Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders

AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were included.Both groups underwent hormone shock therapy during the acute phase.Subsequently,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after treatment.Additionally,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.RESULTS:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(P<0.05),accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio(P<0.05).Moreover,inebilizumab treatment showed a partial effect in preventing optic nerve atrophy(P<0.05).However,there were no significant differences in other therapeutic effects compared to rituximab,which has previously demonstrated substantial therapeutic efficacy(P>0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab injections.CONCLUSION:The combination of inebilizumab and high-dose glucocorticoids proves to be effective.In comparison to rituximab injections,inebilizumab displays better tolerance and safety.Moreover,it demonstrates a partial effect in preventing optic nerve atrophy.Thus,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation

Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional recovery of the injured CNS.Methods:A compressive SCI mouse model was utilized for this investigation.Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein,acrolein-induced inflammation-related factors,and macrophages at the injury site and within the CNS.Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase(PI3K)/AKT pathway to study macrophage regulation.The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67(GAD65/67),vesicular glutamate transporter 1(VGLUT1),paw withdrawal response,and Basso Mouse Scale score.Nissl staining and Luxol Fast Blue(LFB)staining were performed to investigate the structural recovery of the injured CNS.Results:Hydralazine downregulated the levels of acrolein,IL-1β,and TNF-αin the spinal cord.The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway,leading to M2 macrophage polarization,which protected neurons against SCI-induced inflammation.Additionally,hydralazine promoted the structural recovery of the injured spinal cord area.Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression.Furthermore,hydralazine facilitated motor function recovery following SCI.Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.Conclusion:Hydralazine,an acrolein scavenger,significantly mitigated SCI-induced inflammation and oxidative stress in vivo,modulated macrophage activation,and consequently promoted the structural and functional recovery of the injured CNS.

Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52

A major impedance to neuronal regeneration after peripheral nerve injury (PNI) is the activation of various programmed cell death mechanisms in the dorsal root ganglion. Ferroptosis is a form of programmed cell death distinguished by imbalance in iron and thiol metabolism, leading to lethal lipid peroxidation. However, the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear. Ferroportin (Fpn), the only known mammalian nonheme iron export protein, plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis. Here, we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis. We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn, and stimulation of lipid peroxidation. Early administration of the potent arterial vasodilator, hydralazine (HYD), decreases the ubiquitination of Fpn after PNI by binding to UBA52, leading to suppression of neuronal cell death and significant acceleration of axon regeneration and motor function recovery. HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Sonographic evaluation of proximal gastric accommodation in patients with functional dyspepsia

AIM: To assess the value of ultrasonography (US) in evaluation of proximal gastric accommodation disorder in patients with functional dyspepsia (FD). METHODS: Between April 2011 and March 2012, 45 patients with FD and 27 healthy volunteers were enrolled in this study. Two-dimensional ultrasound (2DUS) and 3-dimensional ultrasound (3DUS) were performed sequentially to measure proximal gastric area (PGA), maximal proximal gastric diameter (MPGD), and proximal gastric volume (PGV). These values were measured separately in the two groups every other 5 min for a duration of 25 min after the beginning of ingestion of a test meal. Air pocket grading was done separately for images of 2DUS and blocks of 3DUS obtained at five scanning time points. RESULTS: Both PGA and PGV of patients were significantly smaller than healthy controls (P = 0.000 and 0.002, respectively). Comparing the two parameters between the groups at each time point, the differences were also statistically significant (P = 0.000-0.013), except at 10 min for the PGV (P = 0.077). However, no overall difference was found between the groups in the MPGD measurements (P = 0.114), though it was statistically significant at a 20-minute examination point (P = 0.026). A total of 360 sets or blocks of images were obtained for both 2DUS and 3DUS. For the images analyzed by 2DUS, none were excluded because of gastric gas, and 50 (13.9%) and 310 (86.1%) sets were determined as air pockets grades 1 and 2, respectively. For the images analyzed by 3DUS, 23 (6.4%) blocks were excluded from the measurement due to presence of a large fundus air pocket (grade 3); fifty (13.9%) and 287 (79.7%) blocks were also graded as 1 and 2, respectively. CONCLUSION: Measurement of both PGA and PGV by 2DUS and 3DUS could be useful for assessment of the proximal gastric accommodation.

