Oral probiotics have emerged as a promising therapeutical strategy for effectively managing ulcerative colitis (UC) in the world. The existing researches successfully preserve probiotic viability in the upper gastrointestinal tract, but they fall short in achieving precise release profile and effective colonization of probiotics at the site of colitis in colon as well as the understanding of therapeutic mechanism with suboptimal efficacy. This constraint poses a significant barrier to rational design and effective development of oral probiotic system. Here, we fabricate an orally layered-by-layered probiotic (Escherichia coli Nissle 1917, EcN) system (so-called CML@EcN) based on carboxymethyl modified lignin (CML) which can significantly protect EcN in gastric and small intestinal microenvironment and efficiently control release EcN in colon. Interestingly, the release and proliferation process of EcN in the colon are detected and can be modeled as a plug-flow mode. We derive a mathematical expression that highly matches the experimental results, providing a theoretical basis for quantitatively calculation of the release process. Furthermore, CML@EcN significantly alleviates symptoms in dextran sulfate sodium (DSS)-induced UC mice by modulating the multiple organ immune disorder and gut microbiota (GM)/metabolites profile as well as reconstructing the colon barrier. Importantly, we explore the mechanism of immune homeostasis regulation via metabolism from GM. Moreover, the CML armour is excreted and would not influence the process. This work not only reports a novel oral therapeutic for UC treatment with high efficacy as well as the exploration of mechanism between GM and immune homeostasis, but also provides a general approach to engineer probiotics for oral administration. ### Competing Interest Statement The authors have declared no competing interest.

Nanovesicle has been extensively investigated and widely used in biomedical applications. However, the premature leakage of water-soluble drugs from nanovesicle seriously limits the further clinical use. It's of great significance to develop effective strategy for leakage inhibition. Herein, we explored effective strategies to prevent drug leakage through coarse-grained molecular simulations. We investigated the influences of doping of cholesteryl hemisuccinate and gold nanoparticles on the morphology and structure of nanovesicle. We found that cholesteryl hemisuccinate can effectively improve the hole defects in the hydrophobic layer to adjust the drug diffusion performance. Then, we studied the effects of particle size, concentration, and surface chemical properties of gold nanoparticles on the drug leakage of nanovesicle. We further verified that the "physical cross-linking" of gold nanoparticles led to more drugs leaking from the nanovesicle cavity. With surface modification, the side effects of "physical cross-linking" were improved with the enhanced dispersion of gold nanoparticles.

Leukocytes play a vital role in immune responses, including defending against invasive pathogens, reconstructing impaired tissue, and maintaining immune homeostasis. When the immune system is activated in vivo, leukocytes accomplish a series of orderly and complex regulatory processes. While cancer and inflammation-related diseases like sepsis are critical medical difficulties plaguing humankind around the world, leukocytes have been shown to largely gather at the focal site, and significantly contribute to inflammation and cancer progression. Therefore, the living leukocyte-based drug delivery systems have attracted considerable attention in recent years due to the innate and specific targeting effect, low immunogenicity, improved therapeutic efficacy, and low reverse effect. In this review, the recent advances in the development of living leukocyte-based drug delivery systems including macrophages, neutrophils, and lymphocytes as promising treatment strategies for cancer and inflammation-related diseases are introduced. The advantages, current challenges, and limitations of these delivery systems are also discussed, as well as perspectives on the future development of precision and targeted therapy in the clinics are provided. Collectively, it is expected that such kind of living cell-based drug delivery system is promising to improve or even revolutionize the treatments of cancers and inflammation-related diseases in the clinics.

