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A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections

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Frontiers of Medicine 2024年第1期18卷 169-179页

作者： xu Hao Zhiyao Bao Ranran Dai Xiaojing Wu Xin Li Muyin Zhang Hao Li lili xu Panpan Qiao xuefei Liu Weiting Hu Ze Zhang Jie Fang Min Zhou Weiming Wang Jieming Qu Department of Nephrology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Department of Pulmonary and Critical Care Medicine Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Institute of Respiratory Diseases Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Pharmacy Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were recruited.Laboratory parameters and chest CT(computed tomography)imaging were analyzed.The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic treatment.No serious adverse reactions or safety events were recorded.Four control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P<0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day 8.Moreover,83.3%of the patients in the treatment group and 57.1%of the patients in the control group turned negative within 22 days.In the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day 1.Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients.The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

关键词： Paxlovid hemodialysis SARS-CoV-2 viral load chest CT scan

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Rapid Prediction of Wastewater Index Using CNN Architecture and PLS Series Statistical Methods

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Open Journal of Statistics 2024年第3期14卷 243-258页

作者： Qiushuang Mo lili xu Fangxiu Meng Shaoyong Hong xuemei Lin School of Mathematics and Statistics Guilin University of Technology Guilin China College of Marine Sciences Beibu Gulf University Qinzhou China School of Data Science Guangzhou Huashang College Guangzhou China Community Management Office Guilin University of Technology Guilin China

Chemical oxygen demand (COD) is an important index to measure the degree of water pollution. In this paper, near-infrared technology is used to obtain 148 wastewater spectra to predict the COD value in wastewater. First, the partial least squares regression (PLS) model was used as the basic model. Monte Carlo cross-validation (MCCV) was used to select 25 samples out of 148 samples that did not conform to conventional statistics. Then, the interval partial least squares (iPLS) regression modeling was carried out on 123 samples, and the spectral bands were divided into 40 subintervals. The optimal subintervals are 20 and 26, and the optimal correlation coefficient of the test set (RT) is 0.58. Further, the waveband is divided into five intervals: 17, 19, 20, 22 and 26. When the number of joint intervals under each interval is three, the optimal RT is 0.71. When the number of joint subintervals is four, the optimal RT is 0.79. Finally, convolutional neural network (CNN) was used for quantitative prediction, and RT was 0.9. The results show that CNN can automatically screen the features inside the data, and the quantitative prediction effect is better than that of iPLS and synergy interval partial least squares model (SiPLS) with joint subinterval three and four, indicating that CNN can be used for quantitative analysis of water pollution degree.

关键词： Wastewater Near-Infrared Spectroscopy Chemistry Oxygen Demand Partial Least Squares Convolutional Neural Network Statistical Optimization

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Wide‑field swept‑source OCT angiography of the periarterial capillary‑free zone before and after anti‑VEGF therapy for branch retinal vein occlusion

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Eye and Vision 2024年第2期10卷 31-40页

作者： Wenyi Tang Wei Liu Jingli Guo lili Zhang Gezhi xu Keyan Wang Qing Chang Department of Ophthalmology Eye and ENT Hospital of Fudan University83 Fenyang RoadShanghai 200031China Shanghai Key Laboratory of Visual Impairment and Restoration Fudan UniversityShanghaiChina NHC Key Laboratory of Myopia(Fudan University) Laboratory of MyopiaChinese Academy of Medical SciencesShanghaiChina

