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Gabapentinoids for the treatment of stroke

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Neural Regeneration Research 2024年第7期19卷 1509-1516页

作者： Ying Zhang Chenyu Zhang Xiaoli Yi Qi Wang Tiejun Zhang Yuwen Li Department of Pharmacy West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Neurosurgery West China HospitalSichuan UniversityChengduSichuan ProvinceChina

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.

关键词： cortical spreading depolarization gabapentinoid intracerebral hemorrhage pain after stroke stroke subarachnoid hemorrhage

Engineering high-performance dielectric chiral shells with enhanced chiral fields for sensitive chiral biosensor

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Rare Metals 2024年第3期43卷 1197-1206页

作者： Yi-Fan Wang Shan-Shan Huang Zhen-Dong Dai Shi-Lin Xian Xuan-Nan Wu Fu-Hua Gao Yi-Dong Hou College of Physics Sichuan UniversityChengdu610065China Graduate School of sichuan university Sichuan UniversityChengdu610065China

Chiral metamaterials have been a topic of significant research interest in recent years due to their potential for various applications in nanophotonic devices and chiral biosensors.However,the intrinsic Ohmic loss in surface plasmonic resonance has limited their practical use,resulting in large light dissipation and weak chiroptical resonance.Here,we report on the development of high-performance dielectric chiral shells(DCS)through a two-step Si deposition process on a self-assembled microsphere monolayer.The form DCS sample completely oyercomes the cancelation effect originated from the disorder property of the micro-sphere monolayer in macroscale,and at a wavelength of approximately 710 nm,the measured optimal chiral signal(g-factor)and transmittance can reach up to 0.7 and 0.3,respectively.The strong chiroptical effect comes from the asymmetric circular displacement currents(i.e.,magnetic modes)enabled by the specific shell geometry.The chiral shell geometry,electromagnetic properties,sensor sensitivity of chiral molecules and figure of merit are systematically investigated.The DCSs demonstrate highly sensitive detection of chiral biomolecules owing to their easily accessible geometry and enhanced uniform chiral field.

关键词： Dielectric chiral shells(DCS) Si deposition Magnetic resonance Highly sensitive sensor Chiral field

Association of interpregnancy interval and risk of adverse pregnancy outcomes in woman by different previous gestational ages

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Chinese Medical Journal 2024年第1期137卷 87-96页

作者： Peiran Chen Yi Mu Zheng Liu Yanping Wang Xiaohong Li Li Dai Qi Li Mingrong Li Yanxia Xie Juan Liang Jun Zhu National Office for Maternal and Child Health Surveillance of China West China Second University HospitalSichuan UniversityChengduSichuan 610066China Department of Obstetrics West China Second University HospitalSichuan UniversityChengduSichuan 610066China Key Laboratory of Birth Defects and Related Diseases of Women and Children Ministry of EducationSichuan UniversityChengduSichuan 610066China

Background:With an increasing proportion of multiparas,proper interpregnancy intervals(IPIs)are urgently needed.However,the association between IPIs and adverse perinatal outcomes has always been debated.This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods:We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019.Multivariable Poisson models with restricted cubic splines were used.Each adverse outcome was analyzed separately in the overall model and stratified models.The stratified models included different categories of fertility policy periods(2014-2015,2016-2017,and 2018-2019)and infant gestational age in previous pregnancy(<28 weeks,28-36 weeks,and≥37 weeks).Results:There were 781,731 pregnancies enrolled in this study.A short IPI(≤6 months)was associated with an increased risk of preterm birth(OR[95%CI]:1.63[1.55,1.71]for vaginal delivery[VD]and 1.10[1.03,1.19]for cesarean section[CS]),low Apgar scores and small for gestational age(SGA),and a decreased risk of diabetes mellitus in pregnancy,preeclampsia or eclampsia,and gestational hypertension.A long IPI(≥60 months)was associated with an increased risk of preterm birth(OR[95%CI]:1.18[1.11,1.26]for VD and 1.39[1.32,1.47]for CS),placenta previa,postpartum hemorrhage,diabetes mellitus in pregnancy,preeclampsia or eclampsia,and gestational hypertension.Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes.The estimated risk of preterm birth,low Apgar scores,SGA,diabetes mellitus in pregnancy,and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion:For pregnant women with shorter or longer IPIs,more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

