Mechanism of action of formononetin in alleviating allergic asthma through DRP1-NLRP3 signaling pathway / 中国药理学通报

Aim To investigate the mechanism by which formononetin (FN) inhibits mitochondrial dynamic-related protein 1 (DRP1) -NLRP3 axis via intervening the generation of ROS to reduce allergic airway inflammation. Methods In order to establish allergic asthma mouse model, 50 BALB/c mice aged 8 weeks were divided into the control group, model group, FN treatment group and dexamethasone group after ovalbumin (OVA) induction. Airway inflammation and collagen deposition were detected by HampE and Masson staining. Th2 cytokines and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, ROS in BEAS-2B cells was assessed by DCFH-DA staining, DRP1 expression in lung tissue and BEAS-2B cells was detected by immunohistochemistry and immunofluorescence, and the DRP1-NLRP3 pathway was analyzed by immunoblotting. Results FN treatment could effectively ameliorate the symptoms of asthmatic mouse model, including reducing eosinophil accumulation, airway collagen deposition, decreasing Th2 cytokine and IgE levels, reducing ROS and MDA production, increasing SOD and CAT activities, and regulating DRP1-NLRP3 pathway-related protein expression, thereby relieving inflammation. Conclusion FN ameliorates airway inflammation in asthma by regulating DRP1-NLRP3 pathway.

CT-Based Weighted Radiomic Score Predicts Tumor Response to Immunotherapy in Non-Small Cell Lung Cancer / 中国医学科学院学报

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.

Effects of traditional korean medicine Lurong Dabu Decoction on TLR4/WNT-5A signaling pathway in guinea pigs with cough variant asthma / 中国药理学通报

Aim To discuss the mechanism of Lurong Dabu Decoction on cough variant asthma. Methods Guinea pigs were divided into normal group(CON), model group(OVA), Lurong Dabu Decoction high-dose group(HIGH),low-dose group(LOW), and dexamethasone group(DEX)at random. The CVA model was established by smoking plus injection of OVA, aluminum hydroxide solution and nebulized inhalation to stimulate cough. Gguinea pigs were dissected 24 hours after the last challenge to obtain alveolar lavage fluid(BALF)and lung tissues. Immunoadsorption(ELISA)method was applied to detect the types of inflammatory cells and the content of inflammatory cytokines in BALF; HE and Masson staining of the middle lobe of the left lung were used to observe the pathological changes in lung tissues; immunohistochemical staining was used to observe TLR4 and WNT-5A protein expression and distribution of lung tissues; the protein extracted from the upper lobe of the left lung was used to measure the level of TLR4 and WNT-5A protein in lung tissues by Western blot; immunofluorescence was employed to measure the fluorescence intensity of TLR4 and WNT-5A in lung tissues; flow cytometry was used to detect IL-4 and IFN-γ in guinea pig lung tissues. Results Lurong Dabu Decoction could improve guinea pig airway inflammation, inhibit collagen fiber deposition, reduce the content of IL-4, IL-5, and IL-13 in BALF, and inhibit the protein expression of TLR4 and WNT-5A in lung tissues and increase IFN-γ levels in lung tissues while decreasing IL-4 levels. Conclusion Lurong Dabu Decoction may inhibit the occurrence of CVA through TLR4/WNT-5A signaling pathway.

Panax notoginseng saponin Rl attenuates allergic rhinitis through AMPK/DRP1 mediated mitochondrial fission / 中国药理学通报

