Mitigated reaction kinetics between lithium metal anodes and electrolytes by alloying lithium metal with low-content magnesium

Lithium(Li)metal is regarded as a promising anode candidate for high-energy-density rechargeable batteries.Nevertheless,Li metal is highly reactive against electrolytes,leading to rapid decay of active Li metal reservoir.Here,alloying Li metal with low-content magnesium(Mg)is proposed to mitigate the reaction kinetics between Li metal anodes and electrolytes.Mg atoms enter the lattice of Li atoms,forming solid solution due to the low amount(5 wt%)of Mg.Mg atoms mainly concentrate near the surface of Mg-alloyed Li metal anodes.The reactivity of Mg-alloyed Li metal is mitigated kinetically,which results from the electron transfer from Li to Mg atoms due to the electronegativity difference.Based on quantitative experimental analysis,the consumption rate of active Li and electrolytes is decreased by using Mgalloyed Li metal anodes,which increases the cycle life of Li metal batteries under demanding conditions.Further,a pouch cell(1.25 Ah)with Mg-alloyed Li metal anodes delivers an energy density of 340 Wh kg^(-1)and a cycle life of 100 cycles.This work inspires the strategy of modifying Li metal anodes to kinetically mitigate the side reactions with electrolytes.

Efficient single-pixel imaging encrypted transmission based on 3D Arnold transformation

Single-pixel imaging(SPI)can transform 2D or 3D image data into 1D light signals,which offers promising prospects for image compression and transmission.However,during data communication these light signals in public channels will easily draw the attention of eavesdroppers.Here,we introduce an efficient encryption method for SPI data transmission that uses the 3D Arnold transformation to directly disrupt 1D single-pixel light signals and utilizes the elliptic curve encryption algorithm for key transmission.This encryption scheme immediately employs Hadamard patterns to illuminate the scene and then utilizes the 3D Arnold transformation to permutate the 1D light signal of single-pixel detection.Then the transformation parameters serve as the secret key,while the security of key exchange is guaranteed by an elliptic curve-based key exchange mechanism.Compared with existing encryption schemes,both computer simulations and optical experiments have been conducted to demonstrate that the proposed technique not only enhances the security of encryption but also eliminates the need for complicated pattern scrambling rules.Additionally,this approach solves the problem of secure key transmission,thus ensuring the security of information and the quality of the decrypted images.

Global research trends in postoperative ileus from 2011 to 2023:A scientometric study

BACKGROUND Postoperative ileus(POI)is a common complication after abdominal surgery with high morbidity,which hinders patient recovery,prolongs hospitalization,and increases healthcare costs.Therefore,POI has become a global public health challenge.POI triggering is multifactorial.Autonomic and hormonal mechanisms are generally involved in POI pathogenesis.Recent studies have shown that beta adrenergic signaling of enteric glia is a POI trigger.Currently,the status quo,trends,and frontiers of global research on POI remain unclear.AIM To explore the current status,trends,and frontiers of POI research from 2011 to the present based on bibliometric analysis.METHODS Publications published on POI research from 2011 to 2023 were retrieved on June 1,2023,from the Web of Science Core Collection.CiteSpace 6.2.R2 and VOSviewer were used to conduct bibliometric visualization.RESULTS In total,778 POI records published from 2011 to 2023 were retrieved.Over the past few decades,the annual cumulative number of related articles has linearly increased,with China and the United States of America contributing prominently.All publications were from 59 countries and territories.China and the University of Bonn were the top contributing country and institution,respectively.Neurogastroenterology&Motility was the most prolific journal.The Journal of Gastrointestinal Surgery had the highest number of citations.Wehner Sven was the most productive author.Burst keywords(e.g.,colon,prolonged ileus,acupuncture,paralytic ileus,pathophysiology,rectal cancer,gastrointestinal function,risk)and a series of reference citation bursts provided evidence for the research frontiers in recent years.CONCLUSION This study demonstrates trends in the published literature on POI and provides new insights for researchers.It emphasizes the importance of multidisciplinary cooperation in the development of this field.

