Microvascular alterations of the ocular surface and retina in connective tissue disease-related interstitial lung disease

AIM:To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease(CTD-ILD)and healthy controls(HCs)by optical coherence tomography angiography(OCTA)and to investigate the changes in microvascular density in abnormal eyes.METHODS:For a retrospective case-control study,a total of 16 patients(32 eyes)diagnosed with CTD-ILD were selected as the ILD group.The 16 healthy volunteers with 32 eyes,matched in terms of age and sex with the patients,were recruited as control group.The macular retina’s superficial retinal layer(SRL)and deep retinal layer(DRL)were examined and scanned using OCTA in each individual eye.The densities of retinal microvascular(MIR),macrovascular(MAR),and total microvascular(TMI)were calculated and compared.Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods:central annuli segmentation method(C1-C6),hemispheric segmentation method[uperior right(SR),superior left(SL),inferior left(IL),and inferior right(IR)],and Early Treatment Diabetic Retinopathy Study(ETDRS)methods[superior(S),inferior(I),left(L),and right(R)].The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis.RESULTS:The OCTA data demonstrated a statistically significant difference(P<0.05)in macular retinal microvessel density between the two groups.Specifically,in the SRL and DRL analyses,the ILD group exhibited significantly lower surface density of MIR and TMI compared to the HCs group(P<0.05).Furthermore,using the hemispheric segmentation method,the ILD group showed notable reductions in SL,SR,and IL in the superficial retina(P<0.05),as well as marked decreases in SL and IR in the deep retina(P<0.05).Similarly,when employing the ETDRS method,the ILD group displayed substantial drops in superficial retinal S and I(P<0.05),along with notable reductions in deep retinal L,I,and R(P<0.05).In the central annuli segmentation method,the ILD group exhibited a significant decrease in the superficial retinal C2-4 region(P<0.05),whereas the deep retina showed a notable reduction in the C3-5 region(P<0.05).Additionally,there was an observed higher positive likelihood ratio in the superficial SR region and deep MIR.Furthermore,there was a negative correlation between conjunctival vascular density and both deep and superficial retinal TMI(P<0.001).CONCLUSION:Patients with CTD-ILD exhibits a significantly higher conjunctival vascular density compared to the HCs group.Conversely,their fundus retinal microvascular density is significantly lower.Furthermore,CTD-ILD patients display notably lower superficial and deep retinal vascular density in comparison to the HCs group.The inverse correlation between conjunctival vascular density and both superficial and deep retinal TMI suggests that detecting subtle changes in ocular microcirculation could potentially serve as an early diagnostic indicator for connective tissue diseases,thereby enhancing disease management.

Immunoglobulin G4-related spinal pachymeningitis:A case report

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a complex immune-mediated condition that causes fibrotic inflammation in several organs.A significant clinical feature of IgG4-RD is hypertrophic pachymeningitis,which manifests as inflammation of the dura mater in intracranial or spinal regions.Although IgG4-RD can affect multiple areas,the spine is a relatively rare site compared to the more frequent involvement of intracranial structures.CASE SUMMARY A 70-year-old male presented to our hospital with a two-day history of fever,altered mental status,and generalized weakness.The initial brain magnetic resonance imaging(MRI)revealed multiple small infarcts across various cerebral regions.On the second day after admission,a physical examination revealed motor weakness in both lower extremities and diminished sensation in the right lower extremity.Electromyographic evaluation revealed findings consistent with acute motor sensory neuropathy.Despite initial management with intravenous immunoglobulin for presumed Guillain-Barrésyndrome,the patient exhibited progressive worsening of motor deficits.On the 45th day of hospitalization,an enhanced MRI of the entire spine,focusing specifically on the thoracic 9 to lumbar 1 vertebral level,raised the suspicion of IgG4-related spinal pachymeningitis.Subsequently,the patient was administered oral prednisolone and participated in a comprehensive rehabilitation program that included gait training and lower extremity strengthening exercises.CONCLUSION IgG4-related spinal pachymeningitis,diagnosed on MRI,was treated with corticosteroids and a structured rehabilitation regimen,leading to significant improvement.