Background:The aim of the study was to investigate the changes in the periarterial capillary-free zone(paCFZ)after anti-vascular endothelial growth factor(VEGF)therapy in patients with branch retinal vein occlusion(BRVO)by widefield swept-source optical coherence tomography angiography(SS-OCTA)and assess their associations with clinical outcomes.Methods:In this retrospective observational study of 54 treatment-naive BRVO patients with macular edema,we reviewed the findings of 12×12 mm^(2)SS-OCTA at baseline,3,6,and 12 months after intravitreal ranibizumab injections.The paCFZ and major retinal artery areas were measured on SS-OCTA images.The paCFZ area to artery area(P/A)ratio was calculated.Results:The paCFZ areas and P/A ratios of first-and second-order arteries were significantly greater in BRVO eyes than in contralateral eyes(all P<0.01),but there were no differences in the first-and second-order artery areas(P=0.20 and 0.25,respectively).The paCFZ areas and P/A ratios decreased significantly at 3,6,and 12 months after anti-VEGF therapy(all P<0.01).The baseline P/A ratio was significantly correlated with the baseline best-corrected visual acuity(BCVA),central retinal thickness,and their improvements at 3,6,and 12 months(all P<0.05).Baseline BCVA and P/A ratios of first-and second-order arteries were independently associated with the final BCVA in multivariate linear regression.Conclusions:Wide-field SS-OCTA shows that anti-VEGF therapy can lead to a significant improvement in the paCFZ parameters in BRVO.Smaller baseline P/A ratios on SS-OCTA tend to predict better visual outcomes at 12 months after anti-VEGF therapy.

关键词： Swept-source optical coherence tomography angiography Branch retinal vein occlusion Periarterial capillary free zone Anti-VEGF treatment Prognosis

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Rapid analysis of metal ions and organic compounds in strong acidic solutions by nano-ESI mass spectrometry

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Chinese Chemical Letters 2024年第2期35卷 516-520页

作者： Jiaquan xu Ting Li Zhendong Yu lili Song Xiu-Xiu xu Hui Li Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation East China University of TechnologyNanchang 330013China Department of Rehabilitation Medicine The First Affiliated Hospital of Nanchang UniversityNanchang 330006China

Rapid analysis of metal ions and organic compounds in strong acidic solutions is of sustainable interest in multiple disciplines.However,complicated and time-consuming pretreatments are always required for MS analysis of the compounds in strong acidic solutions.Otherwise,it will result in a weak signal and cause serious damage to the mass spectrometer.Herein,a simple method inherited from nano-ESI MS was developed for rapid analysis of strong acidic solutions.Nanoliter(nL)strong acidic solution was first loaded in the nano-ESI emitter,followed by evaporation to remove the H+and leave the analytes on the wall of the nano-ESI emitter.The evaporation process can be completed within 1 min because of the extremely tiny volume(≤1 nL)of the loaded solution.Then,the dried analytes on the wall of the nano-ESI emitter were redissolved by loading a new solvent,followed by nano-ESI MS analysis.By using this method,metal ions and organic compounds in the strong acidic solution can be detected with low sample consumption(1 nL),high speed(90%).Proof-of-concept applications of the present method have been successfully achieved for the analysis of gastric juice(pH of the sample=1),monitoring reaction catalyzed by strong acid(pH of the system=0),and micro-area analysis of ores(pH of the extraction solvent=0),showing great application potential in multiple fields.

关键词： Strong acidic solutions Nano-ESI MS Rapid analysis Reaction monitoring Micro-area analysis Gastric juice analysis

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Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia:effects on neurobehavioral phenotypes

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Neural Regeneration Research 2024年第12期19卷 2760-2772页

作者： Xiaowen xu Xinxin Wang Li Zhang Yiming Jin lili Li Meifang Jin Lianyong Li Hong Ni Division of Brain Science Institute of Pediatric ResearchChildren’s Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Pediatric Orthopedics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy.Currently,there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury.Here,we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide,which can protect against hypoxic injury in adulthood,in a mouse model of neonatal hypoxic-ischemic brain injury.In this study,nicotinamide adenine dinucleotide(5 mg/kg)was intraperitoneally administered 30 minutes befo re surgery and every 24 hours thereafter.The results showed that nicotinamide adenine dinucleotide treatment improved body weight,brain structure,adenosine triphosphate levels,oxidative damage,neurobehavioral test outcomes,and seizure threshold in experimental mice.Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice.Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine(or cysteine)peptidase inhibitor,clade A,member 3N,fibronectin 1,5'-nucleotidase,cytosolic IA,microtubule associated protein 2,and complexin 2.Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways(e.g.,nuclear factor-kappa B,mitogen-activated protein kinase,and phosphatidylinositol 3 kinase/protein kinase B).These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

