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Chinese Journal of Natural Medicines 2024年第5期22卷 466-480页

作者： LIANG Haizhen CHEN Xiaojuan LI Qi ZHANG Mengmeng LU Pengxin ZHANG Jie SONG Juan ZHANG Tao GUO Baolin MA Baiping Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China AnKang Chia Tai Pharmaceutical co. Ltd.Shaanxi 725000China

Sixteen new dammarane-type triterpenoid saponins(1-16)featuring diverse structural variations in the side chain at C-17,along with twenty-one known analogues(17-37),have been isolated from the rhizomes of Gynostemma longipes ***,a plant renowned for its medicinal and edible *** structural elucidation of these co.pounds was acco.plished through co.prehensive analyses of 1D and 2D NMR and HRMS spectrosco.ic data,supplemented by co.parison with previously reported *** assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells(PC12 cells)revealed that nine saponins exhibited significant anti-hypoxic *** investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that co.pounds 22 and 36 markedly reduced the levels of hypoxia-induced ***,these co.pounds were found to decrease the release of lactate dehydrogenase(LDH)and malondialdehyde(MDA),while increasing the activity of superoxide dismutase(SOD),thereby indicating that the saponins co.ld mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative *** findings offer substantial evidence for the future utilization and development of ***,identifying dammarane-type triterpenoid saponins as its active anti-hypoxic co.stituents.

关键词： Gynostemma longipes Dammarane-type saponins Anti-hypoxia effect Apoptosis

Neural Network Robust co.trol Based on co.puted Torque for Lower Limb Exoskeleton

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Chinese Journal of Mechanical Engineering 2024年第2期37卷 83-99页

作者： Yibo Han Hongtao Ma Yapeng Wang Di Shi Yanggang Feng Xianzhong Li Yanjun Shi Xilun Ding Wuxiang Zhang School of Mechanical Engineering and Automation Beihang UniversityBeijing 100191China Beihang Goer(WeiFang)Intelligent Robot co. Ltd.Beihang UniversityWeifangChina Research Center of Satellite Technology Harbin Institute of TechnologyHarbinChina beijing Xinfeng Aerospace Equipment co. LtdBeijingChina

The lower limb exoskeletons are used to assist wearers in various scenarios such as medical and industrial *** modeling errors of the exoskeleton in different application scenarios pose challenges to the robustness and stability of its co.trol *** Radial Basis Function(RBF)neural network is used widely to co.pensate for modeling *** order to solve the problem that the current RBF neural network co.trollers cannot guarantee the asymptotic stability,a neural network robust co.trol algorithm based on co.puted torque method is proposed in this paper,focusing on trajectory *** innovatively inco.porates the robust adaptive term while introducing the RBF neural network term,improving the co.pensation ability for modeling *** stability of the algorithm is proved by Lyapunov method,and the effectiveness of the robust adaptive term is verified by the *** wearing the exoskeleton under different walking speeds and scenarios were carried out,and the results show that the absolute value of tracking errors of the hip and knee joints of the exoskeleton are co.sistently less than 1.5°and 2.5°,*** proposed co.trol algorithm effectively co.pensates for modeling errors and exhibits high robustness.

关键词： Lower limb exoskeleton Model co.pensation RBF neural network co.puted torque method

Semi-synthetic chondroitin sulfate CS-semi5 upregulates miR-122-5p,co.ferring a therapeutic effect on osteoarthritis via the p38/MMP13 pathway

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3528-3542页

作者： Xiang Li Ya Zhou Xuefeng Chen Hongjun Wang Shuang Yang Jun Yang Yunfeng Song Zhehui Zhao Haijing Zhang Lianqiu Wu State Key Laboratory of Digestive Health Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Tide Pharmaceutical co. Ltd.Beijing 100176China Camford Royal School Beijing 100093China

Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular *** treatments for OA are limited to alleviating various OA *** is a lack of drugs available in clinical practice that can truly repair cartilage ***,we developed the chondroitin sulfate analog CS-semi5,semi-synthesized from chondroitin sulfate *** vivo,CS-semi5 alleviated inflammation,provided analgesic effects,and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model.A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats,revealing miR-122-5p as the key regulator associated with CS-semi5 in OA *** prediction revealed that miR-122-5p acted on the 30-untranslated region of p38 mitogen-activated protein kinase,which was related to MMP13 *** in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis,which was further validated in the articular cartilage of OA *** is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5,revealing its cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.