Evaluation of internal void related defects in reinforced concrete slab using electromagnetic wave properties

This study aims to develop a damage-detection algorithm based on the electromagnetic wave properties inside a reinforced concrete structure.The proposed method involves employing two algorithms based on data measured using ground-penetrating radar—a common electromagnetic wave method in civil engineering.The possible defect area was identified based on the energy dissipated by the damage in the frequency-wavenumber domain,with the damage localized using the calculated relative permittivity of the measurements.The proposed method was verified through a finite difference time-domain-based numerical analysis and a testing slab with artificial damage.As a result of verification,the proposed method quickly identified the presence of damage inside the concrete,especially for honeycomb-like defects located at the top of the rebar.This study has practical significance in scanning structures over a large area more quickly than other non-destructive testing methods,such as ultrasonic methods.

Cost analysis of radical resection of malignant breast tumors under the China Healthcare Security Diagnosis Related Groups payment system

BACKGROUND Breast cancer is one of the most common malignant tumors in women worldwide and poses a severe threat to their health.Therefore,this study examined patients who underwent breast cancer surgery,analyzed hospitalization costs and structure,and explored the impact of China Healthcare Security Diagnosis Related Groups(CHS-DRG)management on patient costs.It aimed to provide medical institutions with ways to reduce costs,optimize cost structures,reduce patient burden,and improve service efficiency.AIM To study the CHS-DRG payment system’s impact on breast cancer surgery costs.METHODS Using the CHS-DRG(version 1.1)grouping criteria,4073 patients,who underwent the radical resection of breast malignant tumors from January to December 2023,were included in the JA29 group;1028 patients were part of the CHS-DRG payment system,unlike the rest.Through an independent sample t-test,the length of hospital stay as well as total hospitalization,medicine and consumables,medical,nursing,medical technology,and management expenses were compared.Pearson’s correlation coefficient was used to test the cost correlation.RESULTS In terms of hospitalization expenses,patients in the CHS-DRG payment group had lower medical,nursing,and management expenses than those in the diagnosis-related group(DRG)non-payment group.For patients in the DRG payment group,the factors affecting the total hospitalization cost,in descending order of relevance,were medicine and consumable costs,consumable costs,medicine costs,medical costs,medical technology costs,management costs,nursing costs,and length of hospital stay.For patients in the DRG nonpayment group,the factors affecting the total hospitalization expenses in descending order of relevance were medicines and consumable expenses,consumable expenses,medical technology expenses,the cost of medicines,medical expenses,nursing expenses,length of hospital stay,and management expenses.CONCLUSION The CHS-DRG system can help control and reduce unnecessary medical expenses by controlling medicine costs,medical consumable costs,and the length of hospital stay while ensuring medical safety.

Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways

Background and objective:In northern China's cold regions,the prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)exceeds 50%,significantly higher than the national and global rates.MASLD is an important risk factor for cardiovascular and cerebrovascular diseases,including coronary heart disease,stroke,and tumors,with no specific therapeutic drugs currently available.The ethanol extract of cassia seed(CSEE)has shown promise in lowering blood lipids and improving hepatic steatosis,but its mechanism in treating MASLD remains underexplored.This study aims to investigate the therapeutic effects and mechanisms of CSEE.Methods:MASLD models were established in male Wistar rats and golden hamsters using a high fat diet(HFD).CSEE(10,50,250 mg/kg)was administered via gavage for six weeks.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),as well as liver TC and TG,were measured using biochemical kits.Histopathological changes in the liver were evaluated using Oil Red O staining,Hematoxylin-eosin(H&E)staining,and transmission electron microscopy(TEM).HepG2 cell viability was assessed using the cell counting kit-8(CCK8)and Calcein-AM/PI staining.Network pharmacology was used to analyze drug-disease targets,and western blotting was used to confirm these predictions.Results:CSEE treatment significantly reduced serum levels of TC,TG,LDL-C,ALT,and AST,and improved liver weight,liver index,and hepatic lipid deposition in rats and golden hamsters.In addition,CSEE alleviated free fatty acid(FFA)-induced lipid deposition in HepG2 cells.Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK,p-ACC,PPARα,CPT1A,PI3K P110 and p-AKT,while decreasing the protein levels of SREBP1,FASN,C/EBPα,and PPARγ,thus improving hepatic lipid metabolism and reducing lipid deposition.The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro.Conclusion:CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK,PPARα,and PI3K/AKT signaling pathways.