Aim To investigate whether notoginsenoside Rl (PNS-R1) alleviates allergic rhinitis (AR) through AMP-activated protein kinase (AMPK)/mitochondrial fission critical protein (DRP1) -mediated mitochondrial fission. Methods Different doses of PNSRl were used to treat ovalbumin (OVA) -induced AR model mice,and the inhibitory effect of PNS-R1 on AR was investigated by observing allergic symptoms such as nasal rubbing and sneezing, as well as HE staining of nasal tissues. Serum IgE levels and nasal lavage fluid (NLF) inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA) and apoptosis-related proteins were detected by Western blot. In vitro human nasal epithelial cells (HNEpC) were stimulated with IL-13 to observe apoptosis, mitochondrial membrane potential, cellular ROS and mitochondrial ROS production, as well as the expression levels of AMPK/DRP1, expression levels of the TXNIP/NLRP3 inflammasomes and the translocation of DRP1. Results PNS-R1 attenuated allergic symptoms in AR mice, HE staining reduced inflammatory cells and reduced the levels of OVA-specific IgE in serum, and the levels of IL-4, IL-6, and IL-8 in NLF. PNS-R1 attenuated the apoptosis and ROS production of nasal epithelial cells in AR. In vitro PNS-R1 could up-regulate mitochondrial membrane potential after IL-13 stimulation, reduce ROS and mtROS production, the proportion of apoptotic positive cells, and reduce cleaved caspase-3, Bax, and up-regulate Bcl-2 expression, down-regulate DRP1 phosphorylation (Ser 616) and DRP1 translocation at the mitochondrial membrane in an AMPK-dependent manner, reducing TXNIP/NLRP3 expression. Conclusions PNS-R1 can protect mitochondrial integrity by inhibiting the AMPK/DRP1 signaling axis and its subsequent TXNIP/NLRP3 signaling axis,thereby alleviating rhinitis in AR mice.

JTE-013 mediates RhoA/ROCKl/Drpl signaling axis regulating mitochondrial damage and apoptosis to alleviate allergic rhinitis / 中国药理学通报

Aim To investigate the protective effect and mechanism of JTE-013 on allergic rhinitis (AR) by regulating mitochondrial injury and apoptosis through RhoA/ROCKl/Drpl pathway. Methods AR model was established by ovalbumin (OVA) in mice. Nasal tissue sections were then stained with HE, TUNEL and DHE. Western blot assay. In vitro, human nasal epithelial cells (HNEpCs) were stimulated with human recombinant interleukin-13 (IL-13), and the effects of JTE-013 and Y27632-related protein expression were detected by Western blot. Immunofluorescence was used to observe the effects of JTE-013 and Y 27632 on total ROS, mitochondrial membrane potential and mitochondrial ROS generation, Drpl translocation and Cyt-c expression in cells. Results JTE-013 reduced the frequency of nose rubbing and sneezing, reduced nasal mucosal thickening and decreased eosinophil infiltration in AR mice. TUNEL and DHE staining results suggested that JTE-013 could inhibit apoptosis and reduce ROS expression in mouse nasal epithelial cells. Western blot showed that both JTE-013 and Y 27632 could significantly reduce RhoA, ROCK1, Drpl and p-Drpl(616), inhibit the expression of apoptotic proteins Bax, cleaved-caspase-3, Cyt-c, cleavedcaspase-9 and up-regulate the expression of p-Drpl (637) and Bcl-2. Immunofluorescence showed that inhibitors of JTE-013 or ROCK1 almost blocked IL-13mediated increase in ROS and mtROS production, inhibited decrease in mitochondrial membrane potential, and blocked Cyt-c expression and Drpl translocation in nasal mucosal epithelial cells. Conclusion JTE-013 can regulate the morphology and function of mitochondria by inhibiting RhoA/ROCKl/Drpl signaling axis, thereby alleviating nasal epithelial cell inflammation in mice with allergic rhinitis.

