Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

EZH2-dependent myelination following sciatic nerve injury

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.

3D printing in space:from mechanical structures to living tissues

3D printing stands at the forefront of transforming space exploration,offering unprecedented on-demand and rapid manufacturing capabilities.It adeptly addresses challenges such as mass reduction,intricate component fabrication,and resource constraints.Despite the obstacles posed by microgravity and extreme environments,continual advancements underscore the pivotal role of 3D printing in aerospace science.Beyond its primary function of producing space structures,3D printing contributes significantly to progress in electronics,biomedicine,and resource optimization.This perspective delves into the technological advantages,environmental challenges,development status,and opportunities of 3D printing in space.Envisioning its crucial impact,we anticipate that 3D printing will unlock innovative solutions,reshape manufacturing practices,and foster self-sufficiency in future space endeavors.

Comparative analysis shows high level of lineage sorting in genomic regions with low recombination in the extended Picea likiangensis species complex

Genome-scale data,while promising for illuminating phylogenetic relationships,frequently pose a conundrum by yielding conflicting topologies and highly variable gene tree distributions(Pease et al.,2016).This complexity likely arises from the reticulate evolution observed in many taxa,where genetic information exchange occurs through diverse biological processes.

Spectral Index Distribution of Various Scale Components in Supernova Remnant Cassiopeia A

Cassiopeia A(Cas A) is a well-known candidate for studying cosmic-ray acceleration, in which compact features of various scales have attracted much attention. Based on observations by the Very Large Array of Cas A at 6 cm and 21 cm, we measure the spectral index distribution of various scale components using the observation of the 1998 epoch. We decompose its total density image into nine scale components, and map the temperature spectral index distribution of each component, which ranges from-2.48 ± 0.01 to-2.91 ± 0.05. We find that the spectral indices increase from the small scale to large scale components. A damped post-shock magnetic field model with a strength larger than ~200 μG and a damping length scale less than ~10% of the remnant radius can account for the spectral index variation naturally.

SPOT屈光筛查仪在6岁以下儿童视力筛查的转诊标准研究

目的:基于2021版美国斜视与小儿眼科协会(AAPOS)《儿童视力筛查指南》,修订SPOT屈光筛查仪在6岁以下儿童的转诊标准,并评估其准确性。方法:纳入2022-01/2023-04在南京市雨花台区妇幼保健所就诊的儿童,进行SPOT屈光筛查仪、睫状肌麻痹检影验光等检查,并根据AAPOS指南定义具有弱视危险因素(ARFs)及有临床意义屈光不正(VSRE)的目标人群。使用受试者工作曲线计算最佳转诊标准,并与厂商标准、吴标准、Peterseim标准进行对比。结果:共有959名儿童接受检查,其中<4岁组342人,≥4岁组617人。<4岁组的最佳转诊标准为:近视≤-2.75D、远视≥+2.25D、散光≤-2.75D、屈光参差≥1.00D;≥4岁组为近视≤-1.75D、远视≥+2.00D、散光≤-2.25D、屈光参差≥1.00D;其约登指数分别为0.38与0.52,均高于其他标准。结论:采用新的6岁以下儿童屈光筛查转诊标准,其准确性较高,优于既往其他标准,能为儿童眼保健工作提供有益参考。

Functionalized alginate-based bioinks for microscale electrohydrodynamic bioprinting of living tissue constructs with improved cellular spreading and alignment

Bioprinting has been widely investigated for tissue engineering and regenerative medicine applications.However,it is still difficult to reconstruct the complex native cell arrangement due to the limited printing resolution of conventional bioprinting techniques such as extrusion-and inkjet-based printing.Recently,an electrohydrodynamic(EHD)bioprinting strategy was reported for the precise deposition of well-organized cell-laden constructs with microscale filament size,whereas few studies have been devoted to developing bioinks that can be applied for EHD bioprinting and simultaneously support cell spreading.This study describes functionalized alginate-based bioinks for microscale EHD bioprinting using peptide grafting and fibrin incorporation,which leads to high cell viability(>90%)and cell spreading.The printed filaments can be further refined to as small as 30μm by incorporating polyoxyethylene and remained stable over one week when exposed to an aqueous environment.By utilizing the presented alginate-based bioinks,layer-specific cell alignment along the printing struts could be observed inside the EHD-printed microscale filaments,which allows fabricating living constructs with cell-scale filament resolution for guided cellular orientation.

