Botulinum Toxin Type A and Its Possible Mechanisms on Wound Healing

Botulinum toxin type-A (BTX-A), a subtype from known seven types of botulinum neurotoxin (serotype A-G), is produced by a gram-positive bacterium, Clostridium botulinum. The toxin is now widely and efficiently used in treating a plethora of diverse symptoms and conditions. Recent evidence in the literature also shows that BTX-A exhibits a wide range of effects on non-neuronal cells. Its potential has markedly expanded to clinical applications other than the treatment of neurological and muscular conditions that are characterized by neuronal hyperactivity. A number of studies have shown BTX-A to improve the quality of scar outcome and prevent the formation of keloids and HTS. Although the mechanism of action of BTX-A on wound healing is still not clearly understood, lately there has been extensive research to grasp the underlying mechanisms of this multifunctional toxin. BTX-A seems to affect wound healing by a number of mechanisms that include action on tensile forces, inhibition of fibroblasts differentiation, downregulation of TGF-β1 and collagen expression. This review will explore the responses of Botulinum toxin type-A on wound healing and preventing pathological scars like HTS and keloids, and comprehend the overall effect BTX-A has on wound healing.

Characteristics of Anthropogenic Sulfate and Carbonaceous Aerosols over East Asia: Regional Modeling and Observation

The authors present spatial and temporal characteristics of anthropogenic sulfate and carbonaceous aerosols over East Asia using a 3-D coupled regional climate-chemistry-aerosol model, and compare the simulation with the limited aerosol observations over the region. The aerosol module consists of SO2, SO4^2-, hydrophobic and hydrophilic black carbon （BC） and organic carbon compounds （OC）, including emission, advections, dry and wet deposition, and chemical production and conversion. The simulated patterns of SO2 are closely tied to its emission rate, with sharp gradients between the highly polluted regions and more rural areas. Chemical conversion （especially in the aqueous phase） and dry deposition remove 60% and 30% of the total SO2 emission, respectively. The SO4^2- shows less horizontal gradient and seasonality than SO2, with wet deposition （60%） and export （27%） being two major sinks. Carbonaceous aerosols are spatially smoother than sulfur species. The aging process transforms more than 80% of hydrophobic BC and OC to hydrophilic components, which are removed by wet deposition （60%） and export （30%）. The simulated spatial and seasonal SO4^2-, BC and OC aerosol concentrations and total aerosol optical depth are generally consistent with the observations in rural areas over East Asia, with lower bias in simulated OC aerosols, likely due to the underestimation of anthropogenic OC emissions and missing treatment of secondary organic carbon. The results suggest that our model is a useful tool for characterizing the anthropogenic aerosol cycle and for assessing its potential climatic and environmental effects in future studies.

TIR/BB-loop mimetic AS-1 protects vascular endothelial cells from injury induced by hypoxia/reoxygenation

Morphological and functional abnormalities of vascular endothelial cells(VECs) are risk factors of ischemiareperfusion in skin flaps.Signaling pathway mediated by interleukin-1 receptor(IL-1 R) is essential to hypoxia/reoxygenation(H/R) injury of VECs.While the TIR/BB-loop mimetic(AS-1) disrupts the interaction between IL-1 R and myeloid differentiation primary-response protein 88(MyD88),its role in the VECs dysfunction under H/R is unclear.In this study,we first showed that there was an infiltration of inflammatory cells and the apoptosis of VECs by using a skin flap section from patients who received flap transplantation.We then showed that the H/R treatment induced apoptosis and loss of cell migration of endothelial cell line H926 were attenuated by AS-1.Furthermore,our data suggested that AS-1 inhibits the interaction between IL-1 R and MyD88,and subsequent phosphorylation of IκB and p38 pathway,as well as the nuclear localization of NF-κB subunit p65/p50.Thus,this study indicated that the protective role of AS-1 in H/R induced cellular injury may be due to the AS-1 mediated down-regulation of IL-1 R signaling pathway.