Objective: To analyze the health status and radiation sensitivity index of radiation workers in provincial, county and township hospitals. To explore the methods of evaluation indicators, evaluation standards and scoring principles of radiation safety culture in medical institutions.Methods: In 2021, the radiation safety status of all 172 medical institutions in a city was investigated by using retrospective investigation, current situation investigation and laboratory study. The occupational health monitoring data of all 1547 radiation workers were statistically analyzed, and the radiation safety status and health indicators of radiation workers in provincial, county and township level hospitals were compared.Results: The results of occupational health monitoring of radiation workers showed that there were statistically significant differences in ALT, lens opacity (P < 0.05) and lymphocyte micronucleus (P < 0.05) between the two groups, and there were statistically significant differences in the influence of radiation service on the detection rate of lens opacity (P < 0.05). The survey results of radiation safety culture construction in medical institutions show that there are differences in the level of radiation safety culture in hospitals of different grades. The radiation safety culture construction of provincial and municipal public hospitals is obviously better than that of county hospitals, especially township hospitals.Conclusion: Interventional radiologists and nuclear medicine workers engaged in iodine therapy were exposed to higher radiation agents, and radiation workers in township health centers were not aware of radiation protection, and there was a certain occupational risk. At the same time, the evaluation index of radiation safety literacy in medical institutions was determined, Disease prevention and control personnel stationed in hospitals is an effective measure to strengthen the construction of radiation safety culture in hospitals.

Aim. To explore the role of Rac1 on sorafenib resistance in hepatocellular carcinoma. Methods. CCK-8, wound healing assay, Transwell, and cell cycle assay were used to detect the tumor cells development. Cell viability was assessed by MTT. The glycolytic pathway was revealed by cellular metabolism assays. Result. We recovered that Rac1 upregulation was related to HCC patients’ poorer prognosis. Forced expression of Rac1 promoted cell development and sorafenib chemoresistance in HCC cells. Rac1 inhibitor EHop-016 and sorafenib combination markedly prevented cell viability, G2/M phase cycle arrest, and apoptosis than single therapy. Furthermore, combination therapy decreased glycolysis in HCC cells. In vivo, the tumor growth was significantly prevented by combination therapy single therapy. Conclusion. Our research declares that Rac1 inhibition could block sorafenib resistance in HCC by decreasing glycolysis, which would provide an underlying target for HCC therapy.

Background：A biological indicator has different predictive effects on predicting different people with the same tumor. VPS72 is evolutionarily highly conserved and is capable of depositing H2A.Z in vitro experiments and the level of VPS72 expression influence the speed of this transition process. Therefore, VPS72 may be a stable predictor and therapeutic targets of liver hepatocellular carcinoma. Methods: There were 1106 patients with LIHC in study. The relational between VPS72 and H2A.Z was comprehensively investigated. The prognosis value of VPS72 was explored by by Cox regression analyses and Propensity score matching at both the mRNA and protein levels. Results：High VPS72 expression was often more correlated with high H2AFZ expression than low VPS72 expression. Indirect proof that VPS72 mRNA expression was negatively regulated by DNA methylation was according to the relationship between H2A.Z and DNA methylation. We further proved the above conclusion on real time PCR in Huh7 cell. Finally, low VPS72 mRNA expression in LIHC was associated with better OS than high VPS72 mRNA expression in four databases. At the mRNA and protein levels, low VPS72 mRNA expression in LIHC was associated with better OS (HR=8.658, P=0.024), disease-free survival (HR=4.715, P=0.007) than high VPS72 mRNA expression in LIHC by PSM, and the results showed that low VPS72 expression in our IHC data was associated with better disease-free survival (HR=4.715, P=0.007) than high VPS72 expression in our IHC data and low VPS72 expression was associated with better DFS (HR=3.14, P=0.04) than high VPS72 expression in our IHC data by PSM. Conclusions：The relational between VPS72 and H2AFZ was positive correlation and VPS72 may be a stable predictor of liver hepatocellular carcinoma.Funding: We are grateful to the financial support from the Guangdong Basic and Applied Basic Research Foundation (Grant No.2020A1515010302 and 2019A1515110654), the Fundamental Research Funds for the Central Universities(20ykpy38), China Postdoctoral Science Foundation(2019TQ0369,2020M672987) and the Special Project on National Natural Science Foundation of China (2020GZRPYMS04).Declaration of Interest: None to declare. Ethical Approval: Informed consent was obtained from each patient included in the study, This research was approved by the Human Research Ethics Committee of the three Affiliated Hospital of Sun Yat-sen University.