关键词： Interpregnancy interval Fertility policy Gestational age Preterm birth Gestational hypertension Diabetes mellitus in pregnancy

Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

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Neural Regeneration Research 2024年第10期19卷 2157-2174页

作者： Shihong Zhu Xiaoyin Liu Xiyue Lu Qiang Liao Huiyang Luo Yuan Tian Xu Cheng Yaxin Jiang Guangdi Liu Jing Chen Department of Neurosurgery West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Pharmacy West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Out-patient Department West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Respiratory and Critical Care Medicine West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the

关键词： bioactive materials biomaterials exosomes neural regeneration scaffolds stem cells tissue engineering traumatic brain injury

NCAD v1.0: a database for non-coding variant annotation and interpretation

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Journal of Genetics and Genomics 2024年第2期51卷 230-242页

作者： Xiaoshu Feng Sihan Liu Ke Li Fengxiao Bu Huijun Yuan Institute of Rare Diseases West China HospitalSichuan UniversityChengduSichuan 610044China

The application of whole genome sequencing is expanding in clinical diagnostics across various genetic disorders, and the significance of non-coding variants in penetrant diseases is increasingly being demonstrated. Therefore, it is urgent to improve the diagnostic yield by exploring the pathogenic mechanisms of variants in non-coding regions. However, the interpretation of non-coding variants remains a significant challenge, due to the complex functional regulatory mechanisms of non-coding regions and the current limitations of available databases and tools. Hence, we develop the non-coding variant annotation database (NCAD, http://***/), encompassing comprehensive insights into 665,679,194 variants, regulatory elements, and element interaction details. Integrating data from 96 sources, spanning both GRCh37 and GRCh38 versions, NCAD v1.0 provides vital information to support the genetic diagnosis of non-coding variants, including allele frequencies of 12 diverse populations, with a particular focus on the population frequency information for 230,235,698 variants in 20,964 Chinese individuals. Moreover, it offers prediction scores for variant functionality, five categories of regulatory elements, and four types of non-coding RNAs. With its rich data and comprehensive coverage, NCAD serves as a valuable platform, empowering researchers and clinicians with profound insights into non-coding regulatory mechanisms while facilitating the interpretation of non-coding variants.

关键词： Non-coding variants Annotation Variant interpretation Database

Stromal lenticule addition keratoplasty with corneal crosslinking for corneal ectasia secondary to FS-LASIK:a case series

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 596-602页

作者： Li-Xiang Wang Ying-Ping Deng Meng-Zhen Xie Ke Ma Hong-Bo Yin Qiong Wang Rui Gong Jing Tang Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina West China School of Medicine Sichuan UniversityChengdu 610041Sichuan ProvinceChina

●AIM:To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty(SLAK)with corneal crosslinking(CXL)on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis(FS-LASIK).●METHODS:A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo.The lenticules were collected from patients undertaking small incision lenticule extraction(SMILE)for the correction of myopia.Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength.●RESULTS:All surgeries were conducted successfully with no significant complications.Their best corrected visual acuity(BCVA)ranged from 0.05 to 0.8-2 before surgery.The pre-operational total corneal thickness ranged from 345-404μm and maximum keratometry(Kmax)ranged from 50.8 to 86.3.After the combination surgery,both the corneal keratometry(range 55.9 to 92.8)and total corneal thickness(range 413-482μm)significantly increased.Four out of 5 patients had improvement of corneal biomechanical parameters(reflected by stiffness parameter A1 in Corvis ST).However,3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze.Despite the onset of corneal edema right after SLAK,the corneal topography and thickness generally stabilized after 3mo.●CONCLUSION:SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia.Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

关键词： corneal ectasia femtosecond laserassisted in situ keratomileusis stromal lenticule addition keratoplasty corneal crosslinking corneal thickness corneal biomechanics

