targets of the Notch pathway. Our analysis focused on the upstream and downstream components of this pathway to identify potential therapeutic targets. Results Modulating the Notch signaling pathway may represent a promising therapeutic strategy to treat triple-negative breast cancer. Several potential therapeutic targets within this pathway are in the early stages of development, including upstream (such as Notch ligands) and downstream (including specific molecules involved in triple-negative breast cancer growth). These targets represent potential avenues for therapeutic intervention in triple-negative breast cancer. Comments Additional research specifically addressing issues related to toxicity and improving drug delivery methods is critical for the successful translation of these potential therapeutic targets into effective treatments for patients with triple-negative breast cancer.

Signal mining and analysis of selinexor adverse events / 中国药房

OBJECTIVE To mine the adverse drug event （ADE） signals of selinexor， and to provide reference for its clinical safety medication. METHODS ADE data for selinexor reported from July 3rd， 2019 to March 31st， 2023 were collected from the FDA adverse event reporting system （FAERS）. Data mining was performed by using the reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods， and categorization statistics were performed by using the system organ class （SOC） and preferred term （PT） from drug ADE terminology set in the MedDRA （version 26.0）. RESULTS A total of 3 084 ADE reports were obtained for selinexor， with a total of 134 ADE-positive signals. Among the reported genders， there were 127 males and 124 females， with a predominant age of ≥65 years old （4.12%）； the United States had the highest number of reports （96.53%）， with consumers being the main reporters （77.27%）； severe ADR was mainly characterized by hospitalization/prolonged hospitalization （26.26%）， followed by death （17.15%）. The top 3 ADE in the list of frequency were nausea （1 162 times）， fatigue （790 times） and anorexia （610 times）， all of which were mentioned in the selinexor’s instructions. The top 3 signals in the list of strength were device-associated bacteremia （ROR＝115.07， PRR＝114.94）， blepharospasm dysfunction （ROR＝106.70， PRR＝106.54）， and salmonella sepsis （ROR＝99.90， PRR＝99.81）， all of which were not mentioned in the selinexor’s instructions. CONCLUSIONS In addition to the ADE of nausea mentioned in the instruction manual， attention should also paid to device-associated bacteremia， blepharospasm dysfunction， salmonella sepsis， and other ADE not mentioned in the instruction manual when using selinexor in clinical practice； weekly rechecking of the patient’s blood routine should be done to monitor the patient’s blood indexes， symptoms of infection， and so on， to ensure that the safety of 1661962346@qq.com drug use.

Construction of competitive endogenous RNA network mediated by lung ischemia-reperfusion core genes / 器官移植

Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.

Bluetooth Coupling in Hearing Aids: Effect on Audiovisual Speech Recognition and Quality Rating of Compressed Speech in Older Individuals with Sloping Hearing Loss

Abstract Introduction Older individuals often report that they find it difficulty in enjoying watching television since they find it hard to follow the rapid intensity variations, and voice changes from scene to scene. Objective The present study investigated the effect of coupling the hearing aid with the television via Bluetooth on audiovisual speech recognition and quality rating of compressed speech in older individuals with hearing loss. Method Twenty participants in the age range of 60 to 75 years who had moderate to moderately severe sloping sensorineural hearing loss were bilaterally fitted with digital receiver in the canal hearing aids. The hearing aid was coupled with a television via Bluetooth using a streamer. The video recorded stimuli were presented at 65 dB SPL at normal rate, 35% compression and 45% compression conditions. Speech recognition scores and quality ratings were obtained for each condition with and without the Bluetooth streamer connected to the hearing aids. Results Speech recognition scores were significantly better with Bluetooth coupling compared with conventional hearing aid use at 40% compressed speech rate. The quality was also rated higher in almost all parameters across speech rates when Bluetooth was used. Conclusions The improved clarity and nullification of room reverberation offered by Bluetooth coupling can potentially compensate for the age-related temporal processing deficit contributing to ease of listening.

