Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retin...Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.展开更多
Objectives:This study aimed to explore the voices of Indonesian migrant nurses on their retention in Japanese healthcare facilities.Methods:A descriptive qualitative study was conducted between June and September 2023...Objectives:This study aimed to explore the voices of Indonesian migrant nurses on their retention in Japanese healthcare facilities.Methods:A descriptive qualitative study was conducted between June and September 2023.The snowball sampling method was utilized to recruit 22 Indonesian nurses working in healthcare facilities in seven prefectures of Japan.Semi-structured interviews were conducted based on their shared experiences.All interview data were audio-recorded,transcribed verbatim,and analyzed using thematic analysis.Results:Six prominent themes and 15 subthemes emerged:1)organizational factors(caring leader,involvement in decision making,career development,and participation in training);2)social support systems(group support,colleagues support and friend support);3)individual drive(lifelong learning and persistent);4)national policies(government support in public service and flexibility in finding a comfortable placement);5)family factors(positive support of child education and development and maintaining relationship with spouse);and 6)economic factors(staying due to high salary and increasing income streams).Conclusions:Retention of Indonesian migrant nurses in Japan is a multifaceted challenge that hinges on various interconnected factors.This study has gone some way toward enhancing our understanding of international nurse retention in the receiving countries.Corresponding supports at the individual,family,organizational,economic,social,and national policy levels should be considered to keep them in their destination countries.展开更多
BACKGROUND Ki-67 is a routine test item in clinical pathology departments.However,its prognostic value requires further investigation,especially in the context of research using machine learning(ML),which remains rela...BACKGROUND Ki-67 is a routine test item in clinical pathology departments.However,its prognostic value requires further investigation,especially in the context of research using machine learning(ML),which remains relatively underdeveloped.AIM To investigate the prognostic value of Ki-67 in cases of colorectal carcinoma(CRC)and explore the potential application of ML algorithms to predict the Ki-67 index.METHODS Case data and pathological sections from two centers were systematically collected.To analyze the prognostic value of the Ki-67 index in CRC,multiple cutoff values were established.Meanwhile,by virtue of the histological features presented in the hematoxylin and eosin-stained CRC images,three mainstream ML algorithms,support vector machine(SVM),random forest(RF),and eXtreme gradient boosting(XGBoost)were employed to construct prediction models.Subsequently,the potential of these algorithms to classify and predict the Ki-67 index was explored.RESULTS Non-parametric tests revealed that Ki-67≥40%correlated with a high histological grade(P=0.017),deficient mismatch repair protein status associated with≥50%-90%cutoffs(all P≤0.028),and≥80%linked to lymph node metastasis(P=0.006).Kaplan-Meier analysis showed that Ki-67≥50%predicted higher survival(log-rank P=0.0299,hazard ratio=2.142),with no differences for other cutoffs.COX regression identified the Ki-67 positive rate as a significant predictor(P=0.027,hazard ratio=2.583),while other variables had no association.In algorithmic model predictions,the SVM,RF,and XGBoost models achieved training area under the curve(AUC)values of 0.851,0.948,and 0.872,respectively,with corresponding test set AUC values of 0.795,0.755,and 0.750,respectively.During external validation,their AUC values for predicting Ki-67 status reached 0.757,0.749,and 0.783,respectively.CONCLUSION In algorithmic model predictions,the SVM,RF,and XGBoost models achieved training AUC values of 0.851,0.948,and 0.872,respectively,with corresponding test set AUC values of 0.795,0.755,and 0.750,respectively.During external validation,their AUC values for predicting Ki-67 status reached 0.757,0.749,and 0.783,respectively.展开更多
Endothelial keratoplasty(EK)is defined as an umbrella term comprising methods for selective surgical replacement of corneal endothelium and adjacent corneal tissue,which retains healthy portions of a patient's cor...Endothelial keratoplasty(EK)is defined as an umbrella term comprising methods for selective surgical replacement of corneal endothelium and adjacent corneal tissue,which retains healthy portions of a patient's cornea while replacing diseased innermost corneal layer(s)with healthy donor tissue,to achieve corneal dehydration and transparency before the onset of irreversible stromal edema and permanent loss of corneal clarity.Recently,the pathophysiology of corneal decompensation is increasingly being researched upon.Consequent improvement in pharmacotherapy is progressively leading to reduction in the indications of EK.In addition,EK techniques have progressed towards using thinner tissue,optimizing visual outcomes.Improvements have enabled better donor tissue formulation,usage,and attachment,and surgical modifications have enhanced the tissue utilization in difficult clinical scenarios lowering failure and rejection.However,challenges are encountered in various complex clinical scenarios in-cluding eyes with prior intraocular surgery,complex anterior chamber anatomy,glaucoma,ocular surface disease etc.These complexities demand tailored surgical strategies,including modifications in graft handling,instru-mentation,and postoperative management to ensure success.Attention to these details and addressing patient-specific factors can help improve outcomes in these difficult cases.The choice of procedure depends on multiple factors,including the surgeon's experience,patient's ocular anatomy,and the specific clinical scenario.This review article encompasses the recent developments in this field presenting a comprehensive picture of our modern understanding of the indications,contraindications,surgical techniques,clinical situations,community aspects and future directions pertaining to EK.展开更多
Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from dam...Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.展开更多