关键词： brain injury cerebral palsy hypoxia hypoxic-ischemic brain injury inflammation neuroprotection nicotinamide adenine dinucleotide neonate nicotinamide adenine dinucleotide proteomics

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Novel CoP/CoMoP_(2) heterojunction with nanoporous structure as an efficient electrocatalyst for hydrogen evolution

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Nano Research 2024年第5期17卷 3693-3699页

作者： lili Zhang Xinxing Shi Aijiao xu Wenwu Zhong Jitang Zhang Shijie Shen Zhejiang Provincial Key Laboratory for Cutting Tools Taizhou UniversityJiaojiang 318000China

The exploration of new heterojunction materials is of great significance in reducing the cost of existing noble metal catalysts and thus realizing the large-scale application of electrocatalytic hydrolysis technology.Herein,a novel CoP/CoMoP_(2) heterojunction was synthesized and served as a hydrogen evolution reaction(HER)electrocatalyst.The heterojunction has morphology of nanoporous structure,which is conducive to exposing more active sites and facilitating bubbles transport.The charge distribution is optimized by a strong interface interaction between CoP and CoMoP_(2).The catalyst’s conductivity and the adsorption properties of the intermediates have both been enhanced.CoP/CoMoP_(2) demonstrates excellent HER activity with an overpotential of 93.6 mV at 10 mA∙cm^(-2),which is competitive with the reported performance of analogous electrocatalysts.This work provides insights into the development of innovative phosphide-based heterojunction electrocatalysts.

关键词： nanoporous CoP CoMoP_(2) heterojunction hydrogen evolution reaction

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Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression,activity,and stability

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Journal of Pharmaceutical Analysis 2024年第1期14卷 69-85页

作者： Chen Hong Yifan Zhang lili Yang Haoyang xu Kang Cheng Zhi Lv Kaixian Chen Yiming Li Huali Wu Department of TCM Chemistry School of PharmacyShanghai University of Traditional Chinese MedicineShanghai200000China Department of Dermatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200000China International Education College Shanghai University of Traditional Chinese MedicineShanghai200000China Shanghai Inoherb Cosmetics Co. Ltd.Shanghai200000China

Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investigation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

关键词： Epimedin B Melanosome Tyrosinase Melanogenesis

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Huoxue Jiedu Huayu recipe(活血解毒化瘀方) inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats

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Journal of Traditional Chinese Medicine 2024年第3期44卷 458-467页

作者： GAO Xiaomeng QIANG Panpan CHANG Jingyue FAN lili YANG Fan xu Qingyou Graduate School Hebei University of Chinese Medicine Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns Hebei University of Chinese Medicine Institute of Integrative Medicine Hebei University of Chinese Medicine

OBJECTIVE: To elucidate the mechanism by which Huoxue Jiedu Huayu recipe( 活血解毒化瘀方, HJHR) regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO) rats and the mechanism by which it reduces of renal fibrosis. METHODS: Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group(180 d of left ureter ligation), UUO plus eplerenone(EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis-and fibrosis-related indexes were detected. RESULTS: HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin(α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A(VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited. CONCLUSIONS: These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFAinduced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.

关键词： aldosterone epithelial-mesenchymal transition eplerenone Huoxue Jiedu Huayu recipe mineralocorticoid receptors unilateral ureteral obstruction

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Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

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Neural Regeneration Research 2025年第5期20卷 1416-1430页

作者： Mou Gao Qin Dong Dan Zou Zhijun Yang lili Guo Ruxiang xu Department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurosurgery Chinese PLA General HospitalBeijingChina Department of Neurology Fu Xing HospitalCapital Medical UniversityBeijingChina

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregu

关键词： Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell microglia neuroinflammation

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GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li Xiang Cao Xinya Gu Mengqi Dong lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang Yun xu Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China Nanjing Neurology Medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels.Immune inflammation is associated with the occurrence and development of MMD.However,the mechanisms underlying the formation of the abnormal vascular network remain unclear.Twenty-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in MMD.We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and chemotaxis.In summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

关键词： Moyamoya disease Vascular endothelial cells GM-CSF VEGF

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