Elastic Recoil Signal on Tissue Doppler Imaging of Mitral Annulus as a Qualitative Test to Identify Left Ventricular Diastolic Function

Introduction: Left ventricular (LV) diastolic dysfunction is common on preoperative screening among patients undergoing surgery. There is no simple screening test at present to suspect LV diastolic dysfunction. This study was aimed to test the hypothesis, whether elastic recoil signal (ERS) on tissue Doppler imaging of mitral annulus (MA TDI) can be used as a qualitative test to differentiate patients from normal LV diastolic function versus patients with LV diastolic dysfunction. Methods: This was a prospective cross-sectional observational study of patients admitted for elective surgeries. Normal diastolic function and categorization of LV diastolic dysfunction into severity grades I, II, or III were performed as per the American Society of Echocardiography/ European Associationof Cardio Vascular Imaging (ASE/EACVI) recommendations for LV diastolic dysfunction. Results: There were 41 (61%) patients with normal LV diastolic function and 26 (39%) patients with various grades of LV diastolic dysfunction. In 38 out of 41 patients with normal LV diastolic function, the characteristic ERS was identified. The ERS was absent in all the patients with any grade of LV diastolic dysfunction. Consistency of identification of ERS on echocardiography was tested with a good interobserver variability coefficient of 0.94 (P-value <0.001). The presence of ERS demonstrated an excellent differentiation to rule out any LV diastolic dysfunction with an area under the receiver operating characteristics curve (AUROC) of 0.96 (CI 0.88�99; P value <0.001). Conclusions: To conclude, in a mixed surgical population, the anesthetist could successfully assess LV diastolic dysfunction in the preoperative period and the characteristic ERS on MA TDI signal can be used as a qualitative test to differentiate patients from normal LV diastolic function versus patients with LV diastolic dysfunction using the transthoracic echocardiography (TTE).

Lenvatinib down-regulates IGF1R/Mek/Erk signaling pathway in the treatment of regorafenib-resistant hepatocellular carcinoma / 中华肿瘤杂志

Objective: To investigate the therapeutic effect and mechanism of lenvatinib on regorafenib-resistant hepatocellular carcinoma cells. Methods: CCK-8 and clone formation assay were used to observe the inhibitory effect of lenvatinib on the growth of hepatocellular carcinoma cells. Flow cytometry was used to detect the apoptosis of regorafenib-resistant hepatocellular carcinoma cells treated with lenvatinib. The expression levels of related proteins were detected by western blot and immunohistochemical staining. The inhibitory effect of lenvatinib on the tumor formation ability of regorafenib-resistant hepatocellular carcinoma cells in vivo was observed by subcutaneous tumor formation experiment in mice. Results: CCK-8 and clone formation assay showed that lenvatinib could inhibit the proliferation of regorafenib-resistant hepatocellular carcinoma cells. The number of clones of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group (120.67±11.06, 53.00±11.14, 55.00±9.54, 78.67±14.64) were all lower than those in control group (478.00±24.52, 566.00±27.87, 333.67±7.02, 210.00±12.77, all P<0.05). Flow cytometry showed that lenvatinib could promote apoptosis of regorafenib-resistant hepatocellular carcinoma cells, the apoptosis rates of HepG2, SMMC7721 and regorafenib-resistant HepG2, SMMC7721 cells in lenvatinib group [(12.30±0.70)%, (9.83±0.38)%, (15.90±1.32)%, (10.60±0.00)%] were all higher than those in control group [(7.50±0.87)%, (5.00±1.21)%, (8.10±1.61)%, (7.05±0.78)%, all P<0.05]. The apoptosis-related protein levels suggested that apoptosis was increased in the treatment of lenvatinib. The animal study showed that lenvatinib can inhibit the growth of regorafenib-resistant cells in vivo. Immunohistochemistry and western blot results showed that lenvatinib could down-regulate the abnormally activated IGF1R/Mek/Erk signaling pathway in regorafenib-resistant cells. Conclusion: Lenvatinib can reverse regorafenib resistance in hepatocellular carcinoma, possibly by down-regulating IGF1R/Mek/Erk signaling pathway.