OBJECTIVE:To test the hypothesis that moxibustion may inhibit rheumatoid arthritis(RA)synovial inflammation by regulating the expression of macrophage migration inhibitory factor(MIF)/glucocorticoids(GCs).METHODS:Fift...OBJECTIVE:To test the hypothesis that moxibustion may inhibit rheumatoid arthritis(RA)synovial inflammation by regulating the expression of macrophage migration inhibitory factor(MIF)/glucocorticoids(GCs).METHODS:Fifty male Sprague-Dawley rats were randomly divided into five groups(n=10 each):blank Control(CON)group,RA Model(RA)group,Moxibustion(MOX)group,MIF inhibitor(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester(ISO-1)group,and Moxibustion+MIF inhibitor ISO-1(MOX+ISO-1)group.Rats in the ISO-1 group and ISO-1+MOX group were intraperitoneally injected with the inhibitor ISO-1.The rats in the RA group,ISO-1 group,MOX group,and ISO-1+MOX group were injected with Freund's complete adjuvant(FCA)in the right hind footpad to establish an experimental RA rat model.In the MOX group and MOX+ISO-1 group,rats were treated with Moxa.The thickness of the footpads of the rats in each group was measured at three-time points before,after modeling and after moxibustion treatment.The contents of serum MIF,corticosterone(CORT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by enzyme-linked immunosorbent assay;and the contents of synovial MIF were detected by Western blot.Hematoxylin-eosin(HE)staining method was used to observe the pathological changes of synovial tissue under a section light microscope,and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease.RESULTS:Moxibustion was found to reduce the level of MIF and alleviate inflammation in RA rats in this study.In addition,after inhibiting the expression of MIF,the level of CORT increased,and the level of TNF-α decreased.Treating RA rats with inhibited MIF by moxibustion,the level of CORT was almost unchanged,but the level of TNF-α further decreased.The correlation analysis data suggested that MIF was positively related to the expression of TNF-α and negatively correlated with the expression of CORT.CONCLUSION:Reducing MIF to increase CORT and decrease TNF-α by moxibustion treatment in RA.MIF may be a factor for moxibustion to regulate the expression of CORT,but the expression of TNF-α is due to the incomplete regulation of the MIF.This study added to the body of evidence pointing to moxibustion's antiinflammatory mechanism in the treatment of RA.展开更多
OBJECTIVE:To determine whether moxibustion had an anti-inflammatory effect on rheumatoid arthritis(RA)by regulating Annexin 1 expression and interfering with the phospholipaseA2 signaling pathway.METHODS:Thirty male S...OBJECTIVE:To determine whether moxibustion had an anti-inflammatory effect on rheumatoid arthritis(RA)by regulating Annexin 1 expression and interfering with the phospholipaseA2 signaling pathway.METHODS:Thirty male Sprague-Dawley rats were randomly categorized into five groups(six rats per group):blank control(CON)group,RA model(RA)group,moxibustion(MOX)group,Annexin 1 lentiviral intervention(RNAi-Anxa1)group,and Annexin 1 lentiviral intervention+moxibustion(RNAi-Anxa1+MOX)group.The rats in the RNAi-Anxa1 and the RNAi-Anxa1+MOX groups were injected with the lentiviral vector-mediated RNAi-Anxa1 into the rat foot pad.An experimental RA rat model was established by injecting Freund's complete adjuvant(FCA)into the RA,MOX,RNAi-Anxa1,and RNAi-Anxa1+MOX groups.Rats in the MOX and RNAiAnxa1+MOX groups received moxibustion treatment.After modeling,using moxibustion“Shenshu(BL23)”and“Zusanli(ST36)”,each point is 5 times,bilateral alternating,once a day,6 times for a course of treatment,between the courses of rest for a one day.A total of three treatment courses were conducted.Both bilateral pad thicknesses were measured using Vernier calipers on experimental days 1,7,14,21,and 28.The expression of cPLA2αsignaling in the synovium of diseased joints was observed using Western blot.The pathology of the rat ankle synovium was observed using hematoxylineosin(HE)staining.Interleukin(IL)-1β,IL-10,prostaglandin E2(PGE2),and leukotriene B4(LTB4)were detected using enzyme-linked immunosorbent assay.RESULTS:Moxibustion increased the levels of Annexin 1 and decreased the inflammatory response in rats with RA.After increasing the expression of Annexin 1,the phosphorylated expression of cPLA2αwas inhibited,the serum levels of IL-1β,PGE2,and LTB4 decreased,and the level of IL-10 increased.In moxibustion treated RA rats after the Annexin 1 lentiviral intervention,the serum levels of IL-1β,PGE2,LTB4,and IL-10 were almost unchanged.CONCLUSION:Moxibustion enhanced the negative regulation of the cPLA2αsignaling pathway,increased the synovial Annexin 1 expression,inhibited the cPLA2αsignaling pathway,indirectly inhibited the expression of downstream inflammatory factors,and played a role in reducing inflammation.展开更多
Despite the profound cultural and medicinal heritage of traditional African medicines (TAM), their global recognition remains notably limited. This study investigates the factors behind this issue, focusing on cultura...Despite the profound cultural and medicinal heritage of traditional African medicines (TAM), their global recognition remains notably limited. This study investigates the factors behind this issue, focusing on cultural perceptions, scientific validation, regulatory frameworks, and pharmaceutical industry influence. Utilizing a systematic literature review (SLR) to provide a thorough and structured overview, the research addresses these factors with transparency and reproducibility. Key findings reveal that negative cultural perceptions, the dominance of Western medicine, and skepticism towards traditional healers, especially in urban and educated populations, marginalize TAM. Additionally, religious beliefs and historical influences, such as colonialism, further devalue indigenous knowledge systems. The study also highlights a significant lack of scientific research and clinical trials, which challenges the conventional validation of TAM’s efficacy. Moreover, inconsistent international and national regulatory frameworks and the pharmaceutical industry’s dominance impede TAM’s integration into global healthcare systems. To enhance TAM’s credibility and global acceptance, the study advocates for standardized regulatory policies, increased scientific research, and a reevaluation of intellectual property laws. This shift towards a more inclusive and integrative approach in global health systems could bridge the gap between traditional and modern medical practices, promoting a more holistic understanding of health and wellness.展开更多