Long-term medical treatment of patients with severe burns at exposed sites

BACKGROUND Body parts such as the face and hands are highly exposed during daily life and burns may accumulate in these areas.In addition,residual wounds,scar hyperplasia and contracture often exist in the late stage of a deep burn in these areas,which may affect patients’appearance,movements,and mental health.However,inadequate attention has been paid to this issue which can result in problems,such as difficulty in healing,possibility of carcinoma,chronic pain and a heavy mental burden.AIM To investigate the long-term medical treatment of patients with severe burns at exposed sites following a mass burn casualty event.METHODS A retrospective analysis of 13 patients with severe burns at exposed sites was performed to determine their respective long-term medical treatment.A combined wound dressing scheme consisting of traditional Chinese and Western medicine was introduced to repair residual wounds.Active and passive functional exercises with massage,Chinese herbal baths and compression fixation were proposed to ameliorate the condition of the hands.A combination of physical,chemical and photoelectrical measures was adopted for anti-scar treatment.A psychological intervention and recovery guide was provided which corresponded to the patients’psychological status.RESULTS Compared to patients who did not simultaneously receive the same treatment,patients who underwent systematic treatment recovered with a lower woundinfection rate(P<0.05),a shorter healing time(13.6±3.2 d)compared with(19.1±3.5 d)and more bearable pain during wound dressing at three days,one week and two weeks after a Chinese herbal bath(P<0.05).Satisfactory results were achieved with regard to restored function of patients’joints and blood supply to nerve endings,closure of the eyelids and the size of mouth opening tended to be normal,and only 7.1%of patients were diagnosed with severe scar hyperplasia and contracture deformity compared with 30.7%in the control group.In addition,the color,thickness,vascular distribution and softness score of the scars improved(P<0.01),and the effects of the psychological intervention was remarkable as shown by the Self-Rating Anxiety Scale and Self-Rating Depression Scale.CONCLUSION A better prognosis can be achieved in patients in the late stage of a burn with active residual wound repair,limb functional exercise,anti-scar and psychological rehabilitation.

Deep Learning-Based Automatic Detection and Evaluation on Concrete Surface Bugholes

Concrete exterior quality is one of the important metrics in evaluating construction project quality.Among the defects affecting concrete exterior quality,bughole is one of the most common imperfections,thus detecting concrete bughole accurately is significant for improving concrete exterior quality and consequently the quality of the whole project.This paper presents a deep learning-based method for detecting concrete surface bugholes in a more objective and automatic way.The bugholes are identified in concrete surface images by Mask R-CNN.An evaluation metric is developed to indicate the scale of concrete bughole.The proposed approach can detect bugholes in an instance level automatically and output the mask of each bughole,based on which the bughole area ratio is automatically calculated and the quality grade of the concrete surfaces is assessed.For demonstration,a total of 273 raw concrete surface images taken by mobile phone cameras are collected as a dataset.The test results show that the average precision(AP)of bughole masks is 90.8%.

Proportion and characteristic of emmetropia in schoolchildren aged 6-11y:the Shenzhen elementary school eye study

AIM:To investigate the proportion and characteristic of emmetropia in schoolchildren aged 6-11,especially estimate the normal value of ocular biometric parameters of emmetropia.METHODS:A population-based cross-sectional study was conducted on children aged 6-11 y in Shenzhen.Totally,2386 schoolchildren from two primary schools were involved.The axial length(AL)and the corneal radius of curvature(CRC)were measured by partial coherence laser interferometry.Noncycloplegic refraction and refractive astigmatism(RA)was measured using autorefraction.The axial length-to-corneal radius of curvature ratio(AL/CRC),corneal astigmatism(CA)and spherical equivalent refraction(SER)were calculated.RESULTS:The proportion of emmetropia in elementary school students was 41.30%.This percentage decreased gradually from 6 to 11 years of age and decreased rapidly after 9 years of age.The mean and 95%CI of each parameter were provided for boys and girls aged 6 to 11 years of age with emmetropia according to each age group.The change trend of parameters of boys and girls are similar.After 7 years of age,the AL of non-emmetropia started to increase faster than that of emmetropia.The change trend of AL/CRC was the same as that of AL.The other parameters tend to be stable after 7 years of age.CONCLUSION:The age of 7-9 is an important period for the changes of refractive state and ocular biometric parameters of primary school students,and it is a special focus period for children myopia prevention.The normal value and variation of ocular biometric parameters of emmetropia can provide the basis for the clinical judgment of whether or not children’s ocular biometric parameters obtained by single measurement and changes obtained by multiple measurements are abnormal.