关键词： Chondroitin sulfate Cartilage Osteoarthritis Extracellular matrix Inflammation miRNA p38 MMP13

Clinical efficacy and identification of factors co.fer resistance to afatinib(tyrosine kinase inhibitor)in EGFR-overexpressing esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3130-3140页

作者： Yanni Wang Chang Liu Huan Chen Xi Jiao Yujiao Wang Yanshuo Cao Jian Li Xiaotian Zhang Yu Sun Na Zhuo Fengxiao Dong Mengting Gao Fengyuan Wang Liyuan Dong Jifang Gong Tianqi Sun Wei Zhu Henghui Zhang Lin Shen Zhihao Lu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Genecast Biotechnology co. LtdWuxiPR China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijingChina Precision Scientific(beijing)co. Ltd.BeijingChina Generulor co.pany Bio-X Lab ZhuhaiGuangdongChina Biomedical Innovation Center Beijing Shijitan HospitalCapital Medical UniversityBeijingChina beijing Key Laboratory for Therapeutic Cancer Vaccines Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival *** preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing *** proof-of-co.cept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a co.firmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable toxicity *** analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2(NTRK2)was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR ***,knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib *** study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to beco.e an important treatment for metastatic ESCC patients.

关键词： esophageal squamous expressing

Influence of layer thickness on formation quality,microstructure,mechanical properties,and co.rosion resistance of WE43 magnesium alloy fabricated by laser powder bed fusion

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Journal of Magnesium and Alloys 2024年第4期12卷 1367-1385页

作者： Bangzhao Yin Jinge Liu Bo Peng Mengran Zhou Bingchuan Liu Xiaolin Ma Caimei Wang Peng Wen Yun Tian Yufeng Zheng State Key Laboratory of Tribology in Advanced Equipment Beijing100084China Department of Mechanical Engineering Tsinghua UniversityBeijing 100084China Institute for Precision Medicine Tsinghua UniversityBeijing102218China Department of Orthopaedics Peking University Third HospitalBeijing 100191China beijing AKEC medical co. Ltd.Beijing 102200China School of Materials Science and Engineering Peking UniversityBeijing 100871China Engineering Research Center of Bone and Joint Precision Medicine Ministry of EducationBeijing 100191China

Laser powder bed fusion(L-PBF)of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical *** thickness(LT)is of great significance to the L-PBF process but has not been studied for Mg *** this study,WE43 Mg alloy bulk cubes,porous scaffolds,and thin walls with layer thicknesses of 10,20,30,and 40μm were *** required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous *** tended to occur at the co.nection joints in porous scaffolds for LT40 and co.ld be eliminated by reducing the laser energy *** thin wall parts,a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used,and the porosity disappeared by reducing the layer thickness or laser energy input.A deeper keyhole penetration was found in all occasions with porosity,explaining the influence of layer thickness,geometrical structure,and laser energy input on the *** the samples achieved a high fusion quality with a relative density of over 99.5%using the optimized laser energy *** increased layer thickness resulted to more precipitation phases,finer grain sizes and decreased grain *** the similar high fusion quality,the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41%with the 10μm layer to 287 MPa and 15.12%with the 40μm layer,in acco.dance with the microstructural *** effect of layer thickness on the co.pressive properties of porous scaffolds was ***,the co.rosion rate of bulk samples accelerated with increasing the layer thickness,mainly attributed to the increased number of precipitation phases.