This paper shows a didactic model (PGM), and not only, but representative of the Hadrons described in the Standard Model (SM). In this model, particles are represented by structures corresponding to geometric shapes o...This paper shows a didactic model (PGM), and not only, but representative of the Hadrons described in the Standard Model (SM). In this model, particles are represented by structures corresponding to geometric shapes of coupled quantum oscillators (IQuO). By the properties of IQuO one can define the electric charge and that of color of quarks. Showing the “aurea” (golden) triangular shape of all quarks, we manage to represent the geometric combinations of the nucleons, light mesons, and K-mesons. By the geometric shape of W-bosons, we represent the weak decay of pions and charged Kaons and neutral, highlighting in geometric terms the possibilities of decay in two and three pions of neutral Kaon and the transition to anti-Kaon. In conclusion, from this didactic representation, an in-depth and exhaustive phenomenology of hadrons emerges, which even manages to resolve some problematic aspects of the SM.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular diseases independently of other risk factors.However,data on its effect on cardiovascular outcomes in coronavirus disease 2019(CO...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular diseases independently of other risk factors.However,data on its effect on cardiovascular outcomes in coronavirus disease 2019(COVID-19)hospitalizations with varied obesity levels is scarce.Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.AIM To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity.METHODS COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease-10 CM codes in the 2020 National Inpatient Sample database.Overweight and Obesity Classes Ⅰ,Ⅱ,and Ⅲ(body mass index 30-40)were compared.Major adverse cardiac and cerebrovascular events(MACCE)(all-cause mortality,acute myocardial infarction,cardiac arrest,and stroke)were compared between groups.Multivariable regression analyses adjusted for sociodemographic,hospitalization features,and comorbidities.RESULTS Our analysis comprised 13260 hospitalizations,7.3% of which were overweight,24.3% Class Ⅰ,24.1% Class Ⅱ,and 44.3% Class Ⅲ.Class Ⅲ obesity includes younger patients,blacks,females,diabetics,and hypertensive patients.On multivariable logistic analysis,Class Ⅲ obese patients had higher risks of MACCE,inpatient mortality,and respiratory failure than Class Ⅰ obese patients.Class Ⅱ obesity showed increased risks of MACCE,inpatient mortality,and respiratory failure than Class I,but not significantly.All obesity classes had non-significant risks of MACCE,inpatient mortality,and respiratory failure compared to the overweight group.CONCLUSION Class Ⅲ obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class Ⅰ.Using the overweight group as the reference,unfavorable outcomes were not significantly different.Morbid obesity had a greater risk of MACCE regardless of the referent group(overweight or Class Ⅰ obese)compared to overweight NAFLD patients admitted with COVID-19.展开更多
The anthocyanin pigment extracted from green-wheat-bran was studied to identify its antioxidant activity.The antioxidant activities of the pigment were evaluated by anti-lipid peroxidation,total antioxidant activity ...The anthocyanin pigment extracted from green-wheat-bran was studied to identify its antioxidant activity.The antioxidant activities of the pigment were evaluated by anti-lipid peroxidation,total antioxidant activity （TAA）,superoxide anion radical scavenging activity （SARSA）,active oxygen scavenging activity （AOSA）,and DPPH （1,1-diphenyl-2 picrylhydrazyl free radical） radical scavenging activity.The results showed that the pigment had higher antioxidant activity and TAA,SARSA,AOSA and DPPH.scavenging activities at a certain concentration than Vc （antiscorbutic vitamin,vitamin C）,and the capacity increased with the increase of pigment concentration.Its TAA was 51.06 U mL-1,1.73 times of Vc,and SARSA 18 025.21 U mL-1,2.26% higher than Vc,and AOSA 3 776.31 U mL-1,1.24 times of Vc.As to the DPPH.scavenging activity of the pigment,there was a trend that higher concentration performed higher activity significantly improved with the company of Vc.The pigment showed significant antioxidant activities evaluated by different assays.Results will provide a better understanding on antioxidant activity of green wheat and allow the screening or breeding of green wheat varieties with higher antioxidant activity for food processing.展开更多
Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising al...Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy.Following laser refractive surgery,the corneal nerves,epithelial and stromal cells release neuromediators,including neurotrophins,neuropeptides and neurotransmitters.Notably,nerve growth factor,substance P,calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration.Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced.In this review,we will discuss the(1)Functions of neuromediators and their physiological and clinical significance;(2)Changes in the neuromediators following various laser refractive surgeries;(3)Correlation between neuromediators,ocular surface health and corneal nerve status;and(4)Future directions,including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery,and as adjuncts to aid in corneal regeneration after laser refractive surgery.展开更多
Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of...Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of the trigeminal nerve and enter the cornea at the limbus radially from all directions toward the central cornea at the level of anterior and middle stroma.The subepithelial nerve plexus lies at the interface between the Bowman layer and anterior stroma.They then divide into smaller branches and turn 90°toward Bowman’s layer(Muller et al.,2003),travelling between Bowman’s layer and the basal epithelial layer and forming the sub-basal nerve plexus(Muller et al.,2003).展开更多
Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropath...Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.展开更多