Therapeutic effect analysis on the treatment of congenital glaucoma through modified combined trabeculotomy-trabeculectomy

AIM： To evaluate the therapeutic effect and the safety of the treatment of congenital glaucoma through modified combined trabeculotomy-trabeculectomy. METHODS： The clinical data of 27 cases （altogether 42 eyes）, which included 7 cases of infants （10 eyes） and 20 cases of teenagers （32 eyes）, of congenital glaucoma undertook modified combined trabeculotomy trabeculectomy were analyzed retrospectively. The parameters evaluated included the post operation visual acuity, the anterior chamber, the filtering bleb, the intraocular pressure, the C/D ratio, visual field, the retinal nerve fiber layer changes and the complications. RESULTS： The follow-up period was 1 to 29mo, averaging 13.3 ±7.7mo. Upon the last visit after the operation, functional filtering blebs developed in all the involved eyes. The intraocular pressure was controlled under 21 mm Hg, which was decreased by 60% when compared with that before the operation, without using any medication. There were no significant changes in the post operation visual acuity and the retinal nerve fiber layer thickness before and after the operation in teenager group （P〉0.05）, and both the post operation C/D ratio and the visual field mean defect （MD） were reduced compared with those before the operation （P〈0.05）. There were no severe complications in any of the patients. CONCLUSION： The modified combined trabeculotomy- trabeculectomy can effectively reduce the intraocular pressure and control the development of glaucoma in cases of congenital glaucoma. It is a safe and effective operative method for the treatment of congenital glaucoma

Research and perspectives on criteria for evaluation of nursing research achievements

This paper introduces concepts related to scientific research achievements, analyzes current evaluation methods with regard to nursing research achievements and their application at home and abroad, and summarizes findings from the investigation of obstacles to the application of nursing research results in China, aiming to provide reference points for the evaluation and application of nursing research results in China.

Anti-fatigue Effect of L-arginine Complex Preparation on Mice

Objective:To investigate the anti-fatigue effect of L-arginine complex preparation on mice.Methods:The experimental mice were divided into a blank group,low dose group,medium dose group and high dose group.L-arginine complex preparation mice were intragastrically administered for 30 days,and the mice were tested for exhaustive swimming time.At the same time,contents of plasma lactic acid,lactate dehydrogenase,urea nitrogen and hepatic glycogen were measured.Results:Compared with the blank control group,the weight-bearing swimming time and hypoxia-tolerant survival time of the low,middle and high dose groups was significantly increased(P<0.05).Whereas,the serum urea nitrogen levels and lactose content were significantly decreased(P<0.05).However,compared with the blank control group,the liver glycogen content of the middle and high dose groups was increased significantly(P<0.05),and there was no significant difference in the low dose group.Conclusion:The L-arginine complex preparation has an anti-fatigue function in mice.

Stem cell niche-inspired microcarriers with ADSCs encapsulation for diabetic wound treatment

Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades,while their short in vivo residence,alloimmune reactions,undesired behaviors,and dramatic losses of cell functions still hinder the translation of them into clinic.Here,inspired by the natural components of stem cell niches,we presented novel microfluidic hydrogel microcarriers with extracellular matrix(ECM)-like composition and adipose-derived stem cells(ADSCs)encapsulation for diabetic wound healing.As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl(HAMA)onto the Fibronectin(FN)molecule chain(FN-HAMA),the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities.Based on these features,we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization,follicular rejuvenation,and collagen deposition in a mouse diabetic wound model.These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.