目的 对颈椎C2～7椎间孔外口区域的韧带进行解剖学描述并探讨其临床意义.方法 对10具成人尸体标本的100个椎间孔进行解剖观测.鉴别所有出现的韧带,观察并记录C2～7椎间孔外口区域椎间孔外韧带的数量、形态、分布和起止位置.并用游标卡尺分别测量每条韧带的长度、宽度和厚度.结果 在100个椎间孔外口区域共发现252个椎间孔外韧带.椎间孔外韧带可以分为放射型韧带236个(93.7％)和横跨型韧带16个(6.3％)两种.放射型韧带将神经根连接到周围结构,可分为上方韧带(25.0％),下方韧带(60.2％),前方韧带(6.3％)和后方韧带(8.5％);横跨型韧带与神经根相垂直并横跨于神经根上,其中,横跨型韧带在C4～5节段最为常见,在C4～5节段的平均长度为横跨型韧带长度为(8.12±1.38) mm(6.28～9.93 mm),厚度最厚可达1.04 mm,每个颈椎椎间孔最多只有一条横跨型韧带.结论 椎间孔外韧带是椎间孔正常的生理结构,可能与颈椎减压术后C5神经麻痹的发生有关.在颈椎减压术后,横跨型韧带可能是造成神经根卡压而引起神经损伤的潜在原因之一.而放射型韧带可以限制脊神经移位,可能因此牵拉神经引起损伤.

Objective:To investigate the effect of platelet-derived growth factor (PDGF) on the biomechanics of hip fracture in rats.Methods:A total of 60 SD rats were randomly divided into sham operation group, model group and experimental group by random number table method. After successfully modeling, rats in the experimental group at the fracture site were injected with adeno-associated virus overexpressing PDGF, and those in the sham operation group and the model group were injected with adeno-associated virus overexpressing empty vector. After 8 weeks of treatment, the fracture healing and bone mineral density of hip were analyzed, and the biomechanical parameters of hip were measured by three-point bending method. The mRNA expression levels of osteocalcin (OCN), bone morphogenetic protein (BMP)-2, runt related transcription factor 2 (Runx2), nuclear factor-κB receptor activator ligand (RANKL) and osteoprotegerin (OPG) at the fracture site of rats were analyzed by fluorescence quantitative polymerase chain reaction (RT-PCR). The expression of PDGF was analyzed by Western blotting.Results:The expression level of PDGF protein in experimental group (1.95±0.15) was significantly higher than that in sham operation group and model group (0.84±0.11, 0.95±0.21, t=3.901, 3.528, P<0.05). The X-ray score in the experimental group (3.10±0.35) was significantly higher than tin the model group (2.06±0.27, t=2.719, P<0.05). The BMD in the experimental group (0.212±0.007) was significantly higher than that in the model group (0.045±0.006, t=3.174, P<0.05). The maximum load, elastic load, stiffness and maximum deflection of the hip in the experimental group [(111.19±8.09) N, (81.25±6.27) N, (149.43±10.32) N/mm, (0.85±0.06) N/mm] were significantly higher than that in the model group [(63.22±7.38) N, (54.29±7.81) N, (131.39±9.32) N/mm, (0.60±0.08) N/mm, t=4.771, 4.109, 3.409, 3.004, P<0.05]. The expression of OCN, BMP-2, Runx2, RANKL and OPG of hip bone in the experimental group (1.82±0.19, 1.81±0.22, 1.75±0.16, 1.99±0.18, 2.07±0.20) was significantly higher than that in the model group (1.55±0.23, 1.31±0.25, 1.40±0.19, 1.36±0.23, 1.60±0.26, t=3.104, 3.201, 3.719, 3.281, 3.447, P<0.05). Conclusion:Adeno-associated virus mediated PDGF can significantly improve bone formation, promote the healing of hip fracture and enhance the biomechanical ability of hip.

目的 探讨应用拉杆式皮肤扩展器(skin-stretching device,SSD)治疗糖尿病足难愈性创面的临床疗效.方法 糖尿病足难愈性创面患者32例(32足),根据手术方式分为SSD组17例和植皮组15例,SSD组采用拉杆式SSD进行治疗,植皮组采用滚轴式取皮刀取皮植皮治疗.比较2组术后第1次换药视觉模拟评分(visual analogue scale,VAS),术后14、21 d创面愈合优良率,术后2个月患者对创面皮肤功能恢复的满意率.结果 SSD组患者术后第1次换药VAS评分[(4.29士0.96)分]低于植皮组[(6.42士1.04)分](P＜0.05),术后14、21 d创面愈合优良率(94.12％、94.12％)和术后2个月对创面皮肤功能恢复的满意率(82.35％)高于植皮组(73.33％、80.00％、26.67％) (P＜0.05).结论 SSD治疗糖尿病足难愈创面能减轻患者术后换药疼痛,缩短创面愈合时间,提高创面愈合质量.