AIM： To study the effect of celecoxib （CXB） on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model.METHODS： Six-week-old male Sprague-Dawley rats were randomly d...AIM： To study the effect of celecoxib （CXB） on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model.METHODS： Six-week-old male Sprague-Dawley rats were randomly divided into five groups, a non-treated group （NT）, a diethylnitrosamine-treated group （DEN）, a DEN＋CXB-treated group （DEN＋CXB）,and CXB 8 d-treated and CXB 32 d-treated groups. The effects of celecoxib on the enzymatic activities of CYP1A1, 2A, 2B1/2, and 2E1 were assessed in hepatic microsomes 24 h after DEN administration.Changes in CYPIA1 and CYP2B1/2 protein expression were also evaluated. The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite.RESULTS： DEN＋CXB administration produced a significant increase in the enzymatic activities ofCYP2B1/2 and 1A1, whereas it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a significant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times （CXB 32 d group）,the enzymatic activities were increased in a similar pattern to those in the DEN＋CXB group. The observed increase in the enzymatic activities in the DEN＋CXB group was accompanied by an increase in the CYP2B1/2 protein levels; no changes were observed in the levels of CYPIA1. In vitro, CXB increased the denitrosation of DEN, a pathway of metabolic detoxification. The addition of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN.CONCLUSION： These results suggest that the mechanism of action of CXB involves enhancement of the detoxification of DEN by an increasing denitrosation via CYP2B1/2.展开更多
The penetration behavior of topical substances in the skin not only relates to the transdermal delivery efficiency but also involves the safety and therapeutic effect of topical products,such as sunscreen and hair gro...The penetration behavior of topical substances in the skin not only relates to the transdermal delivery efficiency but also involves the safety and therapeutic effect of topical products,such as sunscreen and hair growth products.Researchers have tried to illustrate the transdermal process with diversified theories and technologies.Directly observing the distribution of topical substances on skin by characteristic imaging is the most convincing approach.Unfortunately,fluorescence labeling imaging,which is commonly used in biochemical research,is limited for transdermal research for most topical substances with a molecular mass less than 500 Da.Label-free imaging technologies possess the advantages of not requiring any macromolecular dyes,no tissue destruction and an extensive substance detection capability,which has enabled rapid development of such technologies in recent years and their introduction to biological tissue analysis,such as skin samples.Through the specific identification of topical substances and endogenous tissue components,label-free imaging technologies can provide abundant tissue distribution information,enrich theoretical and practical guidance for transdermal drug delivery systems.In this review,we expound the mechanisms and applications of the most popular label-free imaging technologies in transdermal research at present,compare their advantages and disadvantages,and forecast development prospects.展开更多
Peripheral vision loss followed by ＂tunnel vision＂ and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma（POAG） and normotensive gl...Peripheral vision loss followed by ＂tunnel vision＂ and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma（POAG） and normotensive glaucoma（NTG）.These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells（RGCs） accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve.Since patients suffering from this glaucomatous optic neuropathy（GON） first notice visual impairment when they have lost 〉 40% of their RGCs,early diagnosis is the key to retard the progression of glaucoma.Elevated intraocular pressure（IOP）,low cerebrospinal and/or low intracranial fluid pressure,advancing age,and ethnicity are major risk factors associated with POAG.However,retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic,inflammatory,oxidative and mechanical insults also contribute to vision loss in POAG/GON.Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs,combination drug products,and surgical interventions.Two recently approved multi-pharmacophoric drugs（e.g.,rho kinase inhibitor,Netarsudil;a drug conjugate,Latanoprostene Bunod） and novel aqueous humor drainage devices（i Stent and Cy Pass） are also gaining acceptance for treating POAG/NTG.Neuroprotective and regenerative agents,coupled with electroceutical,mechanical support systems,stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON.The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures,thereby providing a gain of function of the visual system for the glaucoma patients.展开更多
The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders,such as androgenetic alopecia(AGA)and acne vulga...The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders,such as androgenetic alopecia(AGA)and acne vulgaris.Hair follicle-targeting drug delivery systems allow for controlled drug release and enhance therapeutic efficacywithminimal side effects,exerting a promising method for themanagement of hair follicle-associated dysfunctions.Therefore,they have obtained much attention in several fields of research in recent years.This review gives an overviewof potential follicle-targeting drug delivery formulations currently applied based on the particularities of the hair follicles,including a comprehensive assessment of their preclinical and clinical performance.展开更多
In the context of the geometric model of particles (PGM), we show two different forms of the structure of the quark positions making up the neutron: first, an ordinary form, while the second is a “dark” form (diffic...In the context of the geometric model of particles (PGM), we show two different forms of the structure of the quark positions making up the neutron: first, an ordinary form, while the second is a “dark” form (difficult to detect). By the “dark” form we attempt of explaining the anomaly of the neutron lifetime (τ) in its decay observed in two different experiments as that in “bottle” and “in beam” and expressed by discrepancy between the two lifetimes (τ<sub>bottle</sub> ≠ τ<sub>beam</sub>). Using the structure equation of the dark neutron, we calculate its mass. In this framework, two problems can be resolved: the asymmetry between matter and antimatter and the abundance into universe of Lithium <sup>7</sup>Li than the <sup>6</sup>Li.展开更多
文摘Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.
基金funded by Directorate General of Higher Education,Reserach,and Technology,Ministry of Education,Culture,Reserach,and Technology of Indonesia(Grant number:1325/UN3.LPPM/PT.01.03/2023).