Association of genotypes of rs671 within ALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas

Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Biomaterials reinforced MSCs transplantation for spinal cord injury repair

Due to the complex pathophysiological mechanism, spinal cord injury (SCI) has become one of the most intractable central nervous system (CNS) diseases to therapy. Stem cell transplantation, mesenchymal stem cells (MSCs) particularly, appeals to more and more attention along with the encouraging therapeutic results for the functional regeneration of SCI. However, traditional cell transplantation strategies have some limitations, including the unsatisfying survival rate of MSCs and their random diffusion from the injection site to ambient tissues. The application of biomaterials in tissue engineering provides a new horizon. Biomaterials can not only confine MSCs in the injured lesions with higher cell viability, but also promote their therapeutic efficacy. This review summarizes the strategies and advantages of biomaterials reinforced MSCs transplantation to treat SCI in recent years,which are clarified in the light of various therapeutic effects in pathophysiological aspects of SCI.

Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes

Traumatic spinal cord injury is a fatal acute event without effective clinical therapies.Following the trauma,immediate neural protection and microenvironment mitigation are vitally important for nerve tissue repair,where stem cell-based therapies could be eclipsed by the deficiency of cells due to the hostile microenvironment as well as the transport and preservation processes.Effective emergency strategies are required to be convenient,biocompatible,and stable.Herein,we assess an emergency cell-free treatment using mesenchymal stem cell-derived exosomes,which have proven capable of comprehensive mitigation of the inhibitory lesion microenvironment.The clinically validated fibrin glue is utilized to encapsulate the exosomes and in-situ gelates in transected rat spinal cords to provide a substrate for exosome delivery as well as nerve tissue growth.The emergency treatment alleviates the inflammatory and oxidative microenvironment,inducing effective nerve tissue repair and functional recovery.The therapy presents a promising strategy for effective emergency treatment of central nervous system trauma。

Incomplete fluid-air exchange technique for idiopathic macular hole surgery

AIM: To explore an improved procedure involving incomplete fluid-air exchange for idiopathic macular hole(IMH), and the closure rate, visual function, and the visual field of macular holes(MHs) were evaluated.METHODS: This prospective randomized controlled study, included 40 eyes of 40 patients with IMH who were treated with pars plana vitrectomy and peeling of the internal limiting membrane. They were grouped by random digital table. Twenty-one eyes underwent incomplete fluidair exchange(IFA) and 19 eyes underwent traditional complete fluid-air exchange(CFA) as the control group. Outcomes included best-corrected visual acuity(BCVA), intraocular pressure, and optical coherence tomography, light adaptive electroretinography, and visual field evaluations.RESULTS: All MHs <400 μm were successfully closed. BCVAs before and 6 mo after surgery were 0.82±0.41 logMAR and 0.28±0.17 logMAR in IFA group and 0.86±0.34 logMAR and 0.34±0.23 logMAR in CFA group, respectively. The electroretinogram analysis of patients in IFA group revealed increases in b-wave amplitudes at 1, 3, and 6 mo after surgery. Additionally, patients in IFA group showed an amplitude increase of 28.6% from baseline at 6 mo(P<0.05), while no obvious improvements were noted in CFA group. Although there were no statistically significant improvements in either group, the IFA group showed a slight increase in mean sensitivity(P>0.05).CONCLUSION: IFA is a reliable method that offers comparable closure rate to CFA and facilitates improvements in visual function.