Engineered artificial skins:Current construction strategies and applications

Skin damage resulting from burns,injuries,or diseases can lead to significant functional and esthetic deficits.However,traditional treatments,such as skin grafting,have limitations including limited donor skin availability,poor aesthetics,and functional impairment.Skin tissue engineering provides a promising alternative,with engineered artificial skins offering a highly viable avenue.Engineered artificial skin is designed to mimic or replace the functions of natural human skin and find applications in various medical treatments,particularly for severe burns,chronic wounds,and other skin injuries or defects.These artificial skins aim to promote wound healing,provide temporary coverage,permanent skin replacement,and restore the skin’s barrier function.Artificial skins have diverse applications in medicine and wound care,addressing burns,chronic wounds,and traumatic injuries.They also serve as valuable tools for research in tissue engineering,offering experimental models for studying wound healing mechanisms,testing new biomaterials,and exploring innovative approaches to skin regeneration.This review provides an overview of current construction strategies for engineered artificial skin,including cell sources,biomaterials,and construction techniques.It further explores the primary application areas and future prospects of artificial skin,highlighting their potential to revolutionize skin reconstruction and advance the field of regenerative medicine.

Chronic wounds:pathological characteristics and their stem cell-based therapies

Chronic wounds are characterized by prolonged healing processes and poor prognoses,which have substantially impacted human health and daily life.Traditional treatment strategies have various limitations and drawbacks.Therefore,fully effective therapeutic approaches remain urgently needed.Stem cell(SC)-based therapies have drawn significant attention for their abilities of immunomodulation and pro-regeneration.It has been demon-strated that stem cells(SCs)can improve angiogenesis,collagen deposition,and hair rejuvenation,thus facilitating wound healing.In addition,attempts were performed to facilitate the cell survival,function,retention,and en-graftment of the delivered SCs.In this review,we first introduce the pathological process involved in chronic wound healing.Following that,the mechanism of SCs in promoting chronic wound repair is discussed in detail.Then,we highlight recent SC-based therapies for chronic wound repair developments.Finally,we present our views on the remaining challenges and future trends of SC-based therapies for chronic wound treatment.

双眼三焦点人工晶状体和双焦点人工晶状体植入术后早期视觉质量比较

目的:对双眼植入三焦点人工晶状体(IOL)或双焦点IOL术后早期的视觉质量进行比较研究。方法:前瞻性临床研究。选择武汉爱尔眼科医院2017年4月至2018年5月收治的双眼单纯年龄相关性白内障患者52例(104眼),依据患者选择的IOL进行分组,双眼均植入双焦点IOL26例(52眼)作为双焦点组,双眼均植入三焦点IOL26例(52眼)患者作为三焦点组,术后随访3个月,观察2组间裸眼远视力(UDVA)、裸眼中视力(UIVA)、裸眼近视力(UNVA)、矫正远视力(BCDVA)、矫正远中视力(DCIVA)、矫正远近视力(DCNVA)、离焦曲线、对比敏感度、波前像差、调制传递函数等,并进行VF-14-CN生活质量问卷满意度及脱镜率调查。数据采用独立样本t检验、Mann-WhitneyU检验及χ^2检验进行统计分析。结果:三焦点组UIVA明显优于双焦点组(Z=-2.347,P=0.019),而2组间UDVA、UNVA、BCDVA、DCIVA、DCNVA差异均无统计学意义。三焦点组在-1.0、-3.0、-3.5、-4.0D离焦下视力明显优于双焦点组(Z=-2.619、-2.452、-2.452、-2.147,P=0.009、0.014、0.014、0.032)。2组间明视及明视眩光对比敏感度差异均无统计学意义。3、5mm瞳孔直径时,三焦点组眼内总高阶像差、眼内彗差、眼内三叶草差以及全眼总高阶像差、全眼三叶草差均明显低于双焦点组,差异均有统计学意义(P<0.05)。5mm瞳孔直径时,三焦点组眼内球差明显低于双焦点组(Z=-3.053,P=0.002),余指标组间差异无统计学意义。2组在3、5mm瞳孔直径时的调制传递函数差异均无统计学意义。2组间VF-14-CN得分、日常生活脱镜率以及患者满意度差异均无统计学意义。结论:与双眼植入双焦点IOL相比,双眼植入三焦点IOL能够为患者带来更好的中间距离视力,但二者在远近视力、视觉质量以及术后生活质量方面相近。

