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Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1726-1741页

作者： Yanjiang Xing Yangfeng Hou Tianfei Fan Ran Gao Xiaohang Feng Bolun Li Junling Pang Wenjun Guo Ting Shu Jinqiu Li Jie Yang Qilong Mao Ya Luo Xianmei Qi Peiran Yang chaoyang liang Hongmei Zhao Wenhui Chen Jing Wang Chen Wang State Key Laboratory of Respiratory Health and Multimorbidity Institute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005China Department of Lung Transplantation National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina–Japan Friendship HospitalInstitute of Respiratory MedicineChinese Academy of Medical SciencesBeijing 100029China Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300051China The State Key Laboratory of Complex Severeand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610044China

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

关键词： Phosphodiesterase 4B Pulmonary hypertension Endothelial-to-mesenchymal transition

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Modification of POSS and their tribological properties and resistant to space atomic oxygen irradiation as lubricant additive of multialkylated cyclopentanes

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Friction 2024年第5期12卷 884-896页

作者： Xingwei WANG chaoyang ZHANG Chen ZHAO Yijing liang Ming ZHANG Wufang YANG Bo YU Qiangliang YU Meirong CAI Feng ZHOU Weimin LIU State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou730000China Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing Yantai264000China

Developing functional additive resistant to space atomic oxygen(AO)irradiation through simple molecular design and chemical synthesis to enhance the lubricating performance of multialkylated cyclopentanes(MACs)oil is a significant challenge.Herein,sulfur-containing polyhedral oligomere silsesquioxane(POSS)were synthesize via a click-chemistry reaction of octavinyl polyhedral oligomeric with alkyl sulfide.The reduce-friction(RF),anti-wear(AW)properties and anti-AO irradiation of POSS-S-R as MACs base oil additives in atmospheric and simulated space environments were systematically investigated for the first time.Results demonstrate that POSS-S-R not only possesses outstanding anti-AO irradiation capacity but also effectively improves the RF and AW of MACs in atmospheric or simulated space surroundings.This improvement is due to the excellent anti-AO irradiation properties of the POSS structure itself and the high load-carrying ability of silicon-containing and sulfur-containing compounds generated by tribo-chemical reactions,which effectively separates the direct contact of the friction interface.We believe that this synthesized POSS-S-R is a promising additive for space lubricants.

关键词： POSS additive reduce-friction anti-wear multialkylated cyclopentanes(MACs) resistant atomic irradiation

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Acute kidney injury following adult lung transplantation

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Chinese Medical Journal 2022年第2期135卷 172-180页

作者： Lei Jing Wenhui Chen Li Zhao Lijuan Guo chaoyang liang Jingyu Chen Chen Wang Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730China Department of Lung Transplantation Centre of Lung TransplantationCentre of Respiratory DiseasesChina-Japan Friendship HospitalBeijing 100029China National Center for Respiratory Medicine Beijing 100029China Institute of Respiratory Medicine Chinese Academy of Medical SciencesBeijing 100029China National Clinical Research Center for Respiratory Diseases Beijing 100029China Wuxi Lung Transplant Center Wuxi People's Hospital affiliated to Nanjing Medical UniversityWuxiJiangsu 214023China

Background:Acute kidney injury(AKI)is a common and serious complication following lung transplantation(LTx),and it is associated with high mortality and morbidity.This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.Methods:This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019.The outcomes were AKI incidence,risk factors,mortality,and kidney recovery.Multivariate analysis was performed to identify independent risk factors.Survival analysis was presented using the Kaplan-Meier curves.Results:AKI occurred in 137 of the 191 patients(71.7%),with transient AKI in 43(22.5%)and persistent AKI in 94(49.2%).AKI stage 1 occurred in 27/191(14.1%),stage 2 in 46/191(24.1%),and stage 3 in 64/191(33.5%)of the AKI patients.Renal replacement therapy(RRT)was administered to 35/191(18.3%)of the patients.Male sex,older age,mechanical ventilation(MV),severe hypotension,septic shock,multiple organ dysfunction(MODS),prolonged extracorporeal membrane oxygenation(ECMO),reintubation,and nephrotoxic agents were associated with AKI(P<0.050).Persistent AKI was independently associated with pre-operative pulmonary hypertension,severe hypotension,post-operative MODS,and nephrotoxic agents.Severe hypotension,septic shock,MODS,reintubation,prolonged MV,and ECMO during or after LTx were related to severe AKI(stage 3)(P<0.050).Patients with persistent and severe AKI had a significantly longer duration of MV,longer duration in the intensive care unit(ICU),worse downstream kidney function,and reduced survival(P<0.050).Conclusions:AKI is common after LTx,but the pathogenic mechanism of AKI is complicated,and prerenal causes are important.Persistent and severe AKI were associated with poor short-and long-term kidney function and reduced survival in LTx patients.