文摘Objectives:This study aimed to explore the voices of Indonesian migrant nurses on their retention in Japanese healthcare facilities.Methods:A descriptive qualitative study was conducted between June and September 2023.The snowball sampling method was utilized to recruit 22 Indonesian nurses working in healthcare facilities in seven prefectures of Japan.Semi-structured interviews were conducted based on their shared experiences.All interview data were audio-recorded,transcribed verbatim,and analyzed using thematic analysis.Results:Six prominent themes and 15 subthemes emerged:1)organizational factors(caring leader,involvement in decision making,career development,and participation in training);2)social support systems(group support,colleagues support and friend support);3)individual drive(lifelong learning and persistent);4)national policies(government support in public service and flexibility in finding a comfortable placement);5)family factors(positive support of child education and development and maintaining relationship with spouse);and 6)economic factors(staying due to high salary and increasing income streams).Conclusions:Retention of Indonesian migrant nurses in Japan is a multifaceted challenge that hinges on various interconnected factors.This study has gone some way toward enhancing our understanding of international nurse retention in the receiving countries.Corresponding supports at the individual,family,organizational,economic,social,and national policy levels should be considered to keep them in their destination countries.
基金Supported by the Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z20210442。
文摘BACKGROUND Ki-67 is a routine test item in clinical pathology departments.However,its prognostic value requires further investigation,especially in the context of research using machine learning(ML),which remains relatively underdeveloped.AIM To investigate the prognostic value of Ki-67 in cases of colorectal carcinoma(CRC)and explore the potential application of ML algorithms to predict the Ki-67 index.METHODS Case data and pathological sections from two centers were systematically collected.To analyze the prognostic value of the Ki-67 index in CRC,multiple cutoff values were established.Meanwhile,by virtue of the histological features presented in the hematoxylin and eosin-stained CRC images,three mainstream ML algorithms,support vector machine(SVM),random forest(RF),and eXtreme gradient boosting(XGBoost)were employed to construct prediction models.Subsequently,the potential of these algorithms to classify and predict the Ki-67 index was explored.RESULTS Non-parametric tests revealed that Ki-67≥40%correlated with a high histological grade(P=0.017),deficient mismatch repair protein status associated with≥50%-90%cutoffs(all P≤0.028),and≥80%linked to lymph node metastasis(P=0.006).Kaplan-Meier analysis showed that Ki-67≥50%predicted higher survival(log-rank P=0.0299,hazard ratio=2.142),with no differences for other cutoffs.COX regression identified the Ki-67 positive rate as a significant predictor(P=0.027,hazard ratio=2.583),while other variables had no association.In algorithmic model predictions,the SVM,RF,and XGBoost models achieved training area under the curve(AUC)values of 0.851,0.948,and 0.872,respectively,with corresponding test set AUC values of 0.795,0.755,and 0.750,respectively.During external validation,their AUC values for predicting Ki-67 status reached 0.757,0.749,and 0.783,respectively.CONCLUSION In algorithmic model predictions,the SVM,RF,and XGBoost models achieved training AUC values of 0.851,0.948,and 0.872,respectively,with corresponding test set AUC values of 0.795,0.755,and 0.750,respectively.During external validation,their AUC values for predicting Ki-67 status reached 0.757,0.749,and 0.783,respectively.
文摘Endothelial keratoplasty(EK)is defined as an umbrella term comprising methods for selective surgical replacement of corneal endothelium and adjacent corneal tissue,which retains healthy portions of a patient's cornea while replacing diseased innermost corneal layer(s)with healthy donor tissue,to achieve corneal dehydration and transparency before the onset of irreversible stromal edema and permanent loss of corneal clarity.Recently,the pathophysiology of corneal decompensation is increasingly being researched upon.Consequent improvement in pharmacotherapy is progressively leading to reduction in the indications of EK.In addition,EK techniques have progressed towards using thinner tissue,optimizing visual outcomes.Improvements have enabled better donor tissue formulation,usage,and attachment,and surgical modifications have enhanced the tissue utilization in difficult clinical scenarios lowering failure and rejection.However,challenges are encountered in various complex clinical scenarios in-cluding eyes with prior intraocular surgery,complex anterior chamber anatomy,glaucoma,ocular surface disease etc.These complexities demand tailored surgical strategies,including modifications in graft handling,instru-mentation,and postoperative management to ensure success.Attention to these details and addressing patient-specific factors can help improve outcomes in these difficult cases.The choice of procedure depends on multiple factors,including the surgeon's experience,patient's ocular anatomy,and the specific clinical scenario.This review article encompasses the recent developments in this field presenting a comprehensive picture of our modern understanding of the indications,contraindications,surgical techniques,clinical situations,community aspects and future directions pertaining to EK.
文摘Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.