The Prevalence of Overweight/Obesity and Related Comorbidities among HIV-Positive and HIV-Negative Patients Attending the Same Clinics in Gaborone, Botswana

Context: Antiretroviral therapy (ART) helps restore the health status of people living with HIV (PLHIV). Likewise, it increases the risk of overweight/obesity and related comorbidities among the recipients. In countries like Botswana where ±84% of PLHIV is on ART, the paucity of data comparing overweight/obesity between HIV-positive on ART and HIV-negative patients may impede clinical and policy decision-making. This study sought to estimate and compare: i) the prevalence of overweight/obesity between HIV-positive on ART and HIV-negative patients;ii) the prevalence of hypertension (HTN), diabetes mellitus (DM)/coronary heart disease (CHD) between HIV-positive patients on ART and HIV-negative patients attending same outpatient departments of general clinics in Gaborone, Botswana. Patients and Methods: Five hundred eighty-one (581) outpatients were recruited in four major clinics of Gaborone, Botswana, between June and July 2019;294 or 51% of them were HIV-negative and 287 or 49% were HIV-positive on ART. The prevalence of overweight/obesity and of HTN and DM/CHD were calculated and examined using stratified analysis. Subgroups were compared using Chi-square analysis with Yates correction or Fisher exact test and t-student test for continuous data. Results: Major findings after stratification of the study population by HIV status were: i) the prevalence of all categories of (BMI), including overweight/obesity, were comparable between HIV-negative-patients and HIV-positive. In fact, there were 24 (8.0%) cases of underweight among HIV-negative-Patients and 15(5%) cases among HIV-positive patients, p = 0.2;145 (49%) HIV-negative-patients and 128 (45%) HIV-positive, p = 0.07 cases of normal weight;72 (25%) HIV-negative-patients and 87 (30%) HIV-positive, p = 0.08, were overweight;53 (18%) HIV-negative-patients and 57 (20%) HIV-positive, p = 0.12, were obese;125 (43%) HIV-negative patients and 144 (50%) HIV-positive, p=0.06 were overweight/obese;ii) the prevalence of HTN and DM/CHD among HIV-positive-patients were significantly lower (p < 0.05) compared to HIV-negative patients: There were 32 (10.9%) cases of HTN among HIV-negative patients compared to 18 (6.3%) cases of HTN among HIV-positive patients, p = 0.001;32 (11%) cases of DM/CHD HIV-negative patients compared to 4 (1.4%) cases of DM/CHD among HIV-positive patients, p = 0.001. Conclusion: the prevalence of overweight/obesity observed between HIV-negative and HIV-positive patients may suggest that the two groups shared the same exposure factors. That HTN and DM/CHD prevalence was lower among HIV-positive compared to HIV-negative patients, is possibly due to interplay factors of ART, HIV or the host population. Further studies are, however, recommended for clarifications.

A related degree-based frequent pattern mining algorithm for railway fault data

It is of great significance to improve the efficiency of railway production and operation by realizing the fault knowledge association through the efficient data mining algorithm.However,high utility quantitative frequent pattern mining algorithms in the field of data mining still suffer from the problems of low time-memory performance and are not easy to scale up.In the context of such needs,we propose a related degree-based frequent pattern mining algorithm,named Related High Utility Quantitative Item set Mining(RHUQI-Miner),to enable the effective mining of railway fault data.The algorithm constructs the item-related degree structure of fault data and gives a pruning optimization strategy to find frequent patterns with higher related degrees,reducing redundancy and invalid frequent patterns.Subsequently,it uses the fixed pattern length strategy to modify the utility information of the item in the mining process so that the algorithm can control the length of the output frequent pattern according to the actual data situation and further improve the performance and practicability of the algorithm.The experimental results on the real fault dataset show that RHUQI-Miner can effectively reduce the time and memory consumption in the mining process,thus providing data support for differentiated and precise maintenance strategies.