六种人工晶状体计算公式预测三焦点人工晶状体屈光度准确性的比较

目的:评估Barrett Universal Ⅱ计算公式预测三焦点人工晶状体(IOL,AT Lisa tri.839MP)屈光度的准确性,并与其他5种IOL计算公式(Haigis、Hoffer Q、SRK/T、SRK II和HolladayⅠ)进行对比。方法:前瞻性临床研究。选择2016年12月至2018年8月于武汉爱尔眼科医院行飞秒激光辅助超声乳化白内障吸除联合三焦点IOL植入术的患者。术前使用Lenstar LS 900进行光学生物测量,并通过该仪器内置的其中6种IOL计算公式预测术后屈光度,IOL优化常数取自ULIB网站。随访至术后3个月行主觉验光,比较各IOL计算公式平均绝对屈光误差(MAE)的差异,并对各公式绝对屈光误差中值(MedAE)、绝对屈光误差最大值(MaxAE)以及术后屈光误差在±0.5 D、±1.0 D和±2.0 D范围内患眼的百分比进行评估比较。数据采用Kruskal-Wallis H检验进行分析。结果:本研究最终纳入患者55例(78眼)。根据各公式MAE值由小到大排序,依次为Barrett universal Ⅱ(0.332 D)、SRK/T(0.420 D)、Haigis(0.480 D)、HolladayⅠ(0.607 D),Hoffer Q(0.626 D)以及SRK Ⅱ(0.822 D)。各公式MAE差异有统计学意义(P<0.001)。Barrett Universal Ⅱ公式中MaxAE小于其他IOL计算公式。术后屈光误差在±0.5 D、±1.0 D以及±2.0 D范围内患眼所占百分比,Barrett Universal Ⅱ公式最高,分别为73%、95%以及100%。结论:Barrett Universal Ⅱ、SRK/T、Haigis公式能相对更准确地预测患者术后实际屈光结果。对于植入三焦点IOL的患者我们推荐使用Barrett Universal Ⅱ、SRK/T或者Haigis公式。

Relationship between postoperative complications and fibular integrity in congenital pseudarthrosis of the tibia in children

Background:This study aimed to investigate the relationship between postoperative complications and fibular integrity in congenital pseudarthrosis of the tibia (CPT) in children.Methods:A retrospective study was performed in 59 patients with Crawford type Ⅳ CPT who were treated with combined surgical technique from 2007 to 2011.The patients were divided into two groups,the CPT with fibular pseudarthrosis (group A) and CPT with intact fibula groups (group B),on the basis of fibula status after the union of CPT.The incidence rates of refracture,ankle vaigus,tibial valgus,and limb length discrepancy in the two groups were investigated.Results:In group A,14 (36.8%) cases had refracture,30 (78.9%) had ankle valgus;27 (71%) exhibited tibial valgus with an average tibial valgus of 7 (6-20),and 24 (63.2%) had limb length discrepancy with an average limb length of 1.26 cm (0.6-4.4 cm).In group B,2 (9.5%) cases had refracture,11 (52.4%) had ankle valgns,8 (42.9%) had tibial valgus with an average tibial valgus deformity of 2.9 (6-13),and 13 (61.9%) had limb length discrepancy with an average limb length of 1.48 cm (0.5-5 cm).Significant difference in refracture and ankle valgus was found between groups A and B (P<0.05).Conclusions:After the union of CPT,patients with fibular pseudarthrosis showed higher incidence of refracture and ankle valgus than those with intact fibula.Attention should be paid to the presence of fibular pseudarthrosis when managing CPT.