前交叉韧带直接止点不同股骨隧道定位解剖位置单束重建对髌股关节退变的影响

目的对比前交叉韧带直接止点不同股骨隧道定位解剖位置单束重建对髌股关节退变的影响。方法选取2016年2月—2021年3月蚌埠市第三人民医院收治的前交叉韧带损伤患者50例的临床资料。根据前交叉韧带重建术中单束重建的股骨隧道定位解剖位置不同分为研究组(在髁间窝外侧壁、原前交叉韧带足印中心方向置入克氏针)26例,对照组(在髁间窝外侧壁过顶点远端7 mm处置入克氏针)24例。自手术治疗起随访两组患者12个月。统计两组患者手术及恢复情况,比较两组患者手术前后疼痛、膝关节功能、膝关节稳定性、髌股关节退变情况,统计术后并发症。结果两组患者手术时间、扶拐下地负重时间、弃拐完全下地负重时间比较,差异均无统计学意义(P>0.05)。研究组与对照组患者术前、术后3个月、术后6个月、术后12个月的疼痛视觉模拟评分(VAS)比较,采用重复测量设计的方差分析,结果:①不同时间点VAS评分有差异(F=12.098,P=0.000);②研究组与对照组VAS评分无差异(F=0.895,P=0.403);③两组VAS评分变化趋势无差异(F=0.715,P=0.456)。研究组患者术前与术后12个月国际膝关节评分委员会(IKDC)评分、Lysholm评分的差值高于对照组(P<0.05)。研究组患者术前与术后12个月KT1000膝关节移动度的差值、轴移试验阳性减少率均高于对照组(P<0.05)。研究组与对照组患者术前髌股关节退变Recht分级比较,差异无统计学意义(P>0.05);研究组患者术后12个月髌股关节退变Recht分级优于对照组(P<0.05)。对照组患者术后12个月的髌股关节退变Recht分级差于术前(P<0.05)。研究组患者术前与术后12个月的髌股关节退变Recht分级比较,差异无统计学意义(P>0.05)。两组患者总并发症发生率比较,差异无统计学意义(P>0.05)。结论不同股骨隧道定位解剖位置的单束重建与髌股关节退变有关,在髁间窝外侧壁、原前交叉韧带足印中心方向置入克氏针的单束重建可使患者获得更佳的膝关节功能及膝关节稳定性,且术后髌股关节软骨退变程度更小。

橡皮链法与牵引钩滑动法关闭拔牙病例治疗后期前牙散在间隙的疗效观察

目的评价分析橡皮链法和牵引钩滑动法关闭前牙散在间隙的临床疗效。方法选取2014年7月-2015年3月该院口腔科就诊的拔除双侧第一前磨牙进行固定矫治的牙颌畸形患者80例。所有患者随机平均分为A、B组。拔牙间隙关闭后,分别采用橡皮链法(A组)和牵引钩滑动法(B组)关闭前牙间隙,施力大小均为150 g。每月复诊更换橡皮链,通过石膏模型记录测量出间隙变化值,直到间隙完全关闭。比较橡皮链法及牵引钩滑动法关闭间隙的效果和速度、成人和青少年间隙关闭的速度。结果两种方法关闭前牙间隙都能达到预期疗效,未出现不良反应。橡皮链法关闭间隙的平均速度为1.17 mm/月,牵引钩滑动法的平均速度为0.90 mm/月。橡皮链法关闭前牙间隙的速度快于牵引钩滑动法(P <0.05)。青少年间隙关闭的速度较成年人快(P <0.05)。结论使用橡皮链法关闭前牙间隙是一种较为高效的间隙关闭方式,具有良好的临床推广价值。

Nogo-A aggravates oxidative damage in oligodendrocytes

Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system.It is mainly expressed by oligodendrocytes.Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition,neuronal homeostasis,precursor migration,plasticity,and neurodegeneration,its functions in the process of oxidative injury are largely uncharacterized.In this study,oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats.We used hydrogen peroxide(H2O2)to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes.After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes,Nogo-A expression was increased,and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death.Furthermore,knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H2O2.Intervention with a Nogo-66 antibody,a LINGO1 blocker,or Y27632,an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway,did not affect the death of oligodendrocytes.Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes.In conclusion,Nogo-A aggravated reactive oxygen species damage in oligodendrocytes,and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process.This study was approved by the Ethics Committee of Peking University People’s Hospital,China(approval No.2018PHC081)on December 18,2018.

Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus

BACKGROUND Esophageal adenocarcinoma(EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus(BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated.AIM To explore the transcriptome changes in the progression from normal esophagus(NE) to BE and EAC.METHODS Two datasets from the Gene Expression Omnibus(GEO) in NCBI Database(https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes(DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery(DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets.RESULTS In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors(DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs,E2 F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2 C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1 A1 could discriminate EAC from NE tissue, while REG1 A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1 A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer.CONCLUSION After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1 A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.

Beta 2-adrenergic receptor activation enhances neurogenesis in Alzheimer's disease mice

Impaired hippocampal neurogenesis is one of the early pathological features of Alzheimer＇s disease. Enhancing adult hippocampal neuro- genesis has been pursued as a potential therapeutic strategy for Alzheimer＇s disease. Recent studies have demonstrated that environmental novelty activates β2-adrenergic signaling and prevents the memory impairment induced by amyloid-β oligomers. Here, we hypothesized that β2-adrenoceptor activation would enhance neurogenesis and ameliorate memory deficits in Alzheimer＇s disease. To test this hypothe- sis, we investigated the effects and mechanisms of action of β2-adrenoceptor activation on neurogenesis and memory in amyloid precursor protein/presenilin 1 （APP/PS1） mice using the agonist clenbuterol （intraperitoneal injection, 2 mg/kg）. We found that β2-adrenoceptor ac- tivation enhanced hippocampal neurogenesis, ameliorated memory deficits, and increased dendritic branching and the density of dendritic spines, lhese effects were associated with the upregulation of postsynaptic density 95, synapsin 1 and synaptophysin in APP/PS1 mice. Furthermore, β2-adrenoceptor activation decreased cerebral amyloid plaques by decreasing APP phosphorylation at Thr668. These findings suggest that β2-adrenoceptor activation enhances neurogenesis and ameliorates memory deficits in APP/PS 1 mice.

Building the Stable Oxygen Framework in High-Ni Layered Oxide Cathode for High-Energy-Density Li-Ion Batteries

High-Ni layered oxide cathodes hold a great promise for fabricating highenergy lithium-ion batteries.However,the oxygen evolution during cycling is a crucial factor in the structure deterioration,potential change,and capacity decay of cathodes,limiting the commercial application of high-Ni(Ni>0.9)layered oxides in batteries.Herein,we demonstrate a feasible approach to enhance the stability of oxygen framework,through the surface oxygen immobilization with yttrium and bulk oxygen stabilization with aluminum in high-Ni layered oxides.As expected,benefiting from the oxygen-stabilized framework,the bulk structure deterioration,and interfacial parasitic reaction are mitigated obviously during battery operation,along with the improved thermal stability of cathode.Correspondingly,the as-prepared high-Ni oxide delivers high reversible capacity,impressive cycle ability,and low potential polarization upon cycling.Such significant improvement on the electrochemical performance is primarily attributed to the strong oxygen affinities of both yttrium at the surface layer and aluminum in the bulk,which synergistically stabilizes the oxygen framework of high-Ni oxide via raising the energy barrier for oxygen evolution.Therefore,building the stable oxygen framework is critical for enhancing the energy density output,cycle operation,and thermal stability of high-Ni oxide cathodes.

Formation mechanism of asymmetric breather and rogue waves in pair-transition-coupled nonlinear Schr?dinger equations

Based on the developed Darboux transformation, we investigate the exact asymmetric solutions of breather and rogue waves in pair-transition-coupled nonlinear Schr?dinger equations. As an example, some types of exact breather solutions are given analytically by adjusting the parameters. Moreover, the interesting fundamental problem is to clarify the formation mechanism of asymmetry breather solutions and how the particle number and energy exchange between the background and soliton ultimately form the breather solutions. Our results also show that the formation mechanism from breather to rogue wave arises from the transformation from the periodic total exchange into the temporal local property.

Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer

Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addition,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSALDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2%and 94.8%,respectively(P<0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.

Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China

BACKGROUND The gut microbiota(GM)has been proven to play a role in the regulation of host lipid metabolism,which provides a new theory about the pathogenesis of dyslipidemia.However,the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation.AIM To investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population.METHODS This study ultimately recruited 142 participants(73 females and 69 males)at Honghui Hospital,Xi’an Jiaotong University.The anthropometric and blood metabolic parameters of all participants were measured.According to their serum lipid levels,female and male participants were classified into a high triglyceride(H_TG)group,a high total cholesterol(H_CHO)group,a low high-density lipoprotein cholesterol(L_HDL-C)group,and a control(CON)group with normal serum lipid levels.Fresh fecal samples were collected for 16S rRNA gene sequencing.UPARSE software,QIIME software,the RDP classifier and the FAPROTAX database were used for sequencing analyses.RESULTS The GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM.Different GM features were identified between females and males,and the associations between GM and serum lipid profiles were different in females and males.The GM features in different dyslipidemia subgroups changed in both female patients and male patients.Proteobacteria,Lactobacillaceae,Lactobacillus and Lactobacillus_salivarius were enriched in H_CHO females compared with CON females,while Coriobacteriia were enriched in L_HDL-C females.In the comparison among the three dyslipidemia subgroups in females,Lactobacillus_salivarius were enriched in H_CHO females,and Prevotellaceae were enriched in L_HDL-C females.Compared with CON or H_TG males,Prevotellaceae,unidentified_Ruminococcaceae,Roseburia and Roseburia_inulinivorans were decreased in L_HDL-C males(P value<0.05),and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H_TG males compared with other male subgroups.Additionally,Roseburia_inulinivorans abundance was positively correlated with serum TG and total cholesterol levels,and Roseburia were positively correlated with serum TG level.Furthermore,Proteobacteria(0.724,95%CI:0.567-0.849),Lactobacillaceae(0.703,95%CI:0.544-0.832),Lactobacillus(0.705,95%CI:0.547-0.834)and Lactobacillus_salivarius(0.706,95%CI:0.548-0.835)could distinguish H_CHO females from CON females,while Coriobacteriia(0.710,95%CI:0.547-0.841),Coriobacteriales(0.710,95%CI:0.547-0.841),Prevotellaceae(0.697,95%CI:0.534-0.830),Roseburia(0.697,95%CI:0.534-0.830)and Roseburia_inulinivorans(0.684,95%CI:0.520-0.820)could discriminate H_TG males from CON males.Based on the predictions of GM metabolic capabilities with the FAPROTAX database,a total of 51 functional assignments were obtained in females,while 38 were obtained in males.This functional prediction suggested that cellulolysis increased in L_HDL-C females compared with CON females,but decreased in L_HDL-C males compared with CON males.CONCLUSION This study indicates associations of GM with serum lipid profiles,supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia,and sex differences should be considered.

From Diabetes to Diabetic Complications:Role of Autophagy

Diabetes and its complications reduce quality of life and are life-limiting.At present,diabetes treatment consists of hypoglycemic agents to control blood glucose and the use of insulin-sensitizing drugs to overcome insulin resistance.In diabetes,autophagy is impaired and thus there is poor intracellular environment homeostasis.Pancreaticβ-cells and insulin target tissues are protected by enhancing autophagy.Autophagy decreasesβ-cell apoptosis,promotesβ-cell proliferation,and alleviates insulin resistance.Autophagy in diabetes is regulated by the mammalian target of rapamycin(mTOR)/adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)pathway and others.Autophagy enhancers can likely be used as a treatment for diabetes and its complications.This review examines the evidence linking autophagy to diabetes.

Mechanisms of action of natural products on type 2 diabetes

Over the past several decades,type 2 diabetes mellitus(T2DM)has been considered a global public health concern.Currently,various therapeutic modalities are available for T2DM management,including dietary modifications,moderate exercise,and use of hypoglycemic agents and lipid-lowering medications.Although the curative effect of most drugs on T2DM is significant,they also exert some adverse side effects.Biologically active substances found in natural medicines are important for T2DM treatment.Several recent studies have reported that active ingredients derived from traditional medicines or foods exert a therapeutic effect on T2DM.This review compiled important articles regarding the therapeutic effects of natural products and their active ingredients on isletβcell function,adipose tissue inflammation,and insulin resistance.Additionally,this review provided an in-depth understanding of the multiple regulatory effects on different targets and signaling pathways of natural medicines in the treatment of T2DM as well as a theoretical basis for clinical effective application.