基金National Key R&D Program of China:Research on the Functional Characteristics of"Special Effects"and"Common Effects"of Acupoints(No.2019YFC1709001)the National Natural Science Foundation of China:Study on the Immune Mechanisms of Macrophage M1/M2 Polarization in the Treatment of Rheumatoid Arthritis by Moxibustion"Strengthening Body Resistance and Eliminating Evil"(No.81973959)+3 种基金Research on"ImmuneInflammation"Molecular Signal Regulation of NLRP3 Inflammasomes in RA with Moxibustion Treatment(No.81774435)Foundation of Sichuan Provincial Administration of Traditional Chinese Medicine:Research on the Mechanism of MIF-GC Rhythm in the Anti-inflammatory Effect of Moxibustion in Treating Rheumatoid Arthritis(No.2018JC007)Science and Technology Innovation Seedling Project of Sichuan Province,China:based on Macrophage M1 Polarization Signaling Pathway TLR4-MyD88-NF-κB and Its Regulatory Molecule TIM-3 Exploring the Effect Mechanism of Moxibustion on Experimental RA Model(No.2022037)Chengdu University of Traditional Chinese Medicine Foundation:Study on the Mechanism of"MIF-target Protein-GC-inflammation"in the AntiInflammatory Effect of Moxibustion in the Treatment of RA(No.QNXZ2018034)。
文摘OBJECTIVE:To test the hypothesis that moxibustion may inhibit rheumatoid arthritis(RA)synovial inflammation by regulating the expression of macrophage migration inhibitory factor(MIF)/glucocorticoids(GCs).METHODS:Fifty male Sprague-Dawley rats were randomly divided into five groups(n=10 each):blank Control(CON)group,RA Model(RA)group,Moxibustion(MOX)group,MIF inhibitor(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester(ISO-1)group,and Moxibustion+MIF inhibitor ISO-1(MOX+ISO-1)group.Rats in the ISO-1 group and ISO-1+MOX group were intraperitoneally injected with the inhibitor ISO-1.The rats in the RA group,ISO-1 group,MOX group,and ISO-1+MOX group were injected with Freund's complete adjuvant(FCA)in the right hind footpad to establish an experimental RA rat model.In the MOX group and MOX+ISO-1 group,rats were treated with Moxa.The thickness of the footpads of the rats in each group was measured at three-time points before,after modeling and after moxibustion treatment.The contents of serum MIF,corticosterone(CORT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by enzyme-linked immunosorbent assay;and the contents of synovial MIF were detected by Western blot.Hematoxylin-eosin(HE)staining method was used to observe the pathological changes of synovial tissue under a section light microscope,and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease.RESULTS:Moxibustion was found to reduce the level of MIF and alleviate inflammation in RA rats in this study.In addition,after inhibiting the expression of MIF,the level of CORT increased,and the level of TNF-α decreased.Treating RA rats with inhibited MIF by moxibustion,the level of CORT was almost unchanged,but the level of TNF-α further decreased.The correlation analysis data suggested that MIF was positively related to the expression of TNF-α and negatively correlated with the expression of CORT.CONCLUSION:Reducing MIF to increase CORT and decrease TNF-α by moxibustion treatment in RA.MIF may be a factor for moxibustion to regulate the expression of CORT,but the expression of TNF-α is due to the incomplete regulation of the MIF.This study added to the body of evidence pointing to moxibustion's antiinflammatory mechanism in the treatment of RA.
基金Grants from the National Natural Science Foundation of China:Study on the Immune Mechanism of Macrophages 1/Macrophages 2 Polarization of Macrophages Treated with Moxibustion"Strengthening the Body and Expelling Pathogenic Qi"for"Struggle Between Healthy Qi and Pathogenic Qi"in Rheumatoid Arthritis(No.81973959)the National Key R&D Program of China:a Comparative Study of Moxibustion at Zusanli(ST36)on the Polarization of Knee Synovial Macrophage in Kneeosteoar-thritis and Rheumatoid Arthritis Rat Models(No.2019YFC1709001)+2 种基金the National Natural Science Foundation of China:Study on the Regulatory Mechanism of the"Immune-Inflammation"Molecular Signal of the Nucleotide—Binding Oligomerization Domain,Leucine rich Repeat and Pyrin domain containing Proteins 3 Inflammasome Treated by Moxibustion for Rheumatoid Arthritis(No.81774435)the Foundation of Chengdu University of Traditional Chinese Medicine:Study on the Mechanism of"Macrophage Migration Inhibitory Factor-Target Protein-Glucocorticoid-Inflammation"in Moxibustion Treatment and Anti-inflammatory Effect of Rheumatoid Arthritis(No.QNXZ2018034)the Science and Technology Innovation Seedling Project of Sichuan Province:Exploring the Effector Mechanism of Moxibustion Treatment in the Experimental Rheumatoid Arthritis Model based on the Macrophage Macrophages 1 Polarization Signaling Pathway Toll-like Receptors 4-Maximum Tolerated Dose 88-Nuclear Factor-Kappa B and its Regulatory Molecule T Cell Immunoglobulin and Mucin Domain-containing Protein 3(No.2022037)。
文摘OBJECTIVE:To determine whether moxibustion had an anti-inflammatory effect on rheumatoid arthritis(RA)by regulating Annexin 1 expression and interfering with the phospholipaseA2 signaling pathway.METHODS:Thirty male Sprague-Dawley rats were randomly categorized into five groups(six rats per group):blank control(CON)group,RA model(RA)group,moxibustion(MOX)group,Annexin 1 lentiviral intervention(RNAi-Anxa1)group,and Annexin 1 lentiviral intervention+moxibustion(RNAi-Anxa1+MOX)group.The rats in the RNAi-Anxa1 and the RNAi-Anxa1+MOX groups were injected with the lentiviral vector-mediated RNAi-Anxa1 into the rat foot pad.An experimental RA rat model was established by injecting Freund's complete adjuvant(FCA)into the RA,MOX,RNAi-Anxa1,and RNAi-Anxa1+MOX groups.Rats in the MOX and RNAiAnxa1+MOX groups received moxibustion treatment.After modeling,using moxibustion“Shenshu(BL23)”and“Zusanli(ST36)”,each point is 5 times,bilateral alternating,once a day,6 times for a course of treatment,between the courses of rest for a one day.A total of three treatment courses were conducted.Both bilateral pad thicknesses were measured using Vernier calipers on experimental days 1,7,14,21,and 28.The expression of cPLA2αsignaling in the synovium of diseased joints was observed using Western blot.The pathology of the rat ankle synovium was observed using hematoxylineosin(HE)staining.Interleukin(IL)-1β,IL-10,prostaglandin E2(PGE2),and leukotriene B4(LTB4)were detected using enzyme-linked immunosorbent assay.RESULTS:Moxibustion increased the levels of Annexin 1 and decreased the inflammatory response in rats with RA.After increasing the expression of Annexin 1,the phosphorylated expression of cPLA2αwas inhibited,the serum levels of IL-1β,PGE2,and LTB4 decreased,and the level of IL-10 increased.In moxibustion treated RA rats after the Annexin 1 lentiviral intervention,the serum levels of IL-1β,PGE2,LTB4,and IL-10 were almost unchanged.CONCLUSION:Moxibustion enhanced the negative regulation of the cPLA2αsignaling pathway,increased the synovial Annexin 1 expression,inhibited the cPLA2αsignaling pathway,indirectly inhibited the expression of downstream inflammatory factors,and played a role in reducing inflammation.
