Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema

AIM:To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide(TA)in treating diabetic macular edema(DME)and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection.METHODS:Totally 67 DME patients(67 eyes)and 30 cataract patients(32 eyes)were enrolled as the DME group and the control group,respectively.The DME group was divided into the aflibercept group(34 cases)and the aflibercept combined with TA group(combined group,33 cases).The aqueous humor of both groups was collected during the study period.The aqueous levels of vascular endothelial growth factor(VEGF),monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),interleukin-8(IL-8),and interleukin-1β(IL-1β)were detected using a microsphere suspension array technology(Luminex 200TM).Aqueous cytokines,best-corrected visual acuity(BCVA),central macular thickness(CMT),and complications before and after treatment were compared between the aflibercept group and combined group.RESULTS:The concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group(all P<0.01).After 1mo of surgery,the concentrations of VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group(all P<0.01).The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment(P<0.01).However,the difference was not statistically significant after 3mo of treatment(P>0.05).CONCLUSION:The cytokines VEGF,MCP-1,IL-6,and IL-8 in the aqueous humor of DME patients are significantly increased.Aflibercept and aflibercept combined with TA have good efficacy in DME patients,can effectively reduce CMT,improve the patient’s vision,and have high safety.Aflibercept combined with TA can quickly downregulate the aqueous humor cytokines and help to relieve macular edema rapidly.However,the long-term efficacy is comparable to that of aflibercept alone.

Bone marrow edema in a postpartum