Protective role of vasonatrin peptide in hepatic ischemia-reperfusion injury in rats through activation of extracellular signal-regulated kinase signaling pathway / 中华肝胆外科杂志

Objective:To investigate the protective role of extracellular signal-regulated kinase (ERK) signaling pathway in the process that vasonatrin peptide (VNP) reduces hepatic ischemia-reperfusion injury in rats.Methods:Twenty SD rats, weighting 200-250 g, were randomly divided into four groups and each group has five rats. The four groups were sham operation group (S group), ischemia-reperfusion group (I/R group), VNP group (V group) and PD98059+ VNP group (P+ V group). In the rat model of hepatic warm ischemia and reperfusion, the hepatic artery and portal vein of the left lobe and middle lobe of the liver were clamped with arterial clamp for 45 min followed by reperfusion for 120 min. In the V group, VNP (50 μg/kg) was injected 10 minutes before ischemia. In the P+ V group, PD98059 (2 mg/kg) was injected 20 min before VNP injection followed by VNP administration and I/R treatment. The serum levels of alanine amino transaminase (ALT), aspartate amino transferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and the superoxide dismutase (SOD) in liver tissue homogenate and malondialdehyde (MDA) were measured. The histopathology of liver tissue was observed. The contents of p-ERK1/2 were detected by Western blot.Results:Compared with S group, in I/R group and P+ V group the serum levels of ALT [(489.65±11.22), (333.05±24.77) vs. (33.78±4.88) U/L], AST [(651.43±14.99), (503.18±21.48) vs. (154.84±12.32) U/L], TNF-α [(12.83±1.09), (9.64±0.57) vs. (2.11±0.11) ng/L], IL-1β [(7.19±0.62), (5.12±0.22) vs. (1.10±0.49) ng/L], MDA [(8.00±0.88), (5.60±1.01) vs. (2.76±1.29) μmol/mg] increased, while SOD [(54.89±10.60), (68.85±8.33) vs. (126.10±15.63) nmol/mg]decreased (all P<0.05). The histopathology of liver tissue revealed that liver structure damaged more seriously in I/R group and P+ V group. Western blot analysis showed that p-ERK1/2 decreased significantly in I/R group and P+ V group. Compared with I/R group, ALT, AST, MDA, TNF-α and IL-1β decreased significantly and SOD increased significantly in V group (all P<0.05). The histopathology of liver tissue revealed that liver structure was damaged slightly, and p-ERK1/2 increased significantly in V group compared with I/R group ( P<0.05). Conclusion:VNP can significantly reduce hepatic ischemia-reperfusion injury through activation of p-ERK1/2 signaling pathway and inhibition of hepatocyte inflammatory response.

The role and treatment strategy of epithelial-mesenchymal transition in radiation-induced pulmonary fibrosis / 中华放射医学与防护杂志

Radiation-induced pulmonary fibrosis (RIPF) is one of the most serious late complications after nuclear radiation accident, bone marrow transplantation pretreatment and thoracic tumor radiotherapy. The formation process of RIPF is complicated and the pathogenesis has not been fully elucidated. Recent studies have shown that radiation-induced epithelial-mesenchymal transition (EMT) of lung epithelial cells is an indispensable segment of RIPF. This article reviews the role of radiation-induced lung EMT in the occurrence and development of RIPF and related drugs with EMT as a potential therapeutic target, providing ideas for the development of therapeutic drugs for RIPF in the future.

Expression of decoy receptor 3 and its signaling pathway in ankylosing spondylitis and its clinical significance / 中华风湿病学杂志