Polydatin alleviates allergic rhinitis by regulating PINK1-Parkin-mediated mitophagy / 中国药理学通报

Objective To investigate the protective effect and mechanism of polydatin ( PD) on allergic rhinitis (AH) by regulating mitophagy through PINK1- Parkin signaling pathway, and to provide a new target for clinical treatment of AH.Methods Thirty-two BALB/c murine were randomly divided into 4 groups: control group, OVA group, PD low-dose (30 mg • kg 1 ) and high-dose ( 45 mg • kg 1 ) treatment groups.At the end of modeling, the total number of sneezing and nasal nibbing of murine was recorded.HE staining was used to observe the morphology of na- sal mucosal epithelium and eosinophil infiltration.Western blot was used to detect the expression of P1NK1 , Parkin, TOM20 and mitochondrial apoptosis- related proteins Bax, Bcl-2, caspase-3, cleaved- caspase-3 and Cytochrome C.Hie expression of P1NK1 and cleaved-caspase-3 in nasal epithelial cells (HNEpC) was observed by immunofluorescence.Re¬sults The frequency of sneezing and nasal rubbing movements was significantly increased, the nasal mu¬cosa epithelium was thickened, and eosinophils were accumulated in AH murine , these results were reversed after PD treatment.Western blot results shower] that signaling proteins PINK1/Parkin anrl pro-apoptotie pro¬teins, including Bax, caspase-3, cleaved-caspase-3 and Cytochrome C were significantly overexpressed, the expression of TOM20 and Bcl-2 was decreased in OVA group, and PD up-regulated the levels of P1NK1 , Parkin, as well as Bcl-2 and inhibited the expression of TDM20 and pro-apoptotic proteins, while after pre- treatment with mitochondrial division inhibitor 1 ( Mdi- vi-1 ) , the expression of P1NK1 and Parkin was re¬duced , the expression of TOM20 was increased, while PD treatment did not significantly affect this effect.From the immunofluorescence results, it can be seen that the level of P1NK1 was increased after IL-13 stim¬ulation of HNEpCs compared with the control group, and PD further up-regulated the expression of P1NK1 , which was suppressed after pretreatment with Mdivi-1 , while PD did not change this phenomenon.Western blot results for P1NK1 and cleaved-caspase-3 were con¬firmed by immunofluorescence.Conclusion PD may activate mitophagy through the P1NK1 -Parkin signaling pathway, thereby protecting against AR.

Feasibility study of chest ultra-low dose CT with deep learning reconstruction for lung cancer screening / 中华放射学杂志

Objective:To investigate the feasibility of chest ultra-low dose CT (ULDCT) using deep learning reconstruction (DLR) for lung cancer screening, and to compare its image quality and nodule detection rate with ULDCT iterative reconstruction (Hybrid IR) and conventional dose CT (RDCT) Hybrid IR.Methods:The patients who underwent chest CT examination for pulmonary nodules in Peking Union Medical College Hospital from October 2020 to March 2021 were prospectively included and underwent chest RDCT (120 kVp, automatic tube current), followed by ULDCT (100 kVp, 20 mA). The RDCT images were reconstructed with Hybrid IR (adaptive iterative dose reduction 3D,AIDR 3D), and ULDCT was reconstructed with AIDR3D and DLR. Radiation dose parameters and nodule numbers were recorded. Image quality was assessed using objective noise, signal-to-noise ratio (SNR) of the main trachea and left upper lobe, subjective image scores of the lung and nodules. Subjective scores were scored by 2 experienced radiologists on a Likert 5-point scale. The difference of radiation dose was compared with paired t-test between ULDCT and RDCT.The differences of quantitative indexes, objective image noise and subjective scores of the three reconstruction methods were compared with one-way analysis of variance or Friedman test. Results:Forty-five patients were enrolled, including 17 males and 28 females, aged from 32 to 74 (55±11) years. The radiation dose of ULDCT was (0.17±0.01) mSv, which was significantly lower than that of RDCT [(1.35±0.41) mSv, t=15.46, P<0.001]. There were significant differences in the image noise and SNR in the trachea and lung parenchyma and in the CT value of the trachea among ULDCT-AICE, ULDCT-AIDR 3D and RDCT-AIDR 3D images ( P<0.05). Image noise in the trachea and lung parenchyma and CT value in the trachea of ULDCT-AICE were significantly lower than those of ULDCT-AIDR 3D ( P<0.05) and comparable to RDCT-AIDR 3D ( P>0.05). There were significant differences in subjective image scores of the lung and nodules among ULDCT-AICE, ULDCT-AIDR 3D and RDCT-AIDR 3D images (χ2=50.57,117.20, P<0.001). Subjective image scores of the lung and nodules for ULDCT-AICE were significantly higher than those of ULDCT-AIDR 3D ( P<0.05), and non-inferior to RDCT-ADIR 3D ( P>0.05). All 72 clinically significant nodules detected on RDCT-ADIR 3D were also noted on ULDCT-AICE and ULDCT-AIDR 3D images. Conclusions:Chest ULDCT using DLR can significantly reduce the radiation dose, and compared with Hybrid IR, it can effectively reduce the image noise and improve SNR, and display the pulmonary nodules well. The image quality and nodule detection are not inferior to RDCT Hybrid IR routinely used in clinical practice.