关键词： Acute kidney injury Adult lung transplantation Incidence Outcomes Risk factors

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Clinical Study on the Treatment of Low Anal Fistula in Infants and Young Children by Anal Gland Excision and Virtual Hanging Procedure

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Journal of Clinical and Nursing Research 2024年第3期8卷 18-25页

作者： Hongbo Su Linmei Sun Yimiao liang Jiansheng Hu Yongli Zhang Ni Wei chaoyang Li Lin Tang Department of Anorectology Xi’an Hospital of Traditional Chinese MedicineXi’anChina

Objective:To compare the efficacy of anal adenectomy with virtual hanging wire and anal fistulotomy in the treatment of low anal fistula in infants and children.Methods:60 children with low anal fistula who were admitted to our hospital from October 2021 to March 2022 and met the inclusion criteria were randomly divided into two groups of 30 cases each;the treatment group was treated with anal adenectomy and virtual hanging wire surgery,and the control group was treated with anal fistula resection.The clinical efficacy after treatment was compared.Results:The total effective rate of both groups was 96.67%and the difference between the two groups was not statistically significant(P>0.05).The postoperative pain score of the treatment group was lower than that of the control group(P<0.05).The length of hospitalization and healing time of the treatment group was lower than that of the control group(P<0.05).The anal function of the patients in both groups was normal,and there was no adverse reaction.Conclusion:Anal gland excision and virtual hanging surgery for the treatment of low anal fistula in infants and children have the advantages of mild pain,reduced length of hospitalization,short healing time,and better patient experience as compared to anal fistula excision.

关键词： Anal fistula Anal gland excision Virtual hanging procedure Surgical method Observation index Clinical efficacy

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Emergency physicians’ occupational risks in China

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World Journal of Emergency Medicine 2024年第3期15卷 232-234页

作者： Huaying Jiang Jia Chang Rong Huang Xiayi liang Manning Song Hejing Yuan Shuo Wang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100105China Operation Room Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China School of Marxism Beijing University of Chinese MedicineBeijing 100105China Department of Infectious Diseases(Fever Clinic) Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China

With the rapid development of emergency medicine,emergency physicians are working around the clock,[1]including additional workloads due to sudden public health emergencies and disasters.Occupational risks for emergency physicians are significantly high due to an increasing number of patients with acute and severe diseases,an increased workload.

关键词： physician acute occupational

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IB期肺腺癌患者辅助治疗方案的筛选

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南方医科大学学报 2024年第5期44卷 989-997页

作者：申磊磊陈莹云天洋郭俊唐柳曦张涛梁朝阳刘阳中国人民解放军总医院海南医院胸外科海南三亚572000 中国人民解放军总医院第一医学中心胸外科北京100853

目的探索IB期肺腺癌患者的辅助治疗方案。方法收集2013年1月~2021年12月在我院行手术治疗的IB期肺腺癌患者,根据术后不同辅助治疗模式分为辅助靶向治疗组(EGFR-TKIs)、辅助化疗组(CT)和临床观察组(CO)。对比3组患者的临床资料和随访结果... 详细信息

目的探索IB期肺腺癌患者的辅助治疗方案。方法收集2013年1月~2021年12月在我院行手术治疗的IB期肺腺癌患者,根据术后不同辅助治疗模式分为辅助靶向治疗组(EGFR-TKIs)、辅助化疗组(CT)和临床观察组(CO)。对比3组患者的临床资料和随访结果,无疾病生存期、总生存的分析采用Kaplan-Meier法并行log-rank检验,COX回归分析患者无疾病生存期(DFS)的预测因素。主要研究终点是5年DFS率,次要研究终点为DFS、3年总生存期(OS)以及辅助治疗的安全性。结果共纳入653例术后诊断为IB期肺腺癌患者,其中EGFR-TKIs组111例,CT组108例,CO组434例。中位随访时间43个月,TKIs组、CT组和CO组的5年DFS率分别为92.8%、80.7%及81.7%,TKIs组的5年DFS率显著高于CO组(P<0.01)。TKIs组、CT组和CO组的3年OS均无统计学差异。亚组分析显示,T3~4 cmN0M0中TKIs组、CT组和CO组的5年DFS率分别为92.6%、84.0%及81.4%,TKIs组的5年DFS率显著高于CO组(P<0.05),3组间的3年OS无统计学差异。而T2ViscPlN0M0中TKIs组、CT组和CO组的5年DFS率分别为95.1%、71.4%及83.5%,组间差异并无统计学意义,3组间的3年OS亦无统计学差异。多因素COX回归分析结果显示,年龄(P<0.05;HR 0.631,95%CI 0.401-0.993)、实性结节(P<0.01;HR 7.620,95%CI 3.037-19.121)、微乳头/实性成分(P<0.05;HR 1.776,95%CI 1.010-3.122)、脉管癌栓(P<0.05;HR 2.981,95%CI 1.198-7.419)及辅助治疗(P<0.01)是DFS的独立预测因素。安全性方面,皮疹、甲沟炎及腹泻仍然是靶向药物最常见的不良反应。化疗组不良反应主要为血液系统的抑制和胃肠道反应,3级以上不良反应率高于TKIs组(44.4%vs 9.0%)。结论辅助靶向治疗有助于提高T3~4 cmN0M0的IB期肺腺癌患者的DFS,但T2ViscPlN0M0患者并不能从靶向治疗中获益。辅助化疗并不能改善IB期肺腺癌患者的DFS和OS。

