2. Mechanism of action of formononetin in alleviating allergic asthma through DRP1-NLRP3 signaling pathway
Mu CHEN ; Qiao-Yun BAI ; Yi-Lan SONG ; Jiao CHEN ; Yong-De JIN ; Guang-Hai YAN ; Jiao CHEN ; Yong-De JIN ; Qiao-Yun BAI ; Yi-Lan SONG ; Guang-Hai YAN
Chinese Pharmacological Bulletin 2024;40(3):529-536
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.
3.Chinese expert consensus on transcatheter tricuspid valve intervention therapy
Chinese College of Cardiovascular Physicians Structural Cardiology Group ; House Heart CHINA ; Wen-Zhi PAN ; Guang-Yuan SONG ; Da-Xin ZHOU ; Yong-Jian WU
Chinese Journal of Interventional Cardiology 2024;32(10):551-561
Tricuspid regurgitation(TR)is a common heart valve disease traditionally treated with surgery,which is invasive and high-risk.Recently,transcatheter tricuspid valve intervention(TTVI)technology has achieved major breakthroughs.It is being promoted internationally and several expert consensus documents have been launched abroad.However,in China,there is still a lack of consensus documents in this regard.In order to promote the safe,standardized and healthy development of this technology,this expert consensus is specially compiled.This consensus will introduce anatomy,epidemiology,classification and pathogenesis of TR,the traditional treatment and TTVI,preoperative evaluation and clinical efficacy endpoints.We sort out ten core viewpoints so that readers can quickly grasp the essence of the consensus.
4.2024 expert consensus on clinical pathway for transcatheter aortic valve replacement in China
Structural Cardiology Committee of Cardiovascular Physicians Branch,Chinese Medical Doctor Association ; Asia Pacific Structural Heart Disease Club ; Guang-Yuan SONG ; Wen-Zhi PAN ; Da-Xin ZHOU ; Yong-Jian WU
Chinese Journal of Interventional Cardiology 2024;32(11):601-617
Transcatheter aortic valve replacement(TAVR)has reached maturity and has entered a stage of steady and stable development in China.From 2017 to 2023,the number of centers conducting TAVR in China has increased from less than 10 to over 600,and the annual implantation volume has increased from hundreds to over 10 000.The 2018 and 2021 editions of the"Expert Consensus on Clinical Pathway for Transcatheter Aortic Valve Replacement in China"played a crucial guiding role during the golden period of TAVR development in China.With significant progress in evidence-based practice,clinical experience,guideline updates,device development,and procedure technique improvements in the TAVR field,especially the important advances in technologies developed from China,protocol optimization based on Chinese clinical practices,it is necessary to update the previous clinical pathway consensus.The new version of the clinical pathway expert consensus has updated the standard procedures for preoperative clinical assessment,perioperative imaging evaluation,standardized procedural processes,comprehensive perioperative management,and postoperative rehabilitation follow-up for TAVR patients.This update aims to further promote the healthy and standardized development of TAVR technology in China and to steadily enhance the medical and scientific research capabilities with this therapeutic technology.
5. JTE-013 mediates RhoA/ROCKl/Drpl signaling axis regulating mitochondrial damage and apoptosis to alleviate allergic rhinitis
Jiao CHEN ; Long-Zhu DAI ; Mu CHEN ; Yi-Lan SONG ; Guang-Hai YAN ; Chong-Yang WANG ; Yong-De JIN ; Jiao CHEN ; Mu CHEN ; Yong-De JIN ; Long-Zhu DAI ; Yi-Lan SONG ; Guang-Hai YAN ; Chong-Yang WANG
Chinese Pharmacological Bulletin 2023;39(9):1638-1647
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.
6. Panax notoginseng saponin Rl attenuates allergic rhinitis through AMPK/DRP1 mediated mitochondrial fission
Ya-Lin ZHANG ; Chong-Yang WANG ; Si-Qi LIU ; Hai-Nan JIN ; Yi-Lan SONG ; Guang-Hai YAN ; Yong-De JIN ; Ya-Lin ZHANG ; Si-Qi LIU ; Hai-Nan JIN ; Yong-De JIN ; Chong-Yang WANG ; Yi-Lan SONG ; Guang-Hai YAN
Chinese Pharmacological Bulletin 2023;39(3):512-519
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.