The clinical value of deep learning reconstruction in low-dose CT pulmonary angiography / 中华放射学杂志

Objective:To explore the effect of deep learning reconstruction (DLR) on radiation dosage reduction and image quality of CTPA compared with hybrid iterative reconstruction (HIR).Methods:A total of 100 patients with suspected pulmonary embolism (APE) or indications for CTPA due to other pulmonary artery diseases in Peking Union Medical College Hospital from December 2020 to April 2021 were prospectively enrolled and divided into HIR group and DLR group according to block randomization, with 50 cases in each group. The patient′s gender, age and body mass index (BMI) were recorded. HIR group and DLR group underwent standard deviation (SD)=8.8 and SD=15 CTPA protocols in combination with HIR and DLR algorithm respectively. Other scanning parameters and contrast medium injection plan were the same. The effective dose (ED) and size-specific dose estimate (SSDE) were calculated. Regions of interest (ROIs) were drawn in the lumen of Grade 1-3 pulmonary arteries and bilateral paravertebral muscles. The corresponding CT and SD values were recorded to acquire signal to noise ratio (SNR) and contrast noise ratio (CNR). Based on a double-blind method, two radiologists evaluated the subjective noise, visualization of pulmonary arteries, and diagnostic confidence of the two groups by 5-point Likert scales. The inconsistent results were judged comprehensively by the third radiologist. Independent samples t-test was used to compare the demographic data, radiation dosage and quantitative image quality of the two groups. Mann-Whitney U test was used to compare the subjective noise, visualization of pulmonary arteries and diagnostic confidence between the two groups. Linear weighted Kappa coefficient was calculated to analyze the consistency of the qualitative scores between the two radiologists. Results:There were no significant differences in gender, age and BMI between the two groups ( P>0.05). The CT values of Grade1-3 pulmonary arteries and paravertebral muscle had no significant differences ( P>0.05). Compared with HIR group, the ED and SSDE in DLR group decreased by about 35% to 1.3 mSv and 4.20 mGy respectively, while the SNR (30±5) and CNR (26±5) of CTPA images were higher in DLR group than those in HIR group (23±5 and 20±5, with t=-6.60 and -5.90, respectively, both P<0.001). The subjective noise score was higher in DLR group than that in HIR group ( Z=-7.34, P<0.001). In addition, two radiologists showed excellent interobserver agreement in DLR group (Kappa=0.847, 95%CI 0.553-1.000). No significant differences were found in visualization of pulmonary arteries and diagnostic confidence between the two groups ( P>0.05). Conclusion:DLR further reduced the radiation dosage and improved the image quality of CTPA, with no detriment to diagnostic confidence. Thus DLR is worthy of clinical promotion.