3D printing of functional bioengineered constructs for neural regeneration: a review

Three-dimensional(3D)printing technology has opened a new paradigm to controllably and reproducibly fabricate bioengineered neural constructs for potential applications in repairing injured nervous tissues or producing in vitro nervous tissue models.However,the complexity of nervous tissues poses great challenges to 3D-printed bioengineered analogues,which should possess diverse architectural/chemical/electrical functionalities to resemble the native growth microenvironments for functional neural regeneration.In this work,we provide a state-of-the-art review of the latest development of 3D printing for bioengineered neural constructs.Various 3D printing techniques for neural tissue-engineered scaffolds or living cell-laden constructs are summarized and compared in terms of their unique advantages.We highlight the advanced strategies by integrating topographical,biochemical and electroactive cues inside 3D-printed neural constructs to replicate in vivo-like microenvironment for functional neural regeneration.The typical applications of 3D-printed bioengineered constructs for in vivo repair of injured nervous tissues,bio-electronics interfacing with native nervous system,neural-on-chips as well as brain-like tissue models are demonstrated.The challenges and future outlook associated with 3D printing for functional neural constructs in various categories are discussed.

Classification of metabolic-associated fatty liver disease subtypes based on TCM clinical phenotype

Objective:To classify the subtypes of metabolic-associated fatty liver disease(MAFLD)and provide new insights into the heterogeneity of MAFLD.Methods:Electronic medical records(EMR)of MAFLD diagnosed in accordance with the diagnostic criteria of Hubei Provincial Hospital of Traditional Chinese Medicine from 2016-2020 were included in the study.for physical annotation,and the data on each clinical phenotype was normalized according to corresponding aspirational standards.The MAFLD heterogeneous medical record network(HEMnet)was constructed using sex,age,disease diagnosis,symptoms,and Western medicine prescriptions as nodes and the co-occurrence times between phenotypes as edges.K-means clustering was used for disease classification.Relative risk(RR)was used to assess the specificity of each phenotype.Statistical methods were used to compare differences in laboratory indicators among subtypes.Results:A total of patients(12,626)with a mean age of 55.02(±14.21)years were included in the study.MAFLD can be divided into five subtypes:digestive diseases(C0),mental disorders and gynecological diseases(C1),chronic liver diseases and decompensated complications(C2),diabetes mellitus and its complications(C3),and immune joint system diseases(C4).Conclusions:Patients with MAFLD experience various symptoms and complications.The classification of MAFLD based on the HEMnet method is highly reliable.

Acute penetrating injury of the spinal cord by a wooden spike with delayed surgery:a case report

Rarely,penetrating injuries to the spinal cord result from wooden objects,creating unique challenges to mitigate neurological injury and high rates of infection and foreign body reactions.We report a man who sustained a penetrating cervical spinal cord injury from a sharpened stick.While initially tetraparetic,he rapidly recovered function.The risks of neurological deterioration during surgical removal made the patient reluctant to consent to surgery despite the impalement of the spinal cord.A repeat MRI on day 3 showed an extension of edema indicating progressive inflammation.On the 7~(th)day after injury,fever and paresthesias occurred with a large increase in serum inflammatory indicators,and the patient agreed to undergo surgical removal of the wooden object.We discuss the management nuances related to wood,the longitudinal evolution of MRI findings,infection risk,surgical risk mitigation and technique,an inflammatory marker profile,long-term recovery,and the surprisingly minimal neurological deficits associated with low-velocity midline spinal cord injuries.The patient had an excellent clinical outcome.The main lessons are that a wooden penetrating central nervous system injury has a high risk for infection,and that surgical removal from the spinal cord should be performed soon after injury and under direct visualization.

Impact of twice-a-day transcranial direct current stimulation intervention on cognitive function and motor cortex plasticity in patients with Alzheimer's disease

Background Non-invasive brain stimulation has improved cognitive functions in patients with Alzheimer's disease(AD),and some studies suggest a close relationship between cognition and plasticity.However,the clinical benefits of transcranial direct current stimulation(tDCS)in patients still need to be evaluated.Aims This study examined the role of tDCS in improving cognition and whether the improved cognition is related to altered cortical plasticity.Methods 124 patients with AD were randomly assigned to active tDCS(n=63)or sham tDCS(n=61).The tDCS was applied at the dorsolateral prefrontal cortex for 30 treatment sessions across 6 weeks(5 days per week,2 days off).The Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-Cognitive(ADAS-Cog)were used for cognition evaluation at baseline,week 2 and week 6.The cortical plasticity was represented by motor-evoked potential(MEP)measured with an electromyogram.Results The results showed thatmultiplecourses of active tDcS can improve the cognitive functions of patients with AD,especially in the memory domain(word recall,recall of test instructions and word recognition).In addition,the damaged MEP level was enhanced following active treatment.In the active tDCS group,the improvements in ADAS-Cog total and subitem(word recall and word recognition)scores were negatively correlated with the enhancement of MEP.Conclusions Our research indicates for the first time that twice-a-day tDS may improve the cognitive function of patients with AD.This study also suggests that cognitive dysfunction may be related to impaired cortical plasticity,which warrants mechanistic investigations of the relationship between cognition and plasticity in the future.