Objective:To investigate the expression and clinical significance of decoy receptor 3 (DcR3) and its signal pathway-related molecules in PBMCs of patients with ankylosing spondylitis (AS).Methods:Peripheral blood samples, clinical data and laboratory test results were collected from 100 patients with ankylosing spondylitis [50 patients with AS activity (ASA), 50 patients with AS stability (ASS)], 30 patients with osteoarthritis and 30 patients with gouty arthritis (as disease control group), and 60 healthy controls (HC). The mRNA expression levels of DcR3 and its signal pathway related genes (DR3, TL1A, Fas, FasL, LIGHT, LIGHTR, LTβR) were measured by real-time fluorescence quantitative polymerase chain reaction. Measurement data among the three groups in normal distribution were analyzed by t test or one-way analysis of variance, pairwise comparisons using LSD- t test, non-normal distribution data were analyzed by Mann-Whitney test or Kruskal-Wallis H test, χ2 test was used for correlation analysis of categorical variables. Correlation analysis between variables were analyzed using Spearman correlation analysis. Results:① By comparing the AS group, disease control group and HC group, the expression levels of DcR3 mRNA and DR3 mRNA in the AS group were lower than those in disease control group and HC group, and DcR3 mRNA and DR3 mRNA in disease control group were lower than those in the HC group {DcR3mRNA: [6.21 (3.89, 10.70)]×10 -4vs [9.51 (5.89, 16.65)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=55.28, P<0.001; DR3 mRNA: [41.05 (24.09, 66.95)]×10 -4vs [58.28 (28.41, 94.38)]×10 -4vs [94.79 (54.07, 144.51)]×10 -4, H=37.10, P<0.001}. The expression level of TL1A mRNA in the AS group was higher than that in disease control group {[14.71(4.91, 42.22)]×10 -4vs [4.00(1.07, 16.60)]×10 -4vs [7.70 (3.52, 27.83)]×10 -4, H=17.71, P<0.001}; The expression level of Fas mRNA in AS group and disease control group was lower than that in HC group {[20.99(4.63, 62.89)]×10 -4vs [23.97(15.82, 38.99)]×10 -4vs [78.45 (27.32, 146.46)]×10 -4, H=31.17, P<0.001}. The expression level of FasL mRNA in AS group was higher than that in disease control group and HC group {[42.87(6.57, 91.21)]×10 -4vs [5.45(2.83, 10.32)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=46.42, P<0.001}. The expression level of LIGHTR mRNA in AS group was lower than that in disease control group {[52.66 (7.20, 143.21)]×10 -4vs [98.80 (53.11, 166.24)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.96, P<0.001}. There were no significant differences in LIGHT mRNA and LTβR mRNA among all groups ( H=0.86, P>0.05; H=3.18, P>0.05). ②The expression levels of DcR3 mRNA, DR3 mRNA and Fas mRNA in ASA group and ASS group were lower than those in HC group. DcR3 mRNA in ASA group was higher than that in ASS group, and DR3 mRNA in ASA group was lower than that in ASS group {DcR3 mRNA: [7.28 (4.92, 16.56)]×10 -4vs [4.59 (2.49, 7.03)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=62.63, P<0.001; DR3 mRNA: [30.93(16.18, 66.66)]×10 -4vs [47.17(29.91, 67.40)]×10 -4vs [94.79(54.07, 144.51)]×10 -4, H=41.48, P<0.001; Fas mRNA: [20.04(3.29, 62.30)]×10 -4vs [22.49(5.63, 64.79)]×10 -4vs [78.45(27.32, 146.46)]×10 -4, H=23.54, P<0.001}. The expression levels of TL1A mRNA and LTβR mRNA in the ASA group were higher than those in the ASS group and the HC group {TL1A mRNA: [32.36(10.09, 97.84)]×10 -4vs [9.98(1.29, 21.63)]×10 -4vs [7.70(3.52,27.83)]×10 -4, H=21.14, P<0.001; LTβR mRNA: [6.13(2.16,20.06)×10 -4vs [2.13(0.53,8.04)]×10 -4vs [2.72 (1.24,5.73)]×10 -4, H=12.86, P<0.001}. The expression level of FasL mRNA in the ASA group and the ASS group was higher than that in the HC group {[60.70 (8.16, 106.16)]×10 -4vs [30.14 (5.37, 78.40)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=18.99, P<0.001}. The expression level of LIGHTR mRNA in ASS group was lower than that in HC group {[49.79(10.75, 168.48)]×10 -4vs [15.92(3.27, 105.91)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.80, P<0.001]. There was no significant difference in LIGHT mRNA among all groups ( H=4.15, P>0.05). ③Spearman correlation analysis showed that DcR3 level was positively correlated with BASDAI score and hsCRP in AS patients ( r=0.52, P<0.001; r=0.35, P<0.01), and DR3 level was negatively correlated with BASDAI score, ESR and hsCRP level ( r=-0.28, P<0.001; r=-0.25, P<0.001; r=-0.31, P<0.001). TL1A was positively correlated with BASDAI score, ESR and hsCRP level ( r=0.23, P=0.046; r=0.26, P=0.015; r=0.25, P=0.017). Conclusion:DcR3 and its signal pathway-related molecules are differentially expressed in PBMCs of patients with AS, suggesting that they may participate in the occurrence and development of AS.