Application value of deep learning reconstruction to improve image quality of low-dose chest CT / 中华放射学杂志

Objective:To evaluate the effectiveness of deep learning reconstruction (DLR) compared with hybrid iterative reconstruction (Hybrid IR) in improving the image quality in chest low-dose CT (LDCT).Methods:Seventy-seven patients who underwent LDCT scan for physical examination or regular follow-up in Peking Union Medical College Hospital from October 2020 to March 2021 were retrospectively included. The LDCT images were reconstructed with Hybrid IR at standard level (Hybrid IR Stand) and DLR at standard and strong level (DLR Stand and DLR Strong). Regions of interest were placed on pulmonary lobe, aorta, subscapularis muscle and axillary fat to measure the CT value and image noise. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated. Subjective image quality was evaluated using Likert 5-score method by two experienced radiologists. The number and features of ground-glass nodule (GGN) were also assessed. If the scores of the two radiologists were inconsistent, the score was determined by the third radiologist. The objective and subjective image evaluation were compared using the Kruskal-Wallis test, and the Bonferroni test was used for multiple comparisons within the group.Results:Among Hybrid IR Stand, DLR Stand and DLR Strong images, the CT value of pulmonary lobe, aorta, subscapularis muscle and axillary fat had no significant differences (all P>0.05), but the image noise and SNR of pulmonary lobe, aorta, subscapularis muscle and axillary fat had significant differences(all P<0.05), and the CNR of images had significant difference( P<0.05), too. The CNR of Hybrid IR Stand images, DLR stand images and DLR strong images were 0.71 (0.49, 0.88), 1.06 (0.78, 1.32) and 1.14 (0.84, 1.48), respectively. Compared with Hybrid IR images, DLR images had lower objective and subjective image noise,higher SNR and CNR (all P<0.05). The scores of DLR images were superior to Hybrid IR images in identifying lung fissures, pulmonary vessels, trachea and bronchi, lymph nodes, pleura, pericardium and GGN (all P<0.05). Conclusions:DLR significantly reduced the image noise, and DLR images were superior to Hybrid IR images in identifying GGN in chest LDCT while maintaining superior image quality at relatively low radiation dose levels. Thus DLR images can improve the safety of lung cancer screening and pulmonary nodule follow-up by CT.

Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

Astragalin inhibits airway inflammation in asthma through NOX2/ROS/NF-κB signaling pathway / 中国药理学通报

Aim To investigate the effect of astragalin (AG) on airway inflammation in asthmatic mice and its mechanism. Methods Fifty SPF male mice were randomly divided into normal group, asthma model group, and astragalin low (AG25), medium (AG50), and high (AG100) dose groups. A mouse model of asthma was prepared by egg albumin inhalation, the number of cells was counted by Diff-Quik staining after collecting bronchoalveolar lavage fluid (BALF), and IL4, 5, and 13 levels in BALF were measured by ELISA. The inflammatory changes in mouse lung tissues were observed using HE staining. Reactive oxygen species (ROS) levels were measured using a DCFH-DA probe, and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by colorimetry. IL-4, IL-5, IL-13, NOX2, p47phox, p-NF-κBp65, NF-κBp65, IκBα, p-IκBα and β-actin expressions in lung tissues were detected by Western blot. Results AG significantly reduced the number of inflammatory cells and total cells in BALF, decreased IL-4, IL-5, and IL-13 contents in BALF and lung tissues, and reduced inflammatory cell infiltration in lung tissues. AG inhibited nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and p47phox expression, decreased ROS levels and MDA levels, increased SOD activity, and inhibited IκBα and NF-κBp65 phosphorylation. Conclusion AG attenuates airway inflammation in asthma by modulating the oxidative stress response through the NOX2/ROS/NF-κB signaling pathway.