Network Pharmacology, Molecular Docking and Experimental Exploring Molecular Mechanisms of Yinqiao Anti-Epidemic Formula in Regulating Mucosal Immune System of Respiratory Tract

[Objectives]To explore the molecular mechanisms of Yinqiao anti-epidemic formula(YQAEF)in regulating mucosal immune system of respiratory tract.[Methods]The active components of YQAEF were obtained from the TCMSP database,and RMIS targets were obtained from the GeneCards database.A"YQAEF components-RMIS targets-pathways"network was constructed by analyzing the above data to screen core targets for molecular docking verification.A mouse model of acute upper respiratory tract infection(AURI)was developed.Based on the experimental models,the key pathway target genes screened by network pharmacology were verified in vivo.[Results]The main active components of YQAEF involved in the regulation of the RMIS included quercetin,acetic acid,and raffinose.Key targets,such as angiotensin-converting enzyme(ACE),galactosidase alpha(GLA),matrix metalloproteinase 2(MMP2),Serpin Family E Member 1(SERPINE1),and myeloperoxidase(MPO)and important viral infection and endocrine resistance signaling pathways were included in the regulation of the RMIS with YQAEF.Molecular docking assays showed that the key targets had good binding activities with the components of YQAEF.Based on the results of network pharmacology,key target proteins in ACE,GLA,MMP2,SERPINE1,and MPO were selected for experimental verification.The results showed that ACE/ACE2 and MPO expressions were increased in the oral and throat mucosa of the AURI mice.Under YQAEF treatment,the expression levels of ACE/ACE2 and MPO were decreased.[Conclusions]This study revealed the mechanism of YQAEF in the regulation of RMIS,which is associated with multiple components,targets,and pathways.Further experiments confirmed that YQAEF interfered with MPO and ACE/ACE2 signaling pathways to regulate the RMIS in the oral and throat mucosa tissue of mice with AURI,and provide a new direction for exploring the potential antiviral mechanism of YQAEF.

碱烧伤诱导兔部分性角膜缘干细胞失代偿模型

目的:探讨诱导兔部分性角膜缘干细胞失代偿(limbal stem cell deficiency,LSCD)动物模型的一种新方法。方法:分别采用C57小鼠和新西兰白兔制作完全性和部分性角膜缘干细胞失代偿动物模型。小鼠(n=30)采用1mol/L氢氧化钾溶液浸泡的滤纸片(直径3mm)置于左眼中央角膜表面30s,随后用生理盐水冲洗。白兔(n=19)切除瞬膜(第三眼睑)后,采用1mol/L氢氧化钾溶液浸泡的滤纸片(直径5mm)置于左眼颞上方角膜表面30s,随后用生理盐水冲洗。烧伤眼术后采用0.5%盐酸左氧氟沙星滴眼液4次/d。烧伤前、烧伤后第1、2、4wk,2mo采用裂隙灯显微镜观察、摄像,记录角膜溃疡、穿孔等并发症。术后2mo采用印迹细胞学检测角膜杯状细胞分布,根据裂隙灯显微镜检查所见和角膜印迹细胞学检查判断LSCD严重程度。术后2mo处死动物,角结膜切片观察角膜新生血管、杯状细胞分布。意外死亡动物不计入总数,计算并比较完全性LSCD和部分性LSCD的模型诱导成功率。结果:30只小鼠中6只意外死亡,2只于烧伤后出现角膜穿孔,其余22只发生完全性LSCD,诱导成功率92%,烧伤后2mo小鼠角膜可见新生血管广泛分布于角膜浅层及深基质层,病理切片可见角膜新生血管。19只白兔,7只意外死亡,其余12只发生不同程度LSCD(部分性LSCD,平均累及1.17±0.39个象限),未发生角膜穿孔情况,诱导成功率100%(P=0.543)。正常角膜区域无杯状细胞,LSCD区域角膜上皮印迹细胞学PAS染色可见杯状细胞,平均密度58.60±12.58个细胞/HP。结论:中央角膜碱烧伤可以诱导产生完全性LSCD,部分动物会因为角膜溃疡穿孔而导致模型诱导失败,LSCD往往比较严重,且合并深层角膜新生血管。颞上方角膜碱烧伤可以诱导产生部分性LSCD,合并较少的角膜病变,角膜新生血管位于浅层。