The evaluation value of MRI dynamic enhancement TIC combined with DWI in benign and malignant breast lesions / 中国医师杂志

Objective:To explore the clinical application value of dynamic contrast-enhanced MRI (DCE) time-signal intensity curve (TIC) combined with diffusion weighted imaging (DWI) in the diagnosis of benign and malignant breast lesions.Methods:This study was a retrospective study. 95 patients with suspected breast cancer who were diagnosed and treated in the Beijing Huairou Hospital from October 2018 to October 2021 were taken as the study subjects. All patients received DCE-TIC and DCE-DWI examinations, and then underwent needle biopsy after imaging examination. We evaluated the diagnostic efficacy of DCE-TIC and DCE-DWI alone and in combination in benign and malignant breast lesions by collecting general clinical data and apparent diffusion coefficient (ADC) values of patients, using pathological examination results as the " gold standard" .Results:A total of 95 patients with suspected breast cancer were diagnosed as benign lesions in 25 cases and malignant lesions in 70 cases after biopsy. Compared with benign lesions, the tumor diameter and ADC value of malignant lesions were significantly different (all P<0.05). The eceiver operating characteristic (ROC) curve of subjects was drawn, and the area under the curve (AUC) of DCE-DWI diagnosis of breast cancer was 0.826. 95 suspected breast cancer patients were diagnosed by DCE-TIC in 28 cases of type Ⅰ, 27 cases of type Ⅱ, and 40 cases of type Ⅲ. With the pathological diagnosis results as the " gold standard", the accuracy, sensitivity, and negative predictive value of DCE-TIC combined with DCE-DWI in the diagnosis of breast cancer were higher than those of a single diagnosis, with a statistically significant difference (all P<0.05); The specificity and positive predictive value of combined diagnosis were not statistically significant compared to single diagnosis (all P>0.05). Conclusions:Both DCE-TIC and DCE-DWI can differentiate benign and malignant breast lesions, and the accuracy, sensitivity, and positive predictive value of combined diagnosis are higher than those of single diagnosis. The combination of DCE-TIC and DCE-DWI can help improve the differential efficiency of breast lesion properties.

Signal transducer and activator of transcription 6 mediates skeletal muscle cell injury in septic mice by regulating ferroptosis / 中华危重病急救医学

Objective:To explore the effect of signal transducer and activator of transcription 6 (STAT6) on ferroptosis in skeletal muscle cells in sepsis model and its potential mechanism.Methods:Twenty-four 8-week-old male specific pathogen free Kunming mice were divided into normal control group, sham group, sepsis model group and STAT6 inhibitor pretreatment group according to random number table method with 6 mice in each group. A mouse sepsis model was reproduced by cecal ligation and perforation (CLP). In the sham group, the skin of mice was sutured after exposing the cecum tissue. In the STAT6 inhibitor pretreatment group, 10 mg/kg AS1517499 was injected intraperitoneally 1 hour before model reproduction. The sham group and the model group were intraperitoneally injected with the same volume of normal saline. Mice in the normal control group did not receive any operation or drug intervention. The mice were sacrificed 24 hours after model reproduction, and the muscle tissue of hind limb was obtained under sterile condition. Hematoxylin-eosin (HE) staining was used to observe the histopathology with optical microscope, and mitochondrial morphological changes were observed by transmission electron microscopy after double staining with uranium acetate lead citrate. The ferroptosis marker proteins expressions of chitinase-3-like protein 1 (CHI3L1), cyclooxygenase-2 (COX-2), acyl-CoA synthetase long-chain family member 4 (ACSL4), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPx4) were detected by Western blotting.Results:Under the optical microscope, the morphology and structure of skeletal muscle tissues in the normal control and sham groups were normal. In the model group, the structure of skeletal muscle tissues was loose, the muscle fiber became smaller and atrophic, inflammatory cell infiltration and even muscle fiber loss were found. Compared with the model group, the structure of skeletal muscle tissues was tight and skeletal muscle atrophy was improved in the STAT6 inhibitor pretreatment group. The ultrastructure of skeletal muscle cell in the normal control and sham groups was normal under transmission electron microscope. The ultrastructure characteristics of skeletal muscle in the model group showed that cell membrane was broken and blister, mitochondria became smaller and membrane density increased, the mitochondrial crista decreased or disappeared, the mitochondrial outer membrane was broken, and the nucleus was normal in size but lacked chromatin condensation. Compared with the model group, the STAT6 inhibitor pretreatment group had a significant improvement in the ultrastructure of muscle cells. Compared with the normal control and sham groups, the protein expressions of CHI3L1, COX-2, ACSL4 and FTH1 in the muscle of the model group were significantly increased, while the protein expression of GPx4 was decreased significantly, indicating that the skeletal muscle cells in the mouse sepsis model showed characteristic mitochondrial injury and abnormal expression of ferroptosis markers. Compared with the model group, the protein expressions of CHI3LI, COX-2, ACSL4 and FTH1 in the STAT6 inhibitor pretreatment group were significantly decreased [CHI3L1 protein (CHI3L1/GAPDH): 0.70±0.08 vs. 0.97±0.09, COX-2 protein (COX-2/GAPDH): 0.61±0.03 vs. 0.83±0.03, ACSL4 protein (ACSL4/GAPDH): 0.75±0.04 vs. 1.02±0.16, FTH1 protein (FTH1/GAPDH): 0.49±0.06 vs. 0.76±0.13, all P < 0.05], while the protein expression of GPx4 was significantly increased (GPx4/GAPDH: 1.14±0.29 vs. 0.53±0.03, P < 0.05). Conclusions:Sepsis can induce ferroptosis in skeletal muscle cells of mice. STAT6 may mediate ferroptosis in mouse skeletal muscle cells by regulating the expressions of COX-2, ACSL4, FTH1 and GPx4, thereby inducing skeletal muscle cell injury in sepsis.