Changes in acute and late toxicity and patient-reported health-related quality of life following radiotherapy in women with breast cancer:A 1-year longitudinal study

Objective:The objective of this study was to investigate the frequency of acute and late toxicities,as well as changes in the quality of life(QOL)for breast cancer patients following radiotherapy(RT).Materials and Methods:A total of 108 breast cancer women were recruited for this prospective study.Data were collected at various intervals;prior to,and 1,3,6 months,and 1 year after radiation therapy.The primary outcomes were toxicity radiation therapy oncology group/European Organization for Research and Treatment of Cancer(EORTC)criteria.Our secondary outcome was QOL,measured using EORTC QLQ-C30 and Edmonton Symptom Assessment Scale.We employed Friedman’s two-way analysis to evaluate the changes in QOL over the course of 1 year.Results:The early toxicities that are most commonly experienced include pharyngeal,skin,and mucous membrane toxicity.Late toxicities frequently involve skin and submucosal toxicity.To measure patient functionality,all functional subscale scores except for the patient’s emotional state increased over time compared to pre-RT.Symptoms of the patients,which were included in the QOL symptom scale,decreased during the follow-up period,except for fatigue;however,changes in pain,insomnia,and loss of appetite did not significantly change.We identified the analogous symptom profiles in Edmonton.Although patients’overall health scores declined in the 1st and 3rd months after radiotherapy(RT),they rebounded at 6 and 12 months.Conclusion:For breast cancer patients,RT did not adversely affect functional capacity or exacerbate symptoms,but persistent fatigue did increase during the observation period.Health-care professionals ought to devise strategies to assist patients with skin toxicity and fatigue.

A Germplasm Resource Repository:The Book Review of Illustrated Flora of Food Crops and Their Wild Related Plants in China

Illustrated Flora of Food Crops and Their Wild Related Plants in China systematically examines the botanical and morphological characteristics of China's major food crops,such as rice,wheat,corn,sweet potato,potato,mung bean,and buckwheat.Featuring more than 5000 color photos and 200 line drawings,it offers a comparative study that highlights the kinship and internal connections between cultivated and wild species.The book is an invaluable resource for breeders,offering a comprehensive morphological and genetic database that aids in the development of high-yielding,high-quality,and disease-resistant crop varieties.

The Impact of Finerenone on Changes in Pulse Wave Velocity, Arterial Pressure and Heart Related Deaths in Hemodialysis Patients—Study Perspective

The description in the abstract lacks clear logic and a comprehensive summary of this study, so please revise and improve it according to the design theme and main content of this study, and describe it in the order of (research background), purpose/aim, method, results and conclusions. The introduction of the abstract and preface is rather lengthy, but the summary of the whole study and the presentation of the research background are not perfect (mainly because the logic of the context is not clear and orderly), so it will appear a bit messy. Hope to be able to modify (this has been mentioned in the preliminary opinion). Cardiovascular events (CVE) pose a significant threat to individuals with end-stage renal disease (ESRD), yet these patients are often excluded from cardiovascular clinical trials, leaving prognostic factors associated with CVE in ESRD patients largely unexplored. Recent human studies have demonstrated elevated circulating aldosterone levels in ESRD patients, correlating with left ventricular hypertrophy. Additionally, animal models have shown improvements in uremic cardiomyopathy with spironolactone therapy, prompting interest in assessing the efficacy of spironolactone or eplerenone in reducing mortality and improving cardiovascular function in dialysis patients. Clinicians have historically been cautious about prescribing mineralocorticoid receptor antagonists (MRAs) to congestive heart failure patients with chronic kidney disease (CKD) due to hyperkalemia risk. However, the emergence of finerenone, a novel MR antagonist with a favorable safety profile and lower hyperkalemia risk, has renewed interest in MRA therapy in this population. Heart disease, including coronary artery disease, hypertension, and left ventricular failure, is alarmingly prevalent in dialysis patients, contributing significantly to elevated mortality rates compared to the general population. Arterial stiffness, as indicated by pulse wave velocity (PWV), progressively worsens with advancing CKD stages, peaking in severity among ESRD patients undergoing dialysis. High PWV serves as a crucial risk stratification tool in ESRD. Elevated NT-proBNP and BNP levels in ESRD patients are well-documented, with significant associations observed between baseline peptide concentrations and cardiovascular morbidity and mortality. By incorporating finerenone into our study, we aim to investigate its potential benefits in reducing arterial stiffness, lowering blood pressure, and ultimately mitigating heart-related mortality among hemodialysis patients. This study holds substantial implications for hypertension and cardiovascular risk management in this vulnerable patient population. Eligible participants must have been on chronic hemodialysis for at least three months, with ACE inhibitors or angiotensin receptor blockers included in their therapy at maximum tolerable doses. Serum potassium levels 5.7 mmol/L, left ventricular ejection fraction 50%, and PWV higher than age-estimated values are also prerequisites for study entry. Randomized allocation will be conducted using a permuted block design, stratified by center, with allocation communicated via signed study forms during initial examinations. All steps of this research will be conducted in accordance with the principles of the Helsinki Declaration.