MicroRNAs (miRNAs, miRs) have been found as a novel class of gene expression modulators. For patients with systemic lupus erythematosus (SLE), lupus nephritis (LN) is the predominant cause of morbidity and mortality. The NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3) is a well-known member of inflammasomes, which is an essential element in promoting inflammation and autoimmunity. By carrying out microarray analysis, we found that miR-22 was deregulated in mesangial cells of LN patients compared with normal mesangial cells (MCs). Bioinformatics study showed that NLRP3 is one of the targets of miR-22. By carrying our western blot and other assays, we found that NLRP3, ASC and active caspase1 were suppressed by miR-22. Together with the results of decreased IL-1 beta, we confirmed that miR-22 attenuated LN by downregulating the expression of NLRP3 related genes, so as the activation of NLRP3 inflammasome.

Objective To explore the application of multi-slice spiral computed tomography (MSCT) three-dimensional reconstruction in the diagnosis of ankle fractures. Methods A total of 168 cases of patients suspected as ankle fractures admitted to the hospital from February 2017 to February 2018 were analyzed retrospectively, and they were given X-ray and MSCT examination and processed by post-three-dimensional reconstruction, including multi-planar reconstruction (MPR), maximum intensity projection (MIP) and volume rendering (VR). The results of clinical operation were used as the gold standard to compare the sensitivity, specificity and accuracy of the two methods for ankle fractures.The detection of the classification of ankle fractures (supination-adduction, supinationexternal rotation, pronation-abduction, pronation-external rotation, vertical compression type) was observed between X-ray and MSCT three-dimensional reconstruction. Results The sensitivity and accuracy of MSCT scan for ankle fractures were significantly higher than those of X-ray examination [ (1.000 vs 0.933); (1.000 vs 0.935) ], and the specificity of the two was the same. There were 11 cases of missed diagnosis of ankle fractures by X-ray (3 cases of supination-adduction, 2 cases of supination-external rotation, 2 cases of pronation-abduction, 2 cases of supination-external rotation, 2 cases of vertical compression), and the detection rate of ankle fractures by MSCT examination was 100％, but 1 case was misdiagnosed (taking 1 case of pronation-abduction as supination-external rotation). Conclusion Spiral CT is more reliable in the diagnosis of ankle fractures than X-ray, and the three-dimensional reconstruction has better detection of classification of ankle fractures, and it is conducive to the development of treatment regimens for late fracture surgery.

Objective To investigate the effect of lentivirus-mediated lactoferrin transporter (LF) on the healing of osteoporotic fracture in rats.Methods Fifty SD rats were randomly divided into control group and observation group.Ovariectomy was used to establish osteoporosis model group.Lentiviruses overexpressing LF were injected into the fracture site in the observation group,and equal volume empty carrier lentivirus were injected into the fracture site in the control group.Eight weeks after injection,theexpression of LF,bone protection element (OPG) and receptor activator of nuclear factor κB ligand (RANKL) proteins was analyzed by Western blotting.Bone mineral density (BMD),trabecular volume (BV),tissue volume (TV),average trabecular thickness (Tb.Th) and average number of trabeculae (TB.N) were measured by micro-CT.Three points bending test was used to determine the biomechanical parameters of the fracture site.Results Compared to the control group (0.69 ± 0.16,0.30 ± 0.12 and 0.88 ± 0.20),the expression levels of LF,OPG and RANKL proteins in the fracture site of rats in the observation group (1.17 ±0.31,1.25 ±0.18 and 1.10 ±0.15) were significantly increased (t =2.965,2.183 and 3.018 respectively,P ＜0.01).BMD,BV,TV,Tb.Th and Tb.N in the observation group were significantly higher than those in the control group (t =4.019,3.183,2.195,3.012 and 3.091 respectively,P ＜ 0.05).The biomechanical parameters (maximum load,elastic load,stiffness and maximum deflection) of fracture site in the observation group were significantly higher than those in the control group (t=3.691,2.985,3.911 and 2.198 respectively,P＜0.01)].Conclusion Lentiviral-mediated LF expression in osteoporotic fracture can significantly promote osteoblast differentiation,promote bone growth and fracture healing,and improve bone quality.