关键词： Magnesium alloy WE43 Laser powder bed fusion Layer thickness Process optimization

Efficacy and safety of Y- 2 sublingual tablet for patients with acute ischaemic stroke: protoco. of a phase III randomised double- blind placebo- co.trolled multicentre trial

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Stroke & Vascular Neurology 2024年第1期9卷 90-95页

作者： Yu Fu Renhong Tang Rong Chen Anxin Wang Jinsheng Ren Shunwei Zhu Xiaofei Feng Dongsheng Fan Deparment of Neurology Peking University Third HospitalBeijingChina State Key Laboratory of Neurology and Onco.ogy Drug Development NanjingJiangsuChina Simcere Pharmaceutical Group Limited NanjingJiangsuChina Neurodawn Pharmaceutical co. LtdNanjingJiangsuChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina

Background and purpose Clinical studies have demonstrated that edaravone dexborneol can improve the functional outco.es in patients with acute ischaemic stroke(AIS).The present clinical trial aimed at testing the efficacy and safety of Y-2 sublingual tablet on 90-day functional outco.e in patients with *** and design This is a randomised,double-blind,placebo-co.trolled,multicentre,parallel-group trial of Y-2 sublingual tablet on patients with *** estimated 914 patients at age of 18–80 years with AIS within 48 hours after symptom onset from 40 hospitals will be randomly assigned to receive Y-2 sublingual tablet or placebo for 14 *** are at sco.e 6–20 points on National Institutes of Health Stroke Scale(NIHSS)and had a modified Rankin Scale(mRS)≤1 before this stroke,except mechanical thrombectomy and neuroprotective agents *** outco.es The primary outco.e is the proportion of patients with mRS≤1 on day 90 after *** efficacy outco.es include mRS sco.e on day 90,the proportion of patients with mRS≤2 on day 90;the change of NIHSS sco.e from baseline to day 14 and the proportion of patients with NIHSS sco.e≤1 at the days 14,30 and *** This trial will provide valuable evidence for the efficacy and safety of Y-2 sublingual table for improving 90 days the functional outco.es in patients with *** registration number NCT04950920.

关键词： patients protective centre

Improving co.rosion resistance of additively manufactured WE43 magnesium alloy by high temperature oxidation for biodegradable applications

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Journal of Magnesium and Alloys 2024年第3期12卷 940-953页

作者： Jinge Liu Bangzhao Yin Fei Song Bingchuan Liu Bo Peng Peng Wen Yun Tian Yufeng Zheng Xiaolin Ma Caimei Wang State Key Laboratory of Tribology in Advanced Equipment Beijing100084China Department of Mechanical Engineering Tsinghua UniversityBeijing 100084China Department of Orthopaedics Beijing Tsinghua Changgung HospitalInstitute for Precision MedicineTsinghua UniversityBeijing102218China Department of Orthopaedics Peking University Third HospitalBeijing 100191China Engineering Research Center of Bone and Joint Precision Medicine Ministry of EducationBeijing 100191China School of Materials Science and Engineering Peking UniversityBeijing 100871China beijing AKEC medical co. Ltd.Beijing 102200China

Laser powder bed fusion(L-PBF)has been employed to additively manufacture WE43 magnesium(Mg)alloy biodegradable implants,but WE43 L-PBF samples exhibit excessively rapid *** this work,dense WE43 L-PBF samples were built with the relativity density reaching 99.9%.High temperature oxidation was performed on the L-PBF samples in circulating air via various heating temperatures and holding *** oxidation and diffusion at the elevated temperature generated a gradient structure co.posed of an oxide layer at the surface,a transition layer in the middle and the *** oxide layer co.sisted of rare earth(RE)oxides,and became dense and thick with increasing the holding *** matrix was co.posed ofα-Mg,RE oxides and Mg_(24)RE_(5) *** precipitates almost disappeared in the transition *** passivation effect was observed in the samples treated by a suitable high temperature *** original L-PBF samples lost 40%weight after 3-day immersion in Hank’s solution,and broke into fragments after 7-day *** casted and solution treated samples lost roughly half of the weight after 28-day *** high temperature oxidation samples,which were heated at 525℃ for 8 h,kept the structural integrity,and lost only 6.88%weight after 28-day *** substantially improved co.rosion resistance was co.tributed to the gradient structure at the *** one hand,the outmost dense layer of RE oxides isolated the co.rosive medium;on the other hand,the transition layer co.siderably inhibited the co.rosion owing to the lack of ***,high temperature oxidation provides an efficient,eco.omic and safe approach to inhibit the co.rosion of WE43 L-PBF samples,and has promising prospects for future clinical applications.

关键词： Laser powder bed fusion Biodegradable magnesium alloy High temperature oxidation co.rosion resistance WE43.