Fluorescence life-time imaging microscopy(FLIM)monitors tumor cell death triggered by photothermal therapy with MoS_(2) nanosheets

Recently,photothermal therapy(PTT)has been proved to have great potential in tumor therapy.In the last several years,MoS_(2),as one novel member of nanomaterials,has been applied into PTT due to its excellent photothermal conversion efficacy.In this work,we applied fuorescence lifetime imaging microscopy(FLIM)techniques into monitoring the PPT-triggered cell death under MoS_(2) nanosheet treatment.Two types of MoS_(2) nanosheets(single layer nanosheets and few layer nanosheets)were obtained,both of which exhibited presentable photothermal conversion fficacy,leading to high cell death rates of 4T1 cells(mouse breast cancer cells)under PTT.Next,live cell images of 4T1 cells were obtained via directly labeling the mitochondria with Rodamine123,which were then continuously observed with FLIM technique.FLIM data showed that the fuorescence lifetimes of mitochondria targeting dye in cells treated with each type of MoS_(2) nanosheets significantly increased during PTT treatment.By contrast,the fuorescence lifetime of the same dye in control cells(without nanomaterials)remained constant after laser irradiation.These findings suggest that FLIM can be of great value in monitoring cell death process during PTT of cancer cells,which could provide dynamic data of the cellular microenvironment at single cell level in multiple biomedical applications.

Evolution of energy and metal demand driven by industrial revolutions and its trend analysis

Industrial revolutions have a profound impact on energy and metal demand.Based on technological improvement,industrial transformation,and changes of energy and metal consumption in the United States,this paper identified the evolution characteristics of energy and metal demand driven by industrial revolutions,and analyzed the trends of energy and metal demand driven by the fourth industrial revolution which is happening currently.Results indicated that fossil fuels were the major energy sources which boosted up the past three industrial revolutions,whereas their consumption increased at a slowing pace as the economy was growing continually;after the third industrial revolution,the consumption of fossil fuels decoupled gradually with the economic growth.As the industrial structure transformed as the industrial revolutions went on,more and more metals were used in the industries,and the consumption of different metals showed different trends.In recent years,a new technological revolution has surged mainly driven by the overall application of new information technologies.The technological advance in information,new energies,new materials,etc.,will speed up the industrial transformation and exert a deep effect on the demand of energy and metals.It can be inferred that the ratio of clean,non-polluting,renewable energy will rise while the ratio of fossil fuels will drop in the energy demand,and the demand of rare metals will perhaps enter a fast-growing period,while the demand of traditional bulk metals will fluctuate at mid-high levels.Following the new industrial revolution,China should adopt an energy transition strategy of developing low-carbon and free-carbon technologies simultaneously,reinforce the domestic and international metal supply system with the aim of enhancing global governance capability,strengthen the deep development of rich rare metals and broaden the overseas supply channels of scare rare metals.

Fibroadenoma of the Ectopic Axillary Breast Tissue: Sonographic Appearances

Ectopic breast tissue is reported to occur in 0.4% - 6% of women. Breast neoplasms may develop in ectopic breast tissue, as in eutopic breast tissue. The most frequent condition in ectopic breast is breast cancer. Fibroadenomas of ectopic breast tissue have been reported, but are rare. We report two cases of fibroadenomas of ectopic axillary breast tissues. The sonographic appearance of the nodules was spherical and hypoechoic. We found the component of breast tissue near the nodule. It is important to diagnose fibroadenomas of ectopic breast tissue before a histologic examination.