Rosmarinic acid (RA), isolated from herbal balm mint plants, has demonstrated potent anti-tumor properties against liver cancer. However, the precise underlying mechanisms remain unclear. This study aimed to investigate the molecular mechanisms of RA in HepG2 cells. RA anti-tumor activity was assessed using 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and Hoechst 33258 staining. Apoptosis and the cell cycle distribution were evaluated by flow cytometry. A proteomics approach was used to identify differentially expressed proteins following RA treatment in HepG2 cells, and quantitative reverse transcription-quantitative polymerase chain reaction was used to validate the results. Bioinformatics analysis was also implemented to further understand the identified proteins, and western blotting was used to analyze the associated proteins. Our results suggested that RA treatment significantly inhibits the viability of HepG2 cells. The MTT and LDH assays indicated dose-dependent decreases in cell proliferation following RA treatment. Hoechst 33258 staining and flow cytometry analysis showed that RA exhibits an apoptosis-inducing effect and induces cell cycle arrest in G1. The proteomics analysis successfully identified 16 differentially expressed proteins. Bioinformatics analysis indicated that the identified proteins participated in several biological processes and exhibited various molecular functions, mainly related to inactivation of the glycolytic pathway. Further western blotting analysis showed that RA could downregulate the expression of glucose transporter-1 and hexokinase-2, leading to the suppression of glucose consumption and generation of lactate and ATP. Taken together, our study found that RA exhibits significant cytotoxic effects by inhibiting cell proliferation and inducing apoptosis and cell cycle arrest, possibly by blocking the glycolytic pathway in human HepG2 cells.

当前我国医学本科生普遍缺乏创新思维及创新实践能力,急需转变培养模式.我们尝试应用适合医学本科生的长效科研创新能力培养模式,通过兴趣激发、创新意识培养、科研创新实践和参加学术活动等方法与手段,提高医学本科生创新能力,以适应未来医疗卫生事业发展需求.

Objective To evaluate the effect of brain-derived neurotrophic factor (BDNF) combined with chondroitin ABC (chABC) on neurological function recovery and partial glial scar formation in rats with spinal cord injury (SCI).Methods Eighty SD rats were randomly divided into sham-operated group,saline treatment group,BDNF treatment group,chABC treatment group and BDNF combined with chABC treatment group (n=16);rats in the later 4 groups were established SCI rat models;immediately after SCI,10 μL saline,20 μL BDNF,6 μL chABC and 6 μL chABC+20 μL BDNF were given,and rats in the sham-operated group did not give any treatment.One,7,14 and 28 d after SCI,HE and Nissl stainings were employed to observe the glial scar formation;immunohistochemical staining was used to detect the glial fibrillary acidic protein (GFAP) expression.Results One d after SCI,HE staining and Nissl staining showed that obvious hemorrhage in the grey matter and aggregated inflammatory cells were observed in the SCI center,and Nissl substance began to break up into dust particles from speckle;7 d after SCI,Nissl substance broke up into dust particles from speckle,and died neurons,activated astrocytes and infiltrated inflammatory cells were observed;14 and 28 d after SCI,glial scars were formed,activated astrocytes were noted,Nissl substance recovered from dust particles into maculosus,and number of colored neurons increased;the recovery of Nissl substance and number of neurons in the BDNF treatment group,chABC treatment group and BDNF combined with chABC treatment group were better than those in the saline treatment group,and BDNF combined with chABC treatment group enjoyed the best recovery.One d after SCI,GFAP positive expression began in the rats of the later 4 groups,and peaked 14 d after SCI;7 d after SCI,GFAP positive labeling areas in the BDNF combined with chABC treatment group were smaller than those in the saline treatment group;14 and 28 d after SCI,GFAP positive labeling areas in the BDNF treatment group,chABC treatment group and BDNF combined with chABC treatment group were significantly smaller than those in the saline treatment group (P＜0.05);28 d after SCI,GFAP positive labeling areas in the BDNF combined with chABC treatment group were significantly smaller than those in the saline treatment group,BDNF treatment group and chABC treatment group (P＜0.05).Conclusion BDNF combined with chABC has neuroprotective and neurotrophic effects,which can reduce the proliferation of astrocytes and glial scar formation and inhibit the GFAP expression;combined effect is better than single application.