A Cross-Sectional Study on The Prevalence of Anemia in Maintenance Hemodialysis and Peritoneal Dialysis Patients and Its Related Factors

Objective:To study the prevalence of anemia,the proportion of hemoglobin(Hb)levels,the treatment methods,and the influencing factors of Hb levels in maintenance hemodialysis(MHD)and peritoneal dialysis patients.Methods:In this study,602 patients with maintenance hemodialysis and continuous ambulatory peritoneal dialysis were enrolled from December 2020 to December 2022 in our hospital,and their medical records were collected and summarized.The main contents included the patient’s gender,age,primary disease,dialysis duration,dialysis method,the use of erythropoietic stimulating agents(ESA),intravenous iron,and laboratory tests.A Hb index exceeding 110 g/L was set as the standard for the prevalence of anemia.Results:The rate of anemia in patients undergoing blood purification was 83%.The proportion of ESA use was 84.1%,and the proportion of iron use was 76.7%,of which the proportion of intravenous iron used was 17.0%,and the proportion of folic acid used was 28.3%.Conclusion:The incidence of anemia in MHD patients was relatively high,with a low proportion of patients reaching the standard Hb levels.Risk factors include albumin(ALB)levels,iron storage,white blood cells,C-reactive protein,cholesterol,etc.Nutritional support,iron supplementation,and prevention of micro-inflammatory reactions can effectively promote the improvement of Hb indicators in dialysis patients to prevent anemia.

Analysis of Factors Related to Vasovagal Response in Apheresis Blood Donors and the Establishment of Prediction Model Based on BP Neural Network Algorithm

Objective:To analyze the factors related to vessel vasovagal reaction(VVR)in apheresis donors,establish a mathematical model for predicting the correlation factors and occurrence risk,and use the prediction model to intervene in high-risk VVR blood donors,improve the blood donation experience,and retain blood donors.Methods:A total of 316 blood donors from the Xi'an Central Blood Bank from June to September 2022 were selected to statistically analyze VVR-related factors.A BP neural network prediction model is established with relevant factors as input and DRVR risk as output.Results:First-time blood donors had a high risk of VVR,female risk was high,and sex difference was significant(P value<0.05).The blood pressure before donation and intergroup differences were also significant(P value<0.05).After training,the established BP neural network model has a minimum RMS error of o.116,a correlation coefficient R=0.75,and a test model accuracy of 66.7%.Conclusion:First-time blood donors,women,and relatively low blood pressure are all high-risk groups for VVR.The BP neural network prediction model established in this paper has certain prediction accuracy and can be used as a means to evaluate the risk degree of clinical blood donors.

Inferring Genome Ancestry and Estimating Molecular Relatedness Among 187 Chinese Maize Inbred Lines