Primary intracranial synovial sarcoma with hemorrhage:A case report

BACKGROUND Synovial sarcoma(SS)is a highly malignant tumor of unknown histological origin.This tumor can occur in various parts of the body,including those without synovial structures,but mainly in and around the joints,mostly in the lower extremities.Primary intracranial SSs are remarkably rare.This paper aims to report a case of primary intracranial SS with hemorrhage.CASE SUMMARY A 35-year-old male patient suffered a headache and slurred speech during manual labor and was sent to the emergency department.Through imaging examination,the patient was considered to have high-grade glioma complicated with hemorrhage and was treated with craniotomy.Postoperative pathology revealed SS.positron emission tomography/computed tomography was performed,which ruled out the possibility of metastasis to the intracranial from other parts of the body.Postoperative radiotherapy was given to the patient,during which radiation necrosis occurred.Sixteen months after craniotomy,cranial magnetic resonance imaging revealed recurrence of the tumor.CONCLUSION Primary intracranial SS is a rare malignant tumor.Primary intracranial SS with hemorrhage and radiation necrosis should be carefully monitored during postoperative radiotherapy.Surgical resection of the tumor combined with postoperative radiotherapy and chemotherapy is currently used,but the prognosis is poor.

基于随动控制的蜗杆检测系统设计（英文）

This paper presents a detection method for hourglass worm based on follow-up pre-positioning technolo-gy, by establishing theoretical model of the corresponding relation between the movements of the worm and theprobe. The probe coordinate of next sample point is mapped through the actual motion coordinate measured ateach sample point. And then the probe is located to the next sample point in advance by using the precision mo-tion control based on time subdivision. This detection method can realize online servo measurement for machiningerror of hourglass worm and actual space spiral measurement under specific throat radius. The actual surface con-tour of hourglass worm is constructed by helixes in different throat radiuses, then the machining error can be ob-tained by comparing the contour with theoretical model. The detection system, which includes host and slave sub-systems, is designed according to this method.

Incontinentia pigmenti with intracranial arachnoid cyst: A case report

BACKGROUND Incontinentia pigmenti(IP)is a rare X-linked dominant genetic disorder that can be fatal in male infants.It is a disease that affects many systems of the human body.In addition to characteristic skin changes,patients may also have pathological features of the eyes,teeth,and central nervous system.Therefore,the lesions in these systems may be the first symptoms for which patients seek treatment.To date,no cases of IP complicated by intracranial arachnoid cyst(IAC)have been reported.This paper aims to report a case of IP with IAC in order to share the diagnosis and treatment experience of this rare case with other clinicians.CASE SUMMARY An 11-year-old female patient suffered intermittent limb convulsions for five months and was sent to hospital.In the initial stage,the patient was considered to have primary epilepsy.Further investigation of the patient's medical history,physical examination and imaging examination led to the diagnosis of IP combined with intracranial space-occupying lesions,and secondary epilepsy.The patient was treated with craniotomy,and postoperative pathology revealed an IAC.The patient recovered well after craniotomy and had no obvious surgeryrelated complications.During the follow-up period,the patient did not have recurrent epilepsy symptoms.CONCLUSION IP is a multi-system disease that presents with typical skin lesions at birth,but the long-term prognosis of this disease depends on the involvement of systems other than the skin,especially nervous system and ocular lesions.

Adrenocorticotropic hormone combined with magnesium sulfate therapy for infantile epileptic spasms syndrome:a real-world study