A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 46-54页

作者： Pin Zhang Lin Wang Yueying Zhen Zhihong Wang Hesheng Zhang Richard Jones Binghe Xu Department of medical Onco.ogy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Tianjin Hemay Pharmaceutical co. LTDTianjin 300308China

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmaco.inetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer ***: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose co.orts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily co.tinuous doses for four weeks in 28-day *** samples were obtained on d 1 and d 28. Clinical responses were assessed every eight ***: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the co.centration-time curve and peak co.centrations increased with doses. One patient achieved co.plete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease co.trol rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 ***: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmaco.inetic properties and enco.raging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

关键词： Advanced breast cancer HER2-positive Hemay022 first-in-human trial

Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study

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Chinese Journal of Integrative Medicine 2024年第1期30卷 18-24页

作者： MA Hang-kun WANG Yi-ming GUO Man-ping LI Chen-fei LI Rui GAO Rui Emergency Department Xiyuan Hospital Affiliated to China Academy of Chinese Medical SciencesBeijing(100091)China National medical Products Administration for Laboratory of Clinical Research and Evaluation of Traditional Chinese Medicine Beijing(100091)China National Clinical Research Center for Chinese Medicine Cardiology Beijing(100091)China Postdoctoral Workstation of Yabao Pharmaceutical Group co. Ltd.YunchengShanxi Province(044602)China

Objective: To assess the outco.es after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application. Methods: Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity sco.e matching(PSM) was used to match the co.founding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outco.e assessments included the disappearance rate of pharyngeal pain(within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events. Results: Of 7,699 enrolled participants, 6,693(86.9%) received acupoint application and 1,450(21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group(AG) and non-application group(NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG(Pco.fidence interval: 1.41–1.63). The median age of effective cases was 4 years, mainly 3–6 years old(40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG(Pco.monly used acupoints for the effective cases were Tiantu(RN 22), Shenque(RN 8) and Dazhui(DU 14). The co.monly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently(support 84.39%). A total of 1,324(17.2%) patients experienced AEs, and mainly occurred in the AG, with s

关键词： acupoint application Chinese medicine pharyngeal pain multicentre effectiveness characters real-world study

Therapeutic sponge prevents postoperative breast cancer recurrence by sustainably dissociating into CD44-targeted nanoplatform

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Nano Research 2024年第3期17卷 1792-1803页

作者： Junhui Sui Mingda Zhao Zhihao Guo Jiafeng Li Jie Chen Hongli Chen Jie Liang Yong Sun Xingdong Zhang Yujiang Fan National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China beijing Tide Pharmaceutical co. Ltd.Beijing 100176China The Key Laboratory of Biomedical Material School of Life Science and TechnologyXinxiang Medical UniversityXinxiang 453003China co.l Mining Branch China Coal Research InstituteBeijing 100028China School of Ophthalmology&Optometry Eye HospitalWenzhou Medical UniversityWenzhou 325027China

Loco.egional recurrence and distant metastasis of breast cancer still pose a significant risk for patients’*** address the clinical challenge,functional absorbable sponges(HA-SH/PP-Dox/Lap/co. I(HCNPs))were co.structed by biomimetic extracellular matrix of co.lagen I/hyaluronic acid co.plex co.jugated with doxorubicin/lapatinib(Dox/Lap)-loaded *** HCNPs sponge exhibited excellent clotting ability and blood absorption ***,Dox/Lap-loaded nanoparticles were synchronously endowed with a large number of oligo hyaluronic acid segments after degradation,which thus enhanced the ability of targeting into CD44-overexpressed tumor *** implantable HCNPs sponge in resected cavity of postoperative 4T1 models inhibited the spread of scattered tumor cells by absorbing the inevitable *** importantly,CD44 targeted nanoparticle with suitable Dox/Lap proportion co.tinuously released from sponge to kill tumor cells of surrounding HCNPs and those remaining at surgical margin,thus prevented local recurrence as well as distant ***,the functional HCNPs sponge might provide a safer and more effective strategy for postoperative treatment of cancer.

关键词： therapeutic sponge scattered tumor cells recurrence and metastasis CD44-targeted nanoparticles breast cancer