Progress in the effect of fluorosis on skeletal muscle and its related molecular mechanisms / 中华地方病学杂志

Fluoride has dual health effects. Proper amount of fluoride plays an important role in bone development, prevention of dental caries and nervous system activity. Excessive fluoride causes chronic systemic diseases with dental fluorosis and skeletal fluorosis as the main symptoms. Fluorosis causes morphological and structural changes and function damage in skeletal muscle. Low concentration of fluoride induces muscle canal hypertrophy in skeletal muscle, while high concentration of fluoride leads to skeletal muscle atrophy by causing a series of signal pathway abnormalities. Abnormal changes in phosphatidylinositol-3-hydroxykinase/protein kinase B (PI3K/Akt) signal pathway, oxidative stress, and ubiquitin-proteasome pathway all play important roles in skeletal muscle injury caused by fluorosis. In this paper, the effect of fluoride on skeletal muscle and its related molecular mechanisms are reviewed.

Progress in molecular signal pathway of dental fluorosis / 中华地方病学杂志

Dental fluorosis is a manifestation of chronic oral fluorosis caused by excessive fluoride intake in childhood. At present, the molecular mechanism of dental fluorosis is still unclear. Ameloblasts are the most sensitive cells to fluoride in tooth tissue. Fluoride affects the proliferation and secretion of ameloblasts through the role of key molecules in the molecular signal pathways, leading to the formation of dental fluorosis. This paper reviews the relationship between the molecular signal pathways [mitogen-activated protein kinase (MAPK), transforming growth factor-β (TGF-β)/Smad, Wnt, Foxo1/Runx2], stress pathways (endoplasmic reticulum stress and oxidative stress) and the occurrence of dental fluorosis in recent years, in order to deeply understand the pathogenesis of dental fluorosis at the molecular level, and provide new ideas for the prevention and treatment of dental fluorosis.

Application of "Flipped Classroom" in comprehensive experiment teaching of Digital Signal Processing for biomedical engineering specialty / 中华医学教育探索杂志

"Flipped Classroom" is a new kind of "student-centered" teaching model, which can give full play to the advantages of both sides of teaching and learning. According to this teaching model, we redesigned the teaching process, in which the students studied by themselves and built their own knowledge system. Moreover, each of them took part in three stages of experimental design including digital signal collection, analysis and processing in groups. Results have shown that this model can fully stimulate students' learning interest, not only helps students to deepen understanding of digital signal processing theory knowledge, but also strengthen the ability of autonomous learning and team collaboration. The teaching model maybe have certain reference function in comprehensive experiment teaching of Digital Signal Processing course for biomedical engineering specialty.