Background Infantile epileptic spasms syndrome(IESS)is a serious disease in infants,and it usually evolves to other epilepsy types or syndromes,especially refractory or super-refractory focal epilepsies.Although adrenocorticotropic hormone(ACTH)is one of the first-line and effective treatment plans for IESS,it has serious side effects and is not sufficiently effective.Methods A retrospective study of the clinical outcomes of ACTH combined with magnesium sulfate(MgSO_(4))therapy for IESS in two hospital centers was conducted.The major outcome of the single and combined treatment was evaluated by changes in seizure frequency and improvements in hypsarrhythmia electroencephalography(EEG).To reduce the confounding bias between the two groups,we used SPSS for the propensity score matching(PSM)analysis.Results We initially recruited 1205 IESS patients from two Chinese hospitals and treated them with ACTH combined with MgSO_(4) and ACTH alone.Only 1005 patients were enrolled in the treatment(ACTH combined with MgSO_(4):744,ACTH:261),and both treatment plans had a more than 55% response rate.However,compared to patients treated with ACTH alone,those patients treated with ACTH combined with MgSO_(4) had better performance in terms of the seizure frequency and hypsarrhythmia EEG.After PSM,the two groups also showed significant differences in responder rate[70.8%(95% confidence interval,CI)=66.7%–74.8%)vs.53.8%(95%CI=47.4%–60.2%),P<0.001],seizure frequency(P<0.001)and hypsarrhythmia EEG resolution(P<0.001).Notably,multivariate analysis revealed that the lead time to treatment and the number of antiseizure medications taken before treatment were two factors that may affect the clinical outcome.Patients with less than 3 months of lead time responded to the treatment much better than those with>3 months(P<0.05).In addition,the overall incidence of adverse reactions in the ACTH combined with MgSO_(4) group was much lower than that in the ACTH group(31.4%vs.63.1%,P<0.001).During the treatment,only infection(P=0.045)and hypertension(P=0.025)were significantly different between the two groups,and no baby died.Conclusion Our findings support that ACTH combined with MgSO_(4) is a more effective short-term treatment protocol for patients with IESS than ACTH alone,especially for those patients with short lead times to treatment.

Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy

This was a single-arm,multicenter,open-label phase I trial.Lentiviral vectors(LV)carrying the ABCD1 gene(LV-ABCD1)was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy(CCALD),and multi-site injection was performed.The injection dose increased from 200 to 1600 lL(vector titer:1×10^(9) transduction units per mL(TU/mL)),and the average dose per kilogram body weight ranges from 8 to 63.6 lL/kg.The primary endpoint was safety,dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein.A total of 7 patients participated in this phase I study and were followed for 1 year.No injectionrelated serious adverse event or death occurred.Common adverse events associated with the injection were irritability(71%,5/7)and fever(37.2-38.5℃,57%,4/7).Adverse events were mild and selflimited,or resolved within 3 d of symptomatic treatment.The maximal tolerable dose is 1600 lL.In 5 cases(83.3%,5/6),no lentivirus associated antibodies were detected.The overall survival at 1-year was 100%.The ABCD1 protein expression was detected in neutrophils,monocytes and lymphocytes.This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo;even the maximal dose did not increase the risk of adverse events.Furthermore,the direct LV-ABCD1 injection displayed low immunogenicity.In addition,the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed.This study has been registered in the Chinese Clinical Trial Registry(https://www.chictr.org.cn/,registration number:ChiCTR1900026649).

Sirolimus can promote the disappearance of renal angiomyolipoma associated with tuberous sclerosis complex:a prospective cohort study

Background Renal angiomyolipoma(RAML)is the most common kidney lesion in patients with tuberous sclerosis complex(TSC),affecting about 80%of patients.It is a benign tumor that grows over time,usually bilaterally,and can easily lead to kidney complications such as acute hemorrhage.Herein,we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup analysis.Methods A prospective cohort study was conducted.Sirolimus was initiated at 1 mg/(m^(2)×day),and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/mL.The disappearance of RAML in chil-dren after sirolimus treatment was observed,and Cox regression was used to screen the factors affecting tumor disappearance.Results One hundred and twenty-six patients who met the criteria were analyzed.After 3 months,6 months,12 months,and 24 months of follow-up,tumors disappeared in 18(14.3%),30(23.8%),39(31.0%),and 42(33.3%)children,respec-tively.Tumors disappeared in 50(39.7%)children by the last visit of each individual,and 30(60%)of them occurred within 6 months.The multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance rate.Thirty-six(29%)patients had stomatitis during the entire treatment period,and no serious adversereactionswereobserved.Conclusions Sirolimus could promote the disappearance of TSC-related RAML.The disappearance rate was correlated with the maximum diameter at baseline,and the smaller the tumor was,the higher the disappearance rate.It is well tolerated in the treatment of RAML associated with TSC.