The inference of genome ancestry and the estimation of molecular relatedness are of great importance for breeding efficiency and association studies. Seventy SSR loci, evenly distributed in 10 chromosomes, were assayed for polymorphism among 187 commonly used maize （Zea mays L.） inbreds which represent the genetic diversity in China. The identified 290 alleles served as raw data for estimating population structure using the coalescent linked loci, based on the ADMIXTURE model. Population number, K, has been inferred to be between five and seven. Specifying five subpopulations （K = 5） led to a distinct decrease and specifying K to be greater than six resulted in only minimal increases in the likelihood value. Therefore, population number, K, has been inferred into six subpopulations, which are PA, BSSS （includes Reid）, PB, Lan （Lancaster Sure Crop）, LRC （Luda Reb Cob, a Chinese landrace, and its derivatives）, and SPT （Si-ping-tou, a Chinese landrace and its derivatives）. The Kullback-Leibler distance of pairwise subpopulation was also inferred as n × p （187 ×6） Q matrices, which gave a detailed percentage of genetic composition of six subpopulations and molecular relatedness of each line. The genome-wide linkage disequilibrium （LD） indicated that the asso- ciation studies in QTLs and/or candidate genes might avoid nonfunctional and spurious associations, as most of the LD blocks were broken among diverse germplasm. The defined population structure has given us a clear genetic structure of these lines for breeding practice and established a good basis for association analysis.

QTL Mapping for the Sensitivity of the Traits Related to Outcrossing of Japonica Rice to Exogenous GA_3

[Objective] The research aimed to map QTL for the sensitivity of the traits related outcrosssing of Japonica rice to exogenous GA3 and provide theoretical basis for breeding and improving the high-sensitivity sterile line.[Method] Taking Japonica rice Xiushui 79 and C bao and their recombinant inbred line population 260 lines as test materials,the sensitivity of 4 traits related outcrossing to Exogenous GA3 and their QTL mapping were studied by using composite interval mapping..[Result]Three QTLs,which cont...

Non-tobacco Related Materials Control Mode of Export-oriented Tobacco

Non-tobacco related materials （NTRM） come from field production, tobacco stringing, grading and purchasing, affecting cigarette quality and having potential safety hazard. The research reviewed control on NTRM from source, production and processing to enhance use efficiency of raw materials and guarantee raw material safety.

Analysis on Fuji Apple Tree Structures and Related Factors under Different Pruning Modes

To determine the correlations between the tree structuresof Fuji apple with different pruning modes and each factor, the data about 3 tree structures which were free spindle short shoot, free spindle long shoot and slenderspindle short shoot in Xingtang County of Hebai Province were investigated, then by SPSS anal- ysis, the correlations between the taperingness and each growth factor of inserted small branch were compared. The results showed that the taperingness of central trunk of free spindle dwarf-shoot Fuji apple treeshad negative correlations with each factor of inserted small branch, while the taperingness of central trunk of free spin- dle long-shoot Fuji apple treeshad positive correlations with each factor of inserted small branch, the taperingness of central trunk of slenderspindle short-shootFuji ap- ple treeshad negative correlation with total thickness of inserted small branch, but had positive correlations with other factors. This study can provide a scientifictheo- retical basis for the pruning technology of high-density planting trees grafting by dwarfing self-rooted rootstock.

Development and Validation of Liquid Chromatographic Method for the Determination of the Related Substances of Rifampicin

A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic method for the determination of related substances of rifampicin is developed and validated. Rifampicin and its related substances, including rifamycin SV, rifampicin N-oxide and 3-formylrifamycin SV were separated using a Zorbax Eclipse C8, 250×4.6 mm(i.d), 5 μm column by isocratic elution at a flow rate of 1 mL·min -1. The detector was set at 254 nm. The mobile phase is a mixture of methanol-acetonitrile -0.075 mol·L -1 monopotassium phosphate -1.0 mol·L -1 citric acid (31:31:35:3, v/v). The method validation included accuracy, precision, linearity, sensitivity and stability. All results are shown to be acceptable.

Screening Rat Hypertension-Related Genes By Differential Display

ＳｃｒｅｅｎｉｎｇＲａｔＨｙｐｅｒｔｅｎｓｉｏｎ－ＲｅｌａｔｅｄＧｅｎｅｓＢｙＤｉｆｆｅｒｅｎｔｉａｌＤｉｓｐｌａｙＣａｏＹｕｑｉｎｇ曹宇清，ＺｈａｎｇＣｈｅｎｈｕｉ张晨晖，ＬｉＱｉａｎｈｏｎｇ李倩虹，ＸｕＰｉｎｇ徐平，ＺｈｏｕＡｉｒｕ周爱儒，ａｎｄ...

Autophagy-targeting modulation to promote peripheral nerve regeneration

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.