Personal glucose meters coupled with signal amplification technologies for quantitative detection of non-glucose targets:Recent progress and challenges in food safety hazards analysis / 药物分析学报

Ensuring food safety is paramount worldwide.Developing effective detection methods to ensure food safety can be challenging owing to trace hazards,long detection time,and resource-poor sites,in addition to the matrix effects of food.Personal glucose meter(PGM),a classic point-of-care testing device,possesses unique application advantages,demonstrating promise in food safety.Currently,many studies have used PGM-based biosensors and signal amplification technologies to achieve sensitive and specific detection of food hazards.Signal amplification technologies have the potential to greatly improve the analytical performance and integration of PGMs with biosensors,which is crucial for solving the challenges associated with the use of PGMs for food safety analysis.This review introduces the basic detection principle of a PGM-based sensing strategy,which consists of three key factors:target recog-nition,signal transduction,and signal output.Representative studies of existing PGM-based sensing strategies combined with various signal amplification technologies(nanomaterial-loaded multienzyme labeling,nucleic acid reaction,DNAzyme catalysis,responsive nanomaterial encapsulation,and others)in the field of food safety detection are reviewed.Future perspectives and potential opportunities and challenges associated with PGMs in the field of food safety are discussed.Despite the need for complex sample preparation and the lack of standardization in the field,using PGMs in combination with signal amplification technology shows promise as a rapid and cost-effective method for food safety hazard analysis.

LED red light up-regulates MAPK signal to promote osteogenic/odontogenic differentiation of human dental pulp stem cells in an inflammatory environment / 口腔疾病防治

Objective @#To study the effect of light-emitting diode (LED) red light on the osteogenic/odontogenic differentiation of human dental pulp stem cells (hDPSCs) and its mechanism were discussed. @*Methods@#This study has been reviewed and approved by the Ethics Committee. hDPSCs were cultured by tissue block enzyme digestion. The proliferative capacity of hDPSCs was detected by the CCK-8 at days 1, 3, 5 and 7 under stimulation with 0, 1, 5 and 10 μg/mL lipopolysaccharide (LPS), and the LPS stimulatory concentration was screened. The CG group (mineralization induction), LPS+CG group, and LPS+CG+ (2, 4, 6, 8, and 10 J/cm2) LED red light groups were set. On day 7, alkaline phosphatase (ALP) staining and ALP activity were determined. Relative expression levels of the ALP, osterix (OSX), dentin matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) genes were measured by qRT-PCR. On day 21, alizarin red staining and calcium nodule quantitative determination were performed to screen the best light energy. The LPS+CG group and LPS+CG+LED group (optimal energy) were set up, and the secretion and expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by ELISAs on days 1, 3, 5 and 7. The relative expression levels of the extracellular regulated protein kinases 1/2 (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and extracellular regulated protein kinases 5 (ERK5) proteins and their phosphorylated proteins in the MAPK signaling pathway were detected by Western blots. After the pathway was blocked, the relative expression levels of the ALP, OSX, DMP-1, and DSPP proteins after LED red light irradiation on day 7 were detected by Western blots.@*Results@# CCK-8 assays showed that the proliferation of hDPSCs induced by 10 μg/mL LPS was lower than that of the 0, 1, and 5 μg/mL groups on the 5th and 7th days (P<0.05), and 10 μg/mL was selected as the LPS stimulatory concentration in the follow-up experiment. ALP staining, ALP activity, gene expression levels of ALP, OSX, DMP-1 and DSPP and calcium nodule quantification in the LPS+CG+4 J/cm2 group were higher than those in the other treatment groups (P<0.05). 4 J/cm2 LED red light had the strongest ability to promote osteogenic/odontogenic differentiation and was used as the LED light energy density in subsequent experiments. ELISA showed that the secretion and expression levels of TNF-α and IL-1β in the LPS+CG+LED group were lower than those in the LPS+CG group on the 5th and 7th days (P<0.05). Western blot analysis showed that 4 J/cm2 LED red light promoted the expression levels of the p-ERK1/2, p-p38, p-JNK and p-ERK5 proteins. After the MAPK pathway was blocked, the expression levels of the ALP, OSX, DMP-1, and DSPP proteins in the LPS+CG+LED+U0126 (ERK1/2 inhibitor), SP600125 (JNK inhibitor), and BIX02189 (ERK5 inhibitor) groups were lower than those in the LPS+CG+LED group (P<0.001). The protein expression levels of ALP, OSX and DMP-1 in the LPS+CG+LED+SB203580 (p38 inhibitor) group were not significantly different from those in the LPS+CG+LED group (P>0.05).@*Conclusion@#In inflammatory conditions, LED red light promotes osteogenic/odontogenic differentiation of hDPSCs. This effect may be attributed to enhancement of the ERK1/2, JNK, and ERK5 signaling pathways, which reduces the production of the inflammatory cytokines TNF-α and IL-1β.