Arctigenin attenuates airway inflammation in asthmatic mice via SIRT1/NLRP3 pathway / 中国药理学通报

Aim To investigate the efficacy of arctigenin on airway inflammation in a mouse model of asthma and the mechanism related to the SIRT1/NLRP3 signaling pathway. Methods Forty female BALB/c mice of clean grade were selected and divided into control group, OVA model group and ATG group (5, 10 and 20 mg · kg

Glaucocalyxin A attenuates allergic responses by inhibiting mast cell degranulation through HMGB1/TLR4/NF-κB signaling pathways / 药学学报

The study is to investigate the effect of glaucocalyxin A (GLA) on mast cell-mediated anaphylaxis. The animal welfare and experimental process of this experiment followed the regulations of the Animal Ethics Committee of Yanbian University. BALB/c mice were used in the animal experiment and randomly divided into five groups, control group, model group, and GLA low, medium, and high dose groups (10, 20, and 40 mg·kg-1). Mice were sensitized by intradermal injection of anti-dinitrophenyl-immunoglobulin E (DNP-IgE) into the ears and challenged with a mixture of DNP-human serum albumin (HSA) and 4% evans blue into the tail veins to prepare an animal skin passive cutaneous anaphylaxis (PCA) model, which was collected from both ears for measurement of dye staining and histology. Rat peritoneal mast cells (RPMCs) were used in the cell experiment and divided into control, IgE + antigen (Ag), and IgE + Ag + GLA groups to determine histamine release as well as calcium influx levels. High-affinity IgE receptor (FcεRI)-mediated signaling pathway proteins and HMGB1/TLR4/NF-κB (high mobility group box 1/toll like receptor 4/nuclear transcription factor kappa B) signaling proteins were detected by Western blot. The results of animal experiments suggest that GLA inhibits PCA, reduces evans blue dye exudation, and reduces ear inflammation and ear thickness in mice. The results of cellular experiments suggested that GLA could reduce histamine release and calcium influx, and inhibit tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-13, and IL-1β production; Western blot results showed that GLA inhibited FcεRI-mediated phosphorylation levels of spleen tyrosine kinase (Syk), Lck/Yes novel tyrosine kinase (Lyn), tyrosine kinase Fyn (Fyn), growth-factor receptor-bound protein 2 (Gab2), and phospholipase C (PLC) γ1, while GLA inhibited HMGB1/TLR4 signaling pathway to limit NF-κB p65 nuclear metastasis. The results indicate that GLA inhibits mast cell degranulation and attenuates allergic inflammation through the HMGB1/TLR4/NF-κB signaling pathway.

Mental health status of primary school students during the coronavirus disease 2019 epidemic and its influencing factors / 中国当代儿科杂志

OBJECTIVE@#To study the mental health status of primary school students and the factors influencing the mental health status during the coronavirus disease 2019 (COVID-19) epidemic.@*METHODS@#Online questionnaire surveys were conducted among 3 600 primary school students aged 6-12 years in Jilin Province, China in April, 2020 (during the epidemic) and 3 089 primary school students in September, 2020 (during the regular epidemic prevention and control). The general information and the data related to the Mental Health Scale for Child and Adolescent were collected by the questionnaire surveys. The multivariate logistic regression analysis was used to evaluate the factors influencing the mental health status of the students during the epidemic.@*RESULTS@#The students during the epidemic had a significantly poorer mental health status in the emotional experience and volitional behavior than those during the regular epidemic prevention and control (@*CONCLUSIONS@#The COVID-19 epidemic has a certain impact on emotional experience and volitional behavior of primary school students. During the epidemic, particular attention should be paid to the mental health of primary school students, especially girls, younger students, and students from single-parent families, extended families or families with impatient parents and improper parental education.

Osimertinib Re-challenge for EGFR-mutant NSCLC after Osimertinib-induced Interstitial Lung Disease: A Case Report / 中国肺癌杂志