7.Quick guideline for diagnosis and treatment of novel coronavirus Omicron variant infection
Guang CHEN ; Tao CHEN ; Sainan SHU ; Xiaojing WANG ; Ke MA ; Di WU ; Hongwu WANG ; Yan LIU ; Wei GUO ; Meifang HAN ; Jianxin SONG ; Tonglin LIU ; Shusheng LI ; Jianping ZHAO ; Yuancheng HUANG ; Yong XIONG ; Zuojiong GONG ; Qiaoxia TONG ; Jiazhi LIAO ; Feng FANG ; Xiaoping LUO ; Qin NING
Chinese Journal of Clinical Infectious Diseases 2023;16(1):26-32
Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.
8.Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study.
Fang JIN ; Yu CHEN ; Yi-Xun LIU ; Su-Ying WU ; Chao-Ce FANG ; Yong-Fang ZHANG ; Lu ZHENG ; Li-Fang ZHANG ; Xiao-Dong SONG ; Hong XIA ; Er-Ming CHEN ; Xiao-Qin RAO ; Guang-Quan CHEN ; Qiong YI ; Yan HU ; Lang JIANG ; Jing LI ; Qing-Wei PANG ; Chong YOU ; Bi-Xia CHENG ; Zhang-Hua TAN ; Ya-Juan TAN ; Ding ZHANG ; Tie-Sheng YU ; Jian RAO ; Yi-Dan LIANG ; Shi-Wen XIA
Chinese Journal of Contemporary Pediatrics 2023;25(7):697-704
OBJECTIVES:
To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.
METHODS:
A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.
RESULTS:
Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.
CONCLUSIONS
The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn
;
Humans
;
Male
;
Pregnancy
;
Female
;
Nomograms
;
Retrospective Studies
;
Cesarean Section
;
Risk Factors
;
Asphyxia Neonatorum/etiology*
9.Analysis of three minimally invasive methods in the treatment of the fifth metacarpal neck fracture.
Hui-Min ZHAO ; Guang-Yuan ZHAO ; Yong-Sheng SONG
China Journal of Orthopaedics and Traumatology 2023;36(7):601-606
OBJECTIVE:
To explore the effective method of applying Chinese medicine manipulative repositioning Kirschner wire fixation for minimally invasive treatment of fractures of the neck of the fifth metacarpal.
METHODS:
From January 2018 to November 2021, 90 patients with closed fractures of the neck of the fifth metacarpal bone were treated minimally invasively with closed repositioning Kirschner wires, all fractures AO type was type A. All patients were divided into three groups according to the mode of internal fixation involving 30 cases in the crossed Kirschner's wire group, 30 cases in the transverse Kirschner's wire group, 30 patients in the intramedullary Kirschner's wire group. By comparison, gender, age, disease duration, and preoperative neck-stem angle were not significant. The postoperative fifth metacarpal neck-stem angles, postoperative fifth metacarpophalangeal joint flexion mobility and fifth metacarpophalangeal joint extension hyperextension angles were compared among three groups. The overall clinical efficacy was evaluated according to the patient outcomes of surgery-hand/arm(POS-Hand/Arm) scoring system.
RESULTS:
All patients had 12-month follow-up and achieved bony union without malunion. There was no significant difference in the 5th metacarpal neck-stem angle, the fifth metacarpophalangeal joint flexion angle and the fifth metacarpophalangeal joint extension hyperextension angles among three groups at 12 months after surgery(P>0.05). There was no significant difference in physical activity and symptom scores in POS-Hand/Arm scores at 12 months after surgery(P>0.05), psychological status and aesthetic score among three groups(P<0.05) and between cross and transverse Kirschner wire groups(P>0.05). The three POS-Hand/Arm total scores were statistically different(P<0.05), between the crossed and transverse(P>0.05), and the intramedullary group had the highest POS-Hand/Arm scores.
CONCLUSION
All three techniques of Kristener's wire fixation could achieve minimally invasive treatment, and patients have need for cosmetic and early activity, and the author recommend minimally invasive intramedullary fixation with manipulative repositioned Kristen wires as the preferred procedure.
10.Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study
Lu WANG ; Ying-Jie DAI ; Yu CUI ; Hong ZHANG ; Chang-Hao JIANG ; Ying-Jie DUAN ; Yong ZHAO ; Ye-Fang FENG ; Shi-Mei GENG ; Zai-Hui ZHANG ; Jiang LU ; Ping ZHANG ; Li-Wei ZHAO ; Hang ZHAO ; Yu-Tong MA ; Cheng-Guang SONG ; Yi ZHANG ; Hui-Sheng CHEN
Journal of Stroke 2023;25(3):371-377
Background:
and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset.
Methods:
In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH).
Results:
Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group.
Conclusion
This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

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