Challenges and innovations in treating chronic and acute wound infections:from basic science to clinical practice

Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality.The underlying mechanism of infections has been widely investigated by scientist,while standard wound management is routinely been used in general practice.However,strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization,delayed healing and drug resistance.In the present review,we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis,non-surgical methods and surgical methods.Moreover,we highlight emerging innovations in the development of antimicrobial peptides,phages,controlled drug delivery,wound dressing materials and herbal medicine,and find that sensitive diagnostics,combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.

Coupled planning of water resources and agricultural land-use based on an inexact-stochastic programming model

Water resources are fundamental for support of regional development. Effective planning can facilitate sustainable management of water resources to balance socioeconomic development and water conservation. In this research, coupled planning of water resources and agricultural land use was undertaken through the develop- ment of an inexact-stochastic programming approach. Such an inexact modeling approach was the integration of interval linear programming and chance-constraint pro- gramming methods. It was employed to successfully tackle uncertainty in the form of interval numbers and probabil- istic distributions existing in water resource systems. Then it was applied to a typical regional water resource system for demonstrating its applicability and validity through generating efficient system solutions. Based on the process of modeling formulation and result analysis, the developed model could be used for helping identify optimal water resource utilization patterns and the corresponding agri- cultural land-use schemes in more, a number of decision three sub-regions. Further- alternatives were generated under multiple water-supply conditions, which could help decision makers identify desired management policies.

Puerarin improves diabetic wound healing via regulation of macrophage M2 polarization phenotype

Background:Skin wound healing depends on the progress of different but overlapping stages of healing,including hemostasis,inflammatory,proliferative and remodeling.Failure of these stages to occur in a timely and gradual manner may result in non-healing pathological wounds.Macrophages and neutrophils have been shown to play an essential role in the inflammatory responses of wound tissue,and their active plasticity allows them to modulate tissue damage and repair functions.The ability of macrophages and neutrophils to regulate the occurrence and resolution of inflammatory processes is essential for the treatment of pathological wound healing.Methods:Mice were categorized into negative control,streptozotocin,streptozotocin+puerarin and puerarin groups.The traditional Chinese medicine extract puerarin was selected to treat different groups of mice with a full-thickness skin defect wound.Cells of the RAW264.7 cell line were stimulated under different puerarin conditions.Then,real time quantitative polymerase chain reaction(RT-qPCR),western blot,immunofluorescence and other assays were carried out to explore the effect of puerarin on wound healing and its molecular mechanism.Results:Animal experiments found that the wound healing of diabetic mice treated with puerarin was significantly accelerated,and histological analysis found that puerarin treatment markedly decreased the infiltration of macrophages and neutrophils in wound tissue.Through western blot,RT-qPCR and immunofluorescence experiments,it was observed that puerarin treatment remarkably inhibited nuclear factor kinase B(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathways,downregulated the expression of inflammatory cytokines and induced the M2 polarization of macrophages.At the cellular level,we also observed that puerarin improved M2 macrophage polarization and inhibited inflammatory pathway activation in a high-glucose culture.Conclusion:Puerarin has a significant therapeutic effect on wound healing in diabetic mice.The therapeutic effect is achieved by regulating macrophage polarization through suppressing NF-κB and MAPK signaling cascades.

Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1H-pyrazol-4-yl) amino) quinazolin-6-yl)-N-(3-(trifluoromethyl) phenyl) benzamides as potent discoidin domain receptor inhibitors for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic fatal lung disease with a median survival time of 3–5 years.Inaccurate diagnosis,limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need.In recent years,it was reported that DDRs are potential targets in anti-fibrosis treatment.Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases,such as RET,AXL and ALK.Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities,low toxicity,good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy.Therefore,we confirmed that discoidin domain receptors are promising drug targets for IPF,and compound 47 would be a promising candidate for further drug development.