A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

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Regenerative Biomaterials 2024年第2期3卷 123-136页

作者： Haoshuang Wu Nuoya Chen Tiantian Zheng Li Li Mengyue Hu Yumei Qin Gaoyang Guo Li Yang Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China Institute of Clinical Pathology West China Hospital of Sichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over decades.Most clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed endothelializa-tion.Here,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs.In particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond interactions.Then,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates.In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification properties.Therefore,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

关键词： bioprosthetic heart valves recombinant humanized collagen typeⅢ endothelialization anti-calcification anti-coagulation

Computed tomography radiogenomics:A potential tool for prediction of molecular subtypes in gastric stromal tumor

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1296-1308页

作者： Xiao-Nan Yin Zi-Hao Wang Li Zou Cai-Wei Yang Chao-Yong Shen Bai-Ke Liu Yuan Yin Xi-Jiao Liu Bo Zhang Gastric Cancer Research Center West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Paediatric Surgery West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Radiology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Gastrointestinal Surgery Sichuan University West China HospitalChengdu 610041Sichuan ProvinceChina

BACKGROUND Preoperative knowledge of mutational status of gastrointestinal stromal tumors(GISTs)is essential to guide the individualized precision therapy.AIM To develop a combined model that integrates clinical and contrast-enhanced computed tomography(CE-CT)features to predict gastric GISTs with specific genetic mutations,namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions.METHODS A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio.The models were constructed using selected clinical features,conventional CT features,and radiomics features extracted from abdominal CE-CT images.Three models were developed:ModelCT sign,modelCT sign+rad,and model CTsign+rad+clinic.The diagnostic performance of these models was evaluated using receiver operating characteristic(ROC)curve analysis and the Delong test.RESULTS The ROC analyses revealed that in the training cohort,the area under the curve(AUC)values for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic)for predicting KIT exon 11 mutation were 0.743,0.818,and 0.915,respectively.In the validation cohort,the AUC values for the same models were 0.670,0.781,and 0.811,respectively.For predicting KIT exon 11 codons 557-558 deletions,the AUC values in the training cohort were 0.667,0.842,and 0.720 for model_(CT sign),model_(CT sign+rad),and modelCT_(sign+rad+clinic),respectively.In the validation cohort,the AUC values for the same models were 0.610,0.782,and 0.795,respectively.Based on the decision curve analysis,it was determined that the model_(CT sign+rad+clinic)had clinical significance and utility.CONCLUSION Our findings demonstrate that the combined modelCT_(sign+rad+clinic)effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions.This combined model has the potential to be valuable in assessing the genotype of GISTs.

关键词： Gastrointestinal stromal tumor Radiomics Gene mutation Computed tomography Model

Gut virome:The next frontier in the treatment of necrotizing enterocolitis

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Chinese Medical Journal 2024年第5期137卷 562-564页

作者： Shuqin Zeng Li Zeng Panyu Yang Qu Zheng Shaopu Wang Department of Pediatrics Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationWest China Second University HospitalSichuan UniversityChengduSichuan 610041China sichuan Jinxin Xinan Women&Children Hospital ChengduSichuan 610000China

Necrotizing enterocolitis(NEC)is a devastating gastrointestinal disease over decades,which,however,remains the leading cause of morbidity and mortality in preterm infants.^([1])Although multiple factors,including gastrointestinal tract bacterial colonization,immaturity,and formula feeding,are reported to be involved in the pathogenesis of NEC,the precise mechanisms are not well understood.Owing to the advances in metagenomic sequencing,ample evidences have illustrated the presence of gut dysbacteriosis in infants with NEC,which is characterized by an elevated abundance of Proteobacteria,reduced abundance of Firmicutes phyla,and an overall decrease in bacterial diversity,providing novel insights into NEC progression.^([1,2])Additionally,the bacterial replication rates,particularly those of Enterobacteriaceae,rapidly increase two days prior to NEC diagnosis.^([2])

关键词： elevated frontier treatment