Effect of Reclamation on the Groundwater-Lake Water Interaction in Chen Lake

0 INTRODUCTION To relieve the short supply of suitable land for residing,cultivating,and commerce,it is accepted to reclaim land from lakes,river estuaries,and coastal regions in many countries(Mancini et al.,2020).The large-scale reclamation activities have an irreversible effect on the mico-geomorphology and hydrodynamic system of seasonally flooded areas(Zhang et al.,2019;Yu et al.,2018).For example,coastal regions reclaimed extended the groundwater flow paths,as well as created groundwater level rise,resulting in water-logging in the reclaimed area(Hu et al.,2008).Similar changes in groundwater flow systems may alter groundwater-lake water interactions,and it can ultimately affect the water cycle in the lake areas.However,such detailed studies are presently lacking.In addition,natural exchanges between the lake and groundwater systems can be strongly affected by physical hydrological processes(Javadzadeh et al.,2020),chemical properties(Kamtchueng et al.,2015),and bioto behavior(Hancock et al.,2005).

原始创新从哪里来:再谈化学中费托合成方法的发现

论文从化学史中的费托合成着手,探讨原始创新产生、应用的过程与影响因素。费舍尔(Franz Fischer)和托普施(Hans Tropsch)探索煤制油时发现,费托合成的产物虽复杂但不妨碍它作为液体燃料使用的可行性;随后历时12年开发出实用催化剂,开创了煤间接液化的先河,成为工业催化的经典之作。费托合成案例能帮助研究生树立在工作中另辟蹊径、团队协作的创新理念;也会对研究生培养单位的教师和管理人员有所启发。

早期非小细胞肺癌淋巴结转移规律及清扫方式研究进展

肺癌是目前我国发病率和死亡率均居首位的恶性肿瘤,其中以非小细胞肺癌为主要病理类型。淋巴结转移是非小细胞肺癌最常见和最主要的转移途径,也是影响肺癌分期和预后最重要的因素。由于目前通过现有手段术前很难准确判断早期非小细胞肺癌患者的淋巴结受累情况。因此,在早期非小细胞肺癌中,尤其是在临床I期非小细胞肺癌患者中,淋巴结清扫方式一直存在很大争议。本文就非小细胞肺癌淋巴结转移的规律及清扫方式进行综述。

老年肺癌患者的免疫治疗疗效分析

背景与目的以免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)为代表的免疫疗法成为驱动基因阴性晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的标准治疗方式。但是,肺癌高发于老年患者,而这部分患者很少被纳入重要的临床试验研究。我们旨在研究“真实世界”老年肺癌人群免疫治疗的疗效和安全性。方法回顾性分析2018年7月-2021年10月期间接受免疫治疗的老年NSCLC患者和同期的年轻患者,比较不同年龄分组(<60岁组为中青年组,60岁-74岁为年轻老年组,75岁及以上为一般老年组)患者的客观缓解率(objective response rate,ORR)和无进展生存期(progression-free survival,PFS),并在各年龄亚组中分析不同临床特征对疗效的影响。结果共有21例中青年患者、70例年轻老年患者和15例一般老年患者被纳入本次研究,ORR分别为33.3%、52.8%和53.3%,差异无统计学意义(P=0.284);中位PFS分别9.1个月、7.6个月和10.9个月,差异无统计学意义(P=0.654)。进一步对各亚组免疫治疗的预测因素进行分析,发现在年轻老年组和中青年组中,一线接受免疫治疗的患者的PFS更长。三组不良反应的发生率差异无统计学意义(P>0.05)。结论老年患者接受免疫治疗后的有效性和安全性均与年轻患者相近,一线接受免疫治疗的PFS更长,仍需进一步的前瞻性研究来阐明免疫治疗对老年NSCLC患者的影响。

miR-137, a new target for post-stroke depression?

Expression of miR-137 is downregulated in brain tissue from patients with depression and suicidal behavior, and is also downregulated in peripheral blood from stroke patients. However, it is not yet known if miR-137 acts as a bridge between stroke and depression. To test this, we used middle cerebral artery occlusion and chronic mild stress to establish a post-stroke depression model in rats. Compared with controls, we found significantly lower miR-137 levels in the brain and peripheral blood from post-stroke depression rats. Injection of a miR-137 antagonist into the brain ventricles upregulated miR-137 levels, and improved behavioral changes in post-stroke depression rats. Luciferase assays showed miR-137 bound to the 3＇UTR of Grin2A, regulating Grin2A expression in a neuronal cell line. Grin2A gene overexpression in the brain of post-stroke depression rats, no- ticeably suppressed the inhibitory effect of miR-137 on post-stroke depression. Overall, our results show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby exerting an inhibitory effect on post-stroke depression. Our results offer a new therapeutic direction for post-stroke depression.