Signals mining and analysis of adverse drug events of pazopanib based on FAERS database / 中国药房

OBJECTIVE To mine and analyze adverse drug event （ADE） signals after the marketing of pazopanib and provide references for clinically safe medication. METHODS OpenVigil 2.1 data platform was used to mine ADE signals from the US FDA adverse event reporting system （FAERS） database. ADE reports of pazopanib from October 2009 to June 2022 were collected， and ADE signals were analyzed using proportional reporting ratio （PRR） method and reporting odds ratio （ROR） method in the proportional imbalance method. RESULTS A total of 16 655 ADE reports were identified with pazopanib as the primary suspect drug. Through ROR and PRR analysis， 220 ADE signals involving 19 system organ classes were identified. The top 10 ADE signals by frequency were recorded in the drug instruction. Additionally， 88 new ADE signals were discovered， mainly related to the gastrointestinal system， various investigations， and the renal and urinary system. Decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula were both new ADE signals and the top 10 ADE signals by strength. CONCLUSIONS The occurrence of common ADEs （diarrhea， hair color changes， hypertension， etc.） during the use of pazopanib after marketing is generally consistent with its drug instruction； the number of reported cases for new suspected risk signals （decreased basophil count， nail bed hemorrhage， tumor rupture， and vaginal fistula， etc.） is limited， and continuous monitoring is required.

Influences of notoginsenoside R1 on the injury of alveolar epithelial cells infected by Klebsiella pneumoniae by regulating JAK2STAT3 signaling pathway / 中国热带医学

@#Abstract: Objective　To investigate the influences of notoginsenoside R1 (NGR1) on cell injury and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway of alveolar epithelial cells infected by Klebsiella pneumoniae (Kp). Methods　A549 cells were grouped into five groups: control group (C group), infection group (Infect group), infection + low NGR1 group (Infect + L-NGR1 group), infection + high NGR1 group (Infect + H-NGR1 group), and infection+high NGR1+JAK2/STAT3 pathway inhibitor group (Infect+H-NGR1+SD-1029 group). Cell proliferation was measured using CCK8; ELISA kits were applied to detect the contents of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in the culture medium; flow cytometry was applied to detect apoptosis; RT-qPCR was applied to detect the expressions of JAK2/STAT3; Western blot was applied to detect JAK2/STAT3 pathway, autophagy protein microtubule-associated protein 1 light chain 3 (LC3), autophagy-relatedgene5 (Atg5), autophagy-related gene (Atg) 6 (Beclin-1), apoptosis protein B-cell lymphoma 2 (Bcl-2), Bcl-2-accociated protein (Bax), cysteinyl aspartate specific proteinase (cleaved-caspase-3) proteins expression. Results　Compared with the C group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect group were obviously decreased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Compared with Infect group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect+L-NGR1 group and Infect+H-NGR1 group were obviously increased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-Caspase-3 were obviously decreased (P<0.05). Compared with Infect+H-NGR1 group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the protein phosphorylation levels of JAK2, STAT3 in the Infect+H-NGR1+SD-1029 group were obviously decreased (P<0.05), and the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Conclusions NGR1 can activate the JAK2/STAT3 signaling pathway, promote autophagy of alveolar epithelial cells, and inhibit Kp-induced inflammatory injury and apoptosis of alveolar epithelial cells.