Aminophenylboronic acid (ABA) modified bovine serum albumin (BSA) was prepared as neolectin and its interactions with oligosaccharides and glycopolymer were studied by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). The conjugation between the primary amine group of the ABA molecule and lysine residues on BSA was performed with an adipate-based strategy to afford the synthetic neoprotein. The number of ABA molecules loaded to BSA surface was determined by matrix-assisted laser desorption/ionization – time of flight (MALDI-TOF) mass spectrometry. In the BSA-ABA and sugar interaction study, no signal was observed for both the SPR and ITC sensor platform using monosaccharides as the analyte, indicating a weak binding affnity, while the galactose modified polymer showed an enhanced response. The binding affinities of the galactosyl-polymer to BSA-ABA from SPR and ITC data were in the micromolar range.

Objective To investigate the effect of combined treatment of brain-derived neurotrophic factor (BDNF) with chondroitinase ABC (chABC) on repair of spinal cord injury in rats via nerve transduction pathway.Methods One hundred and fifty female SD rats were randomly divided into sham-operated group,normal saline (NS) treatment group,BDNF treatment group,chABC treatment group,and BDNF and chABC treatment group (n=30).The spinal cord injury models of rats in the later 4 groups were established successfully,and 10 μL NS,20 μL BDNF,6 μL chABC and 6 μL chABC+20 μL BDNF were given to the injury tissues 3 d after injury for a consecutive 60 d.Basso-Beattle-Bresnahan (BBB) scale was performed,and matosensory evoked potential (SEP) and motor evoked potential (MEP) were monitored;the reparation of nerve transduction pathway was observed one,7,14,28 and 60 d after spinal cord injury.Results The BBB scale scores increased accordingly in the NS treatment group,BDNF treatment group,chABC treatment group,and BDNF and chABC treatment group 28 and 60 d after injury,with significant differences between each two groups (P＜0.05).The latency of SEP N1 wave in the BDNF and chABC treatment group ([27.16±1.09] s) was significantly lower than that in the NS treatment group ([31.256±1.54] s) 14 d after injury (P＜0.05).The latency of SEP N1 wave decreased accordingly in the NS treatment group,BDNF treatment group,chABC treatment group,and BDNF and chABC treatment group 28 and 60 d after injury,with significant differences between each two groups (P＜0.05).The latency of MEP N1 wave decreased accordingly in the NS treatment group,BDNF treatment group,chABC treatment group,and BDNF and chABC treatment group 14,28 and 60 d after injury,with significant differences between each two groups (P＜ 0.05).Conclusion Combined treatment of BDNF with chABC has neurotropic and neuroprotective effects on spinal cord injury,which could help the recovery of nerve transduction pathway in rats.

近年来，我国经济发展不断加快，其中脊髓损伤(SCI)的发病率越来越高，且可能带来严重的并发症及严重症状，自主神经功能障碍是常见的并发症，现阶段还无有效的方法或特效药治疗脊髓损伤患者，治疗措施的效用也较有限，很难达到预期效果。神经功能在经历了 SCI 过后恢复的难度较大，究其根源，其中一个重要的方面就是损伤区微环境能够形成大规模的抑制因子，从而对轴突生长带来明显的抑制作用。目前，国内外学术界已经提出了多种脊髓损伤模型，如牵张损伤、化学损伤、横断损伤、缺血损伤、脊髓挫伤和压迫损伤等，从而能够充分满足各类实验的需求，然而，截止目前，还未获取一种稳定性较高的创伤性脊髓损伤模型，本文将着重介绍现阶段国内外研究现状。