Neural Network Based Terminal Sliding Mode Control for WMRs Affected by an Augmented Ground Friction With Slippage Effect

Wheeled mobile robots(WMRs) encounter unavoidable slippage especially on the low adhesion terrain such that the robots stability and accuracy are reduced greatly.To overcome this drawback,this article presents a neural network(NN) based terminal sliding mode control(TSMC) for WMRs where an augmented ground friction model is reported by which the uncertain friction can be estimated and compensated according to the required performance.In contrast to the existing friction models,the developed augmented ground friction model corresponds to actual fact because not only the effects associated with the mobile platform velocity but also the slippage related to the wheel slip rate are concerned simultaneously.Besides,the presented control approach can combine the merits of both TSMC and radial basis function(RBF) neural networks techniques,thereby providing numerous excellent performances for the closed-loop system,such as finite time convergence and faster friction estimation property.Simulation results validate the proposed friction model and robustness of controller;these research results will improve the autonomy and intelligence of WMRs,particularly when the mobile platform suffers from the sophisticated unstructured environment.

Mining the key regulatory genes of chicken inosine 5'-monophosphate metabolism based on time series microarray data

IMP （inosine 5＇-monophosphate） is a compound that enhances the flavor of poultry meat. IMP has become a new breeding trait to improve poultry meat quality. We tried to identify several potential regulatory genes, and construct their predicted regulatory relationships. Time series gene expression profiles of thigh muscle tissues of Rugao chicken, a famous indigenous breed in China, were performed for analysis of genes that are co-expressed or correlated with the concentration of IMP. We found 15 crucial co-expression genes, which are Hspa2, Pten, Gabpa, Bpi, Mkll, Srf,, Cd34, Hspa4, EtvS, Bmpr2, Gdel, IgfbpS, Cd28, Pecam1 and Gja1, that may directly or indirectly regulate IMP metabolism. Eventually, we computed the correlation coefficient between 19 IMP Genes and 15 CGs （15 co-expression genes）, and we identified and constructed a predicted regulation network. In conclusion, variation of IMP concentration was primarily connected with the muscle development process. During this process, 15 CGs were identified that may have significant influence on IMP metabolism. In particular, Bmpr2, Pten and co-expression genes correlated with Entpd8 might play important roles in regulating IMP de novo synthesis, decomposition and salvage synthesis.

Research progress on the role of connective tissue growth factor in fibrosis of diabetic retinopathy

Diabetic retinopathy（DR） is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor（CTGF） is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.

Comparison of Clinical Effects of Au-Pt Based and Ni-Cr Based Porcelain Crowns

Objective To compare the long-term clinical effects of two kinds of crowns and bridges made of porcelain fused to Au-Pt alloy and Ni-Cr alloy. Methods A total of 131 teeth (64 patients) were rehabilitated using porcelain-fused-to-metal crowns, among which 59 were rehabilitated with Au-Pt alloy metal ceramic crown and 72 with Ni-Cr alloy metal ceramic crown. The porcelain fracture, shade, marginal adaptation, gingival discoloration, and gingival status after finishing restoration and 36 months of follow-up were evaluated. Results After 36 months of restoration, porcelain fused to Au-Pt alloy crown showed better clinical effects than porcelain fused to Ni-Cr alloy crown in shade, marginal adaptation, gingival discoloration, as well as gingival status (all P<0.05). Conclusion The Au-Pt alloy ceramic crown is superior to Ni-Cr alloy ceramic crown in long-term clinical effects.