文摘Despite the profound cultural and medicinal heritage of traditional African medicines (TAM), their global recognition remains notably limited. This study investigates the factors behind this issue, focusing on cultural perceptions, scientific validation, regulatory frameworks, and pharmaceutical industry influence. Utilizing a systematic literature review (SLR) to provide a thorough and structured overview, the research addresses these factors with transparency and reproducibility. Key findings reveal that negative cultural perceptions, the dominance of Western medicine, and skepticism towards traditional healers, especially in urban and educated populations, marginalize TAM. Additionally, religious beliefs and historical influences, such as colonialism, further devalue indigenous knowledge systems. The study also highlights a significant lack of scientific research and clinical trials, which challenges the conventional validation of TAM’s efficacy. Moreover, inconsistent international and national regulatory frameworks and the pharmaceutical industry’s dominance impede TAM’s integration into global healthcare systems. To enhance TAM’s credibility and global acceptance, the study advocates for standardized regulatory policies, increased scientific research, and a reevaluation of intellectual property laws. This shift towards a more inclusive and integrative approach in global health systems could bridge the gap between traditional and modern medical practices, promoting a more holistic understanding of health and wellness.
文摘This paper shows a didactic model (PGM), and not only, but representative of the Hadrons described in the Standard Model (SM). In this model, particles are represented by structures corresponding to geometric shapes of coupled quantum oscillators (IQuO). By the properties of IQuO one can define the electric charge and that of color of quarks. Showing the “aurea” (golden) triangular shape of all quarks, we manage to represent the geometric combinations of the nucleons, light mesons, and K-mesons. By the geometric shape of W-bosons, we represent the weak decay of pions and charged Kaons and neutral, highlighting in geometric terms the possibilities of decay in two and three pions of neutral Kaon and the transition to anti-Kaon. In conclusion, from this didactic representation, an in-depth and exhaustive phenomenology of hadrons emerges, which even manages to resolve some problematic aspects of the SM.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular diseases independently of other risk factors.However,data on its effect on cardiovascular outcomes in coronavirus disease 2019(COVID-19)hospitalizations with varied obesity levels is scarce.Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.AIM To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity.METHODS COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease-10 CM codes in the 2020 National Inpatient Sample database.Overweight and Obesity Classes Ⅰ,Ⅱ,and Ⅲ(body mass index 30-40)were compared.Major adverse cardiac and cerebrovascular events(MACCE)(all-cause mortality,acute myocardial infarction,cardiac arrest,and stroke)were compared between groups.Multivariable regression analyses adjusted for sociodemographic,hospitalization features,and comorbidities.RESULTS Our analysis comprised 13260 hospitalizations,7.3% of which were overweight,24.3% Class Ⅰ,24.1% Class Ⅱ,and 44.3% Class Ⅲ.Class Ⅲ obesity includes younger patients,blacks,females,diabetics,and hypertensive patients.On multivariable logistic analysis,Class Ⅲ obese patients had higher risks of MACCE,inpatient mortality,and respiratory failure than Class Ⅰ obese patients.Class Ⅱ obesity showed increased risks of MACCE,inpatient mortality,and respiratory failure than Class I,but not significantly.All obesity classes had non-significant risks of MACCE,inpatient mortality,and respiratory failure compared to the overweight group.CONCLUSION Class Ⅲ obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class Ⅰ.Using the overweight group as the reference,unfavorable outcomes were not significantly different.Morbid obesity had a greater risk of MACCE regardless of the referent group(overweight or Class Ⅰ obese)compared to overweight NAFLD patients admitted with COVID-19.
基金supported by the National Technologies R&D Program of China (2006BAD01A02)the Excellent Medium-Youth Scientist Scientific Research Reward Fundation of Shandong Province, China (BS2009NY036)the Youth Science and Technology Creative Fundation Item of Shandong Agricultural University, China
文摘The anthocyanin pigment extracted from green-wheat-bran was studied to identify its antioxidant activity.The antioxidant activities of the pigment were evaluated by anti-lipid peroxidation,total antioxidant activity （TAA）,superoxide anion radical scavenging activity （SARSA）,active oxygen scavenging activity （AOSA）,and DPPH （1,1-diphenyl-2 picrylhydrazyl free radical） radical scavenging activity.The results showed that the pigment had higher antioxidant activity and TAA,SARSA,AOSA and DPPH.scavenging activities at a certain concentration than Vc （antiscorbutic vitamin,vitamin C）,and the capacity increased with the increase of pigment concentration.Its TAA was 51.06 U mL-1,1.73 times of Vc,and SARSA 18 025.21 U mL-1,2.26% higher than Vc,and AOSA 3 776.31 U mL-1,1.24 times of Vc.As to the DPPH.scavenging activity of the pigment,there was a trend that higher concentration performed higher activity significantly improved with the company of Vc.The pigment showed significant antioxidant activities evaluated by different assays.Results will provide a better understanding on antioxidant activity of green wheat and allow the screening or breeding of green wheat varieties with higher antioxidant activity for food processing.
