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Efficacy of Chinese Medicine Treatment Based on Syndrome Differentiation for Primary Insomnia:A Randomized Placebo Controlled Triple-Blinded Trial

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Chinese Journal of Integrative Medicine 2024年第10期30卷 867-876页

作者： XIONG Zhi-yi LU Ying HE Li-yun ZHANG Run-shun ZHOU Xue-zhong LI Peng LIU Yan-jiao ZHU Jian-gui YAN Shi-yan LIU Bao-yan International Acupuncture and Moxibustion Innovation institute School of Acupuncture-Moxibustion and Tuina Beijing University of Chinese Medicine Department of biomedical Data Science Stanford University School of Medicine institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing Jiaotong University School of Computer and Information Technology Beijing Xicheng District Community Healthcare Center China Academy of Chinese Medical sciences

Objective: To assess efficacy of Chinese medicine(CM) on insomnia considering characteristics of treatment based on syndrome differentiation. Methods: A total of 116 participants aged 18 to 65 years with moderate and severe primary insomnia were randomized to the placebo(n=20) or the CM group(n=96) for a 4-week treatment and a 4-week follow-up. Three CM clinicians independently prescribed treatments for each patient based on syndromes differentiation. The primary outcome was change in total sleep time(TST) from baseline. Secondary endpoints included sleep onset latency(SOL), wake time after sleep onset(WASO), sleep efficiency, Pittsburgh Sleep Quality Index(PSQI) and CM symptoms. Results: The CM group had an average 0.6 h more(95% confidence interval(CI): 0.3–0.9, P<0.001) TST and 34.1%(10.3%–58.0%, P=0.005) more patients beyond 0.5 h TST increment than that of the placebo group. PSQI was changed –3.3(–3.8 to –2.7) in the CM group, a –2.0(–3.2 to –0.8, P<0.001) difference from the placebo group. The CM symptom score in the CM group decreased –2.0(–3.3 to –0.7, P=0.003) more than the placebo group. SOL and WASO changes were not significantly different between groups. The analysis of prescriptions by these clinicians revealed blood deficiency and Liver stagnation as the most common syndromes. Prescriptions for these clinicians displayed relative stability, while the herbs varied. All adverse events were mild and were not related to study treatment. Conclusions: CM treatment based on syndrome differentiation can increase TST and improve sleep quality of primary insomnia. It is effective and safe for primary insomnia. In future studies, the long-term efficacy validation and the exploratory of eutherapeutic clinicians' fixed herb formulas should be addressed.(Registration No. NCT01613183)

关键词： Chinese medicine primary insomnia randomized controlled trial syndrome differentiation

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Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer’s Disease Mouse Model

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Research 2024年第1期2023卷 81-95页

作者： Fangxuan Chu Ruxin Tan Xin Wang Xiaoqing Zhou Ren Ma Xiaoxu Ma Ying Li Ruixu Liu Chunlan Zhang Xu Liu Tao Yin Zhipeng Liu institute of biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China Tianjin institutes of Health Science Tianjin301600China Neuroscience Center Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing100730China

The neuropathological features of Alzheimer’s disease include amyloid *** emerging evidence suggests that Piezo1,a mechanosensitive cation channel,plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure,but the importance of Piezo1-mediated mechanotransduction in brain functions is less ***,apart from mechanical stimulation,Piezo1 channels are strongly modulated by *** assume that Piezo1 may play a role in converting mechanical and electrical signals,which could induce the phagocytosis and degradation of Aβ,and the combined effect of mechanical and electrical stimulation is superior to single mechanical ***,we design a transcranial magneto-acoustic stimulation(TMAS)system,based on transcranial ultrasound stimulation(TUS)within a magnetic field that combines a magnetoacoustic coupling effect electric field and the mechanical force of ultrasound,and applied it to test the above hypothesis in 5xFAD *** tests,in vivo electrophysiological recordings,Golgi–Cox staining,enzyme-linked immunosorbent assay,immunofluorescence,immunohistochemistry,real-time quantitative PCR,Western blotting,RNA sequencing,and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1.

关键词： stimulation Alzheimer Piezo1

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Endovascular embolization by a magnetic microfiberbot

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National Science Review 2024年第5期11卷 95-96页

作者： Shuning Zhang Wenlong Yang Junbo Ge Department of Cardiology Zhongshan HospitalFudan University Shanghai Institute of Cardiovascular Diseases Key Laboratory of Viral Heart Diseases National Health Commission Key Laboratory of Viral Heart Diseases Chinese Academy of Medical Sciences National Clinical Research Center for Interventional Medicine institutes of biomedical sciences Fudan University

The evolving landscape of embolization therapy for treating cerebral aneurysms and brain tumors represents a pivotal stride towards enhancing the efficacy and safety of minimally invasive treatments [1]. Conventional endovascular embolization methods [2], characterized by the manual maneuvering of catheters through the vascular system, present notable limitations in steerability and precision, compounded by the potential health risks associated with prolonged exposure to radiation for surgeons.