Osimertinib-induced interstitial lung disease (ILD) is an uncommon, but fatal pulmonary toxicity in some patients. We report a case of a 64-year-old male with stage IV adeno-non-small cell lung cancer (NSCLC) harboring an exon 19 deletion in the epidermal growth factor receptor (EGFR) treated with osimertinib 80 mg/d for first-line targeted therapy. On day 60 after initiating treatment of osimertinib, the patient developed ILD. Osimertinib was discontinued immediately and oral prednisone 60 mg/d was initiated, ILD improved within 13 d. After balancing the risk and benefit, osimertinib was restarted concurrently with prednisone. The patient showed neither disease progression nor a recurrence of ILD for more than 16 months. Based on our case and literature review, retreatment with osimertinib under steroid coverage could be considered as an effective treatment option after careful risk-benefit assessment for patients with EGFR-mutant NSCLC.
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Epidemiologic Features, Radiological Findings andClinical Outcomes of 19 Patients with COVID-19in a Single Center in Beijing, China / 中国医学科学杂志(英文版)

ObjectiveTo describe the epidemiologic, clinical, laboratory, and radiological characteristics and prognoses of COVID-19 confirmed patients in a single center in Beijing, China. Methods The study retrospectively included 19 patients with nucleic acid-confirmed SARS-CoV-2 infection at our hospital from January 20 to March 5, 2020. The final follow-up date was March 14, 2020. The epidemiologic and clinical information was obtained through direct communication with the patients or their family members. Laboratory results retrieved from medical records and radiological images were analyzed both qualitatively by two senior chest radiologists as well as quantitatively via an artificial intelligence software. Results We identified 5 family clusters (13/19, 68.4%) from the study cohort. All cases had good clinical prognoses and were either mild (3/19) or moderate (16/19) clinical types. Fever (15/19, 78.9%) and dry cough (11/19, 57.9%) were common symptoms. Two patients received negative results for more than three consecutive viral nucleic acid tests. The longest interval between an initial CT abnormal finding and a confirmed diagnosis was 30 days. One patient's nucleic acid test turned positive on the follow-up examination after discharge. The presence of radiological abnormalities was non-specific for the diagnosis of COVID-19. Conclusions COVID-19 patients with mild or no clinical symptoms are common in Beijing, China. Radiological abnormalities are mostly non-specific and massive CT examinations for COVID-19 screening should be avoided. Analyses of the contact histories of diagnosed cases in combination with clinical, radiological and laboratory findings are crucial for the early detection of COVID-19. Close monitoring after discharge is also recommended.

Effect of transcutaneous electrical acupoint stimulation on labor analgesia / 中国针灸

OBJECTIVE@#To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on labor pain.@*METHODS@#A total of 151 primiparas who were vaginal delivery were randomized into a TEAS group (76 cases) and a peridural group (75 cases). In the peridural group, peridural blockage was applied to analgesia. In the TEAS group, TEAS was applied at Hegu (LI 4)，Neiguan (PC 6), Jiaji T~L (EX-B 2) and Ciliao (BL 32), disperse-dense wave (2 Hz/100 Hz), 15-50 mA in current intensity. The analgesic time was from 3 cm to completely opening of cervix. The visual analogue scale (VAS) scores were observed before analgesia, after 30, 60, 120 min of analgesia in the two groups. The time of different stages of labor, usage rate of oxytocin, incidence rate of adverse reaction and amount of postpartum hemorrhage were recorded. The newborn's 1 and 5 min Apgar scores were evaluated.@*RESULTS@#The VAS scores showed a downward trend in the two groups after analgesia (0.05). The usage rate of oxytocin and incidence rate of adverse reaction in the TEAS group were 9.2% (7/76) and 2.6% (2/76), which were lower than 34.7% (26/75) and 18.7% (14/75) in the peridural group (0.05).@*CONCLUSION@#The analgesic effect of TEAS is inferior to peridural blockage, but TEAS could relieve labor pain to the tolerance, shorten the time of active phase on the first stage and second stage of labor and reduce the use of oxytocin, has mild adverse reaction.