文摘Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy.Following laser refractive surgery,the corneal nerves,epithelial and stromal cells release neuromediators,including neurotrophins,neuropeptides and neurotransmitters.Notably,nerve growth factor,substance P,calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration.Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced.In this review,we will discuss the(1)Functions of neuromediators and their physiological and clinical significance;(2)Changes in the neuromediators following various laser refractive surgeries;(3)Correlation between neuromediators,ocular surface health and corneal nerve status;and(4)Future directions,including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery,and as adjuncts to aid in corneal regeneration after laser refractive surgery.
文摘Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of the trigeminal nerve and enter the cornea at the limbus radially from all directions toward the central cornea at the level of anterior and middle stroma.The subepithelial nerve plexus lies at the interface between the Bowman layer and anterior stroma.They then divide into smaller branches and turn 90°toward Bowman’s layer(Muller et al.,2003),travelling between Bowman’s layer and the basal epithelial layer and forming the sub-basal nerve plexus(Muller et al.,2003).
文摘Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.
基金Supported by Consejo Nacional de Ciencia y Tecnología (Mexico),grant 39525-M,and scholarship 119303 (M.E.S.N.)
文摘AIM： To study the effect of celecoxib （CXB） on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model.METHODS： Six-week-old male Sprague-Dawley rats were randomly divided into five groups, a non-treated group （NT）, a diethylnitrosamine-treated group （DEN）, a DEN＋CXB-treated group （DEN＋CXB）,and CXB 8 d-treated and CXB 32 d-treated groups. The effects of celecoxib on the enzymatic activities of CYP1A1, 2A, 2B1/2, and 2E1 were assessed in hepatic microsomes 24 h after DEN administration.Changes in CYPIA1 and CYP2B1/2 protein expression were also evaluated. The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite.RESULTS： DEN＋CXB administration produced a significant increase in the enzymatic activities ofCYP2B1/2 and 1A1, whereas it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a significant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times （CXB 32 d group）,the enzymatic activities were increased in a similar pattern to those in the DEN＋CXB group. The observed increase in the enzymatic activities in the DEN＋CXB group was accompanied by an increase in the CYP2B1/2 protein levels; no changes were observed in the levels of CYPIA1. In vitro, CXB increased the denitrosation of DEN, a pathway of metabolic detoxification. The addition of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN.CONCLUSION： These results suggest that the mechanism of action of CXB involves enhancement of the detoxification of DEN by an increasing denitrosation via CYP2B1/2.
文摘The penetration behavior of topical substances in the skin not only relates to the transdermal delivery efficiency but also involves the safety and therapeutic effect of topical products,such as sunscreen and hair growth products.Researchers have tried to illustrate the transdermal process with diversified theories and technologies.Directly observing the distribution of topical substances on skin by characteristic imaging is the most convincing approach.Unfortunately,fluorescence labeling imaging,which is commonly used in biochemical research,is limited for transdermal research for most topical substances with a molecular mass less than 500 Da.Label-free imaging technologies possess the advantages of not requiring any macromolecular dyes,no tissue destruction and an extensive substance detection capability,which has enabled rapid development of such technologies in recent years and their introduction to biological tissue analysis,such as skin samples.Through the specific identification of topical substances and endogenous tissue components,label-free imaging technologies can provide abundant tissue distribution information,enrich theoretical and practical guidance for transdermal drug delivery systems.In this review,we expound the mechanisms and applications of the most popular label-free imaging technologies in transdermal research at present,compare their advantages and disadvantages,and forecast development prospects.
文摘Peripheral vision loss followed by ＂tunnel vision＂ and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma（POAG） and normotensive glaucoma（NTG）.These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells（RGCs） accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve.Since patients suffering from this glaucomatous optic neuropathy（GON） first notice visual impairment when they have lost 〉 40% of their RGCs,early diagnosis is the key to retard the progression of glaucoma.Elevated intraocular pressure（IOP）,low cerebrospinal and/or low intracranial fluid pressure,advancing age,and ethnicity are major risk factors associated with POAG.However,retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic,inflammatory,oxidative and mechanical insults also contribute to vision loss in POAG/GON.Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs,combination drug products,and surgical interventions.Two recently approved multi-pharmacophoric drugs（e.g.,rho kinase inhibitor,Netarsudil;a drug conjugate,Latanoprostene Bunod） and novel aqueous humor drainage devices（i Stent and Cy Pass） are also gaining acceptance for treating POAG/NTG.Neuroprotective and regenerative agents,coupled with electroceutical,mechanical support systems,stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON.The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures,thereby providing a gain of function of the visual system for the glaucoma patients.
文摘The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders,such as androgenetic alopecia(AGA)and acne vulgaris.Hair follicle-targeting drug delivery systems allow for controlled drug release and enhance therapeutic efficacywithminimal side effects,exerting a promising method for themanagement of hair follicle-associated dysfunctions.Therefore,they have obtained much attention in several fields of research in recent years.This review gives an overviewof potential follicle-targeting drug delivery formulations currently applied based on the particularities of the hair follicles,including a comprehensive assessment of their preclinical and clinical performance.
文摘In the context of the geometric model of particles (PGM), we show two different forms of the structure of the quark positions making up the neutron: first, an ordinary form, while the second is a “dark” form (difficult to detect). By the “dark” form we attempt of explaining the anomaly of the neutron lifetime (τ) in its decay observed in two different experiments as that in “bottle” and “in beam” and expressed by discrepancy between the two lifetimes (τ<sub>bottle</sub> ≠ τ<sub>beam</sub>). Using the structure equation of the dark neutron, we calculate its mass. In this framework, two problems can be resolved: the asymmetry between matter and antimatter and the abundance into universe of Lithium <sup>7</sup>Li than the <sup>6</sup>Li.