不同机制所致的血管紊乱化生长的共同干预——安罗替尼治疗右肺鳞癌合并血栓闭塞性脉管炎1例

背景与目的肺目前为止血栓闭塞性脉管炎(thromboangiitis obliterans,TAO,又称Buerger disease)仍无理想的治疗方法。安罗替尼作为三线药物,指南推荐用于二线治疗后复发或进展的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者。分析1例右肺鳞癌合并血栓闭塞性脉管炎的治疗困境及疗效评价,为两种疾病的治疗提供新的思路。方法回顾性分析了上海交通大学附属第一人民医院呼吸与危重症医学科2018年8月收治的1例右肺鳞癌合并血栓闭塞性脉管炎的诊断、治疗过程,并文献复习。结果患者男性,73岁,因"咳嗽、咳痰5月"入院。查体双下肢色素沉着伴足背动脉搏动减弱。既往有吸烟史,可疑血管性间歇性跛行并游走性静脉炎一年余。胸部计算机断层扫描(computed tomography,CT)提示右上肺肿瘤伴阻塞性肺炎,气管镜活检证实为鳞癌;B超提示双上肢及双下肢多发动脉闭塞,下肢深静脉血栓。诊断考虑:右肺鳞癌(T4N2M0,Ⅲb期),体力状况(performance status,PS)评分2分;肺部感染;血栓闭塞性脉管炎。患者外周穿刺置入中心静脉导管(peripherallyinsertedcentral catheter,PICC)和静脉输液岗植入术均失败,无法进行化疗。结合文献检索,考虑TAO也可能存在血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)信号通路紊乱,选择安罗替尼(12 mg qd po)治疗。患者耐受性良好,随访14个月,肺部病变持续空洞化并缩小,同时血栓闭塞性脉管炎好转。结论该患者罹患鳞癌合并TAO,安罗替尼治疗可有效控制肺癌增长,同时改善TAO相关症状。安罗替尼可能通过阻断VEGF信号通路,纠正紊乱化生长的血管,而不仅仅是抑制血管生成。

先天性鼻泪管阻塞的治疗

先天性鼻泪管阻塞(CNLDO)在新生儿中的发病率高达5.7%。目前临床上CNLDO的治疗方式很多,诊疗随意性很大,如何在合适时机选择最佳的治疗方式仍有很多争论。为了解各种治疗方式的特点,更好地服务临床,本文特围绕CNLDO的治疗展开综述。

The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients

Immune checkpoint inhibitors(ICIs)are new and promising therapeutic agents for non-small cell lung cancer(NSCLC).However,along with demonstrating remarkable efficacy,ICIs can also trigger immune-related adverse events.Checkpoint inhibitor pneumonitis(CIP)has been reported to have a morbidity rate of 3%to 5%and a mortality rate of 10%to 17%.Moreover,the incidence of CIP in NSCLC is higher than that in other tumor types,reaching 7%to 13%.With the increased use of ICIs in NSCLC,CIP has drawn extensive attention from oncologists and cancer researchers.Identifying high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse events.In this review,the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease,prior thoracic irradiation,and combinations with other drugs.Our review also explored potential mechanisms closely related toCIP,including increasedT cell activity against associated antigens in tumor and normal tissues,preexisting autoantibodies,and inflammatory cytokines.

Successful endoscopic sclerotherapy for bleeding gastric varices with combined cyanoacrylate and aethoxysklerol

Two patients with liver cirrhosis and portal hyper-tension related to hepatitis infection were admitted to Shanghai Ruijin Hospital due to recurrent melena and hematemesis. Isolated gastric varices were observed in the gastric fundus during the retroflexion of gastroscope. We carried out endoscopic sclerotherapy successfully for bleeding gastric varices with combined cyanoacrylate and aethoxysklerol, which disappeared dramatically several months after two courses of sclerotherapy for each patient. No complication and clinical signs of gastrointestinal re-bleeding were observed during the 6-mo endoscopic follow-up. CT portal angiography (CTPA) has been widely used in the assessment of variceal treatment and improves the results of endoscopic injection therapy.

The potential mechanism, recognition and clinical significance of tumor pseudoprogression after immunotherapy

As immunotherapy has gained increasing interest as a new foundation for cancer therapy,some atypical response patterns,such as pseudoprogression and hyperprogression,have garnered the attention of physicians.Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear,followed by a decrease in tumor burden;this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression.Accurately recognizing pseudoprogression is also a challenge for physicians.Because of the extensive attention on pseudoprogression,significant progress has been made.Some new criteria for immunotherapy,such as irRC,iRECIST and imRECIST,were proposed to accurately evaluate the response to immunotherapy.Many new detection indexes,such as ctDNA and IL-8,have also been used to identify pseudoprogression.In this review,the definition,evaluation criteria,mechanism,monitoring,management and prognosis of pseudoprogression are summarized,and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed;these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.

Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 50α-reductase inhibitor

Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.