关键词： IB期肺腺癌辅助化疗 EGFR突变靶向治疗无疾病生存期

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Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

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Neural Regeneration Research 2024年第5期19卷 1105-1111页

作者： Tao Liu Ziqian Ma liang Liu Yilun Pei Qichao Wu Songjie Xu Yadong Liu Nan Ding Yun Guan Yan Zhang Xueming Chen Department of Orthopedic Surgery Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Orthopedic Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Department of Stomatology Beijing Luhe HospitalCapital Medical UniversityBeijingChina Department of Anesthesiology and Critical Care Medicine School of MedicineJohns Hopkins UniversityBaltimoreMDUSA Department of Neurological Surgery School of MedicineJohns Hopkins UniversityBaltimoreMDUSA

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

关键词： BV2 conditioned medium dental pulp stem cells GSDMD microglia neuroinflammation NLRP3 pyroptosis spinal cord injury

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中国淡水池塘养殖发展的时空格局与前景展望

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淡水渔业 2024年第2期54卷 42-49页

作者：张辉吴湘香陶玲代梨梨彭亮万朝阳李谷中国水产科学研究院长江水产研究所武汉430223 农业农村部淡水生物多样性保护重点实验室武汉430223 华中农业大学水产学院武汉430070

淡水池塘养殖是我国重要的渔业生产方式,解析其时空发展格局对于研判和把握未来的发展趋势十分必要。本研究以历年来中国渔业统计年鉴数据为基础,对近40年以来(1980-2020年,以5年为间隔;另有2021、2022年)全国31个省级行政单元淡水池塘... 详细信息

淡水池塘养殖是我国重要的渔业生产方式,解析其时空发展格局对于研判和把握未来的发展趋势十分必要。本研究以历年来中国渔业统计年鉴数据为基础,对近40年以来(1980-2020年,以5年为间隔;另有2021、2022年)全国31个省级行政单元淡水池塘养殖产量、面积、单产、占渔业总产量的比例进行了统计分析。结果表明:(1)养殖产量总体呈持续增加趋势,但增长率波动式放缓,1980-2020年增长率从181.9%下降至12.0%,2020-2022年均值为2348.3万吨,平均增长率为2.9%;(2)养殖面积亦呈持续增加趋势,但增长率波动式放缓,从53.1%下降至4.8%,2020-2022年均值261.8万hm^(2),平均增长率为0%;(3)单产总体呈波动式增长,但增长率从82.8%逐步下降至13.7%,2020-2022年均值604.7 kg/667 m^(2),平均增长率为2.4%;(4)各省淡水池塘养殖产量占渔业总产量比重的均值呈先上升后逐渐持平的趋势,1995-2022年波动持平变幅在44.6%~49.0%。受水土资源和环境保护刚性约束,当前淡水池塘养殖发展亟需从数量规模型向质量效益型转变,生态-经济合作型渔业综合体将是未来高质量发展的重要途径。

关键词：池塘淡水渔业水产养殖产量面积时空格局

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公立医院非经济性激励的实践探索

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卫生经济研究 2024年第5期41卷 84-86页

作者：刘姝彤梁素花潘渭洪朝阳浙江省人民医院杭州医学院附属人民医院浙江杭州310014

浙江省人民医院秉持人才是第一资源的理念,提出“以员工为核心”的发展基本点,基于职工实际需求和发展需要,探索运用非经济性激励手段,充分发挥医院工会的作用,打造医院“家文化”,不断提升职工幸福感,调动工作积极性,助力医院高质量发展。

关键词：公立医院非经济性激励高质量发展马斯洛需求理论医院文化

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Quantum Secure Undeniable Signature for Blockchain-Enabled Cold-Chain Logistics System

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Computers, Materials & Continua 2023年第5期75卷 3941-3956页

作者： chaoyang Li Hongxue Shen Xiayang Shi Hui liang College of Software Engineering Zhengzhou University of Light IndustryZhengzhou450001China

Data security and user privacy are two main security concerns in the cold-chain logistics system(CCLS).Many security issues exist in traditional CCLS,destroying data security and user privacy.The digital signature can provide data verification and identity authentication based on the mathematical difficulty problem for logistics data sharing in CCLS.This paper first established a blockchain-enabled cold-chain logistics system(BCCLS)based on union blockchain technology,which can provide secure data sharing among different logistics nodes and guarantee logistics data security with the untampered blockchain ledger.Meanwhile,a lattice-based undeniable signature scheme is designed to strengthen the security of logistics data and user privacy against quantum attacks.This scheme is based on the lattice assumption,which can provide anti-quantum security for BCCLS in the future quantum computer age.It also establishes the undeniable mechanism that guarantees that the actual signer cannot deny a valid signature.Then,security proof shows that this undeniable signature scheme is correct and safe,and an efficiency comparison shows that it is more efficient than other schemes in similar literature.The performance evaluations of transaction throughput and latency show that the proposed BCCLS is efficient and practical.This work can improve the security and efficiency of logistics data management and promote the reform and development of the logistics industry.

关键词： Undeniable signature cold-chain logistics system blockchain privacy-preserving

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