Chest High-resolution Computed Tomography Imaging Features of Lung Involvement in Rheumatoid Arthritis / 中国医学科学院学报

To explore the chest high-resolution computed tomography (HRCT) features in patients with rheumatoid arthritis (RA) complicated with pulmonary involvement. Totally 161 patients with RA with lung involvement were collected from June 2014 to May 2018. The chest HRCT findings were retrospectively analyzed. According to the imaging features as well as the results of history taking,pulmonary function test,pathology,and bronchoalveolar lavage fluid test,RA-related lung diseases (RA-LD) were classified and their clinical characteristics were compared. These 161 RA-LD patients (56 males and 105 females) whose mean age at diagnosis was (60.7±12.8) years (14-85 years) included 87 cases of usual interstitial pneumonia (UIP) (including 16 cases of possible UIP),44 cases of non-specific interstitial pneumonia (NSIP),10 cases of organizing pneumonia,7 cases of lymphocytic interstitial pneumonia,9 cases of small airway disease (SAD) (including 8 cases of bronchiolitis obliterans and 1 case of follicular bronchiolitis),and 4 other lung manifestations (including 3 cases of diffuse alveolar hemorrhage and 1 case of rheumatoid nodules). The UIP group had the oldest average age [(63.3±12.1) years old] and the highest smoking rate (41.4%). The SAD group had the youngest average age [(54.7±15.1) years old] and there was no smoking history. There were significant differences between these two groups (=0.020,<0.001). Seventy patients (43.5%) with RA-LD were complicated with pleural lesions. RA involving the lung is common and has varied imaging manifestations,with interstitial lung diseases (mainly UIP and NSIP) being the most important manifestations. RA patients should undergo lung HRCT as early as possible to identify the lung involvement and related types.

Preliminary Study on Clinical Features and CT Findings of Common-type Coronavirus Disease 2019 Patients in Peking Union Medical College Hospital / 中国医学科学院学报

To summarize the clinical characteristics and chest CT findings of coronavirus disease 2019(COVID-19)patients in Peking Union Medical College Hospital(PUMCH). A total of 13 patients with COVID-19 confirmed at PUMCH from January 20 to February 6,2020 were selected as the research subjects.Their epidemiological histories,clinical characteristics,laboratory tests,and chest CT findings were analyzed retrospectively.The location,distribution,density,and other accompanying signs of abnormal lung CT lesions were recorded,and the clinical types of these patients were assessed. The clinical type was "common type" in all these 13 patients aged(46.8±14.7)years(range:27-68 years).Ten patients had a travel history to Wuhan or direct contact with patients from Wuhan,2 cases had recent travel histories,and 1 case had a travel history to Beijing suburb.The white blood cell(WBC)count was normal or decreased in 92.3% of the patients and the lymphocyte count decreased in 15.4% of the patients.Twelve patients(92.3%)had a fever,among whom 11 patients were admitted due to fever and 2 patients(15.4%)had low fever.Eight patients(61.5%)had dry cough.The CT findings in these 13 patients were all abnormal.The lesions were mainly distributed along the bronchi and under the pleura.The lesions were relatively limited in 8 patients(affecting 1-3 lobes,predominantly in the right or left lower lobe),and diffuse multiple lesions of bilateral lungs were seen in 5 patients.The CT findings mainly included ground glass opacities(GGOs)(=10,76.9%),focal consolidation within GGOs(=7,53.8%),thickened vascular bundle passing through the lesions(=10,76.9%),bronchial wall thickening(=12,92.3%),air bronchogram(=10,76.9%),vacuole signs in the lesions(=7,53.8%),fine reticulation and interlobular septal thickening(=3,23.1%),reversed halo-sign(=2,15.4%),crazy-paving pattern(=2,15.4%),and pleural effusion(=2,15.4%). Most of our patients diagnosed with COVID-19 at PUMCH had a travel history to Wuhan or direct contact with patients from Wuhan.The first symptoms of COVID-19 mainly include fever and dry cough,along with normal or reduced counts of WBC and lymphocytes.CT may reveal that the lesions distribute along the bronchi and under the pleura;they are typically localized GGOs in the early stage but can become multiple GGOs and infiltrative consolidation in both lungs in the advanced stage.Scattered vacuole signs may be visible inside the lesions in some patients.