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D-type neuropeptide decorated AIEgen/RENP hybrid nanoprobes with light-driven ROS generation ability for NIR-Ⅱ fluorescence imaging-guided through-skull photodynamic therapy of gliomas

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Aggregate 2024年第1期5卷 185-195页

作者： Xuelu He Yuan Luo Yanying Li Yuanbo Pan Ryan T.K.Kwok Lulu He Xiaolin Duan Pengfei Zhang Aiguo Wu Ben Zhong Tang Juan Li Ningbo Key Laboratory of biomedical Imaging Probe Materials and Technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingboP.R.China Guangdong Key Laboratory of Nanomedicine Shenzhen Engineering Laboratory of Nanomedicine and NanoformulationsCAS-HK Joint Lab for BiomaterialsResearch Laboratory for Biomedical Optics and Molecular ImagingShenzhen Key Laboratory for Molecular ImagingCAS Key Lab for Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenP.R.China Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced StudyThe Hong Kong University of Science and Technology(HKUST)KowloonP.R.China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhenP.R.China

Glioma is one of the most common malignant tumors of the central nervous system,leading high mortality rates in ***-induced emission(AIE)photosensitizers-based photodynamic therapy(PDT)has emerged as a promising therapeutic strategy for least-invasive treatment of glioma,which involves local irradiation of the tumor using an external near-infrared(NIR)***,most AIE photosensitizers suffered from poorly penetration of the visible light excitation,bad spatiotemporal resolution in deep tissues and low efficient blood-brain barrier(BBB)crossing ability,which greatly limited the clinical practice of AIE photosensitizers for especially deep-seated brain tumor *** this work,we developed a multifunctional NIR-driven theranostic agent through hybrid of AIE photosensitizers TIND with rare-earth doping nanoparticles(RENPs)NaGdF4:Nd/Yb/Tm with up/down dual-mode conversion *** theranostic agent was further decorated with D-type neuropeptide DNPY for crossing BBB and targeting *** the 808-nm light irradiation,the down-conversion NIR-II luminescence could indicate the position glioma and the upconversion NIR-I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in *** results demonstrate that the integration of Dtype neuropeptide,AIE photosensitizers and RENPs could be promising candidates for in vivo NIR-II fluorescence image-guided through-skull PDT treatments of brain tumors.

关键词： aggregation-induced emission D-type neuropeptide glioma photodynamic therapy rare-earth doping nanoparticles

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A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys

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Neuroscience Bulletin 2024年第1期40卷 90-102页

作者： Yefei Chen Jingyi Wang Jing Liu Jianbang Lin Yunping Lin Jinyao Nie Qi Yue Chunshan Deng Xiaofei Qi Yuantao Li Ji Dai Zhonghua Lu Department of Anesthesiology Shenzhen Maternity and Child Healthcare HospitalThe First School of Clinical MedicineSouthern Medical UniversityShenzhen 518027China Shenzhen Technological Research Center for Primate Translational Medicine Shenzhen Key Laboratory for Molecular Biology of Neural DevelopmentShenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of sciences Beijing 100049China CAS Key Laboratory of Brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Guangdong Provincial Key Laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China biomedical Research institute Hubei University of MedicineShiyan 442000China Faculty of Life and Health sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Retrograde adeno-associated viruses(AAVs)are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural ***,few retro-grade AAV capsids have been shown to offer access to cor-tical projection neurons across different species and enable the manipulation of neural function in non-human primates(NHPs).Here,we report the development of a novel retro-grade AAV capsid,AAV-DJ8R,which efficiently labeled cortical projection neurons after local administration into the striatum of mice and *** addition,intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral ***,AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque *** data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

关键词： Retrograde AAV Capsid variant Cortical projection neuron Optogenetics Monkey

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Imaging of human parafoveal area with large field of view in adaptive optics line scanning ophthalmoscope

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Journal of Innovative Optical Health sciences 2024年第6期17卷 41-51页

作者： Wen Kong Yiwei Chen Guohua Shi Yi He Department of biomedical Engineering University of Science and Technology of ChinaHefei 230041P.R.China Jiangsu Key Laboratory of Medical Optics Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhou 215163P.R.China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031P.R.China Key Laboratory of Myopia of State Health Ministry and Key Laboratory of Visual Impairment and Restoration of ShanghaiShanghai 200003P.R.China

The parafoveal area,with its high concentration of photoreceptors andfine retinal capillaries,is crucial for central vision and often exhibits early signs of pathological *** current adaptive optics scanning laser ophthalmoscope(AOSLO)provides an excellent tool to acquire accurate and detailed information about the parafoveal area with cellular ***,limited by the scanning speed of two-dimensional scanning,thefield of view(FOV)in the AOSLO system was usually less than or equal to 2,and the stitching for the parafoveal area required dozens of images,which was time-consuming and ***,almost half of patients are unable to obtain stitched images because of their *** solve this problem,we integrate AO technology with the line-scan imaging method to build an adaptive optics line scanning ophthalmoscope(AOLSO)system with a larger *** the AOLSO,afocal spherical mirrors in pairs are nonplanar arranged and the distance and angle between optical elements are optimized to minimize the aberrations,two cylinder lenses are orthogonally placed before the imaging sensor to stretch the point spread function(PSF)for su±ciently digitizing light *** human retinal images show the whole parafoveal area with 55FOV,60 Hz frame rate and cellular *** advantage of the 5FOV of the AOLSO,only 9 frames of the retina are captured with several minutes to stitch a montage image with an FOV of 99,in which photoreceptor counting is performed within approximately 5*** AOLSO system not only provides cellular resolution but also has the capability to capture the parafoveal region in a single frame,which offers great potential for noninvasive studying of the parafoveal area.

关键词： Adaptive optics line scanning retinal imaging system parafoveal capillary vasculature.

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Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

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Asian Journal of Pharmaceutical sciences 2024年第1期19卷 69-85页

作者： Noehyun Myung Hyun-Wook Kang Department of biomedical Engineering Ulsan National Institute of Science and Technology(UNIST)Ulju-gun 44919South Korea

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor *** treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive ***,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical ***,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release *** implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose *** device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a *** density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in *** the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral *** demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC *** density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance *** the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

关键词： Dose-dense chemotherapy Triple-negative breast cancer 3D printing Pulsatile release Local drug delivery systems

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Neurogenic potential of NG2 in neurotrauma:a systematic review

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Neural Regeneration Research 2024年第12期19卷 2673-2683页

作者： Yuri R.Rigo Radharani Benvenutti Luis V.Portela Nathan R.Strogulski Departamento de Bioquímica Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do Sul(UFRGS)Porto AlegreBrazil School of Pharmacy and Biomolecular sciences RCSI University of Medicine and Health SciencesDublinIreland School of Biochemistry and Immunology Trinity Biomedical Sciences InstituteTrinity College DublinUniversity of DublinDublinIreland

Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of *** is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic to rgets in spinal co rd and traumatic brain *** advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma *** studies using neural-glial factor/antigen 2(NG2)cells indicate that they may differentiate into neurons even in the developed *** these cells show great potential to play a regenerative role,studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from *** the present study,we systematically reviewed the experimental protocols and findings described in the scientific literature,which were peer-reviewed original research articles(1)describing preclinical experimental studies,(2)investigating NG2 cells,(3)associated with neurogenesis and neurotrauma,and(4)in vitro and/or in vivo,available in PubMed/MEDLINE,Web of Science or SCOPUS,from 1998 to ***,we have reviewed a total of 1504 papers,and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in *** also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal co rd injury models,and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury *** findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.

关键词： neural-glial antigen 2 neural-glial factor 2 neuron differentiation NG2 cell regeneration spinal cord injury(SCI) traumatic brain injury(TBI)

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Tumor microenvironment-responsive arsenic-loaded layered double hydroxides film with synergistic anticancer and bactericidal activity

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Rare Metals 2024年第3期43卷 1207-1221页

作者： Shun Xing Dong-Hui Wang Hai-Feng Zhang Li-Dan Liu Cheng-Ce Li Chao Wei Jun-Yu Liu Nai-Jian Ge Xuan-Yong Liu State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing100049China Intervention Center Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai200438China School of Health sciences and biomedical Engineering Hebei University of TechnologyTianjin300130China

Malignant obstruction makes gallbladder cancer have a high mortality ***-titanium alloy(nitinol)stents are commonly used as a local intervention to maximize patient survival time,but the stents lack antitumor and antibacterial capacity and are vulnerable to secondary ***-based drugs show good therapeutic promise against gallbladder *** meet clinical *** layered double hydroxides(LDHs)film is constructed on the nitinol,whose arsenite loading amounts rose by 60%after simple heat treatment compared with the conventional anion-exchange *** addition,calcination promotes the dissolution of nickel ions from the LDHs lattice,resulting in a powerful synergistic killing effect on tumor cells together with the released *** importantly,the calcined arsenic-loaded LDHs are sensitive to the acidic microenvironment of tumor tissues,which presents a much lower arsenic and nickel release amount in the normal tissues,guaranteeing its ***,the vertically sharp LDHs nanosheets can synergize with arsenic to achieve effective physical cleavage and chemical killing of adherent and planktonic *** short,we attempt to use arsenic drugs for local interventions and reasonably avoid their toxic side effects,which provides a new design idea for nitinol stents applied in the treatment of gallbladder cancer.

关键词： Nitinol Layered double hydroxides Arsenic Gallbladder cancer

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N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA

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National Science Review 2024年第3期11卷 72-91页

作者： Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat-sen University Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine Department of biomedical sciences City University of Hong Kong institute of Systems and Physical Biology Shenzhen Bay Laboratory

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer（CRC） cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione（GSH） via the upregulation of RRM2B——a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3 UTR of RRM2B increased its m RNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence（CDS） of OPA1——an essential GTPase protein for mitochondrial inner membrane fusion——also increased m RNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

关键词： m6A mitochondrial fusion glutathione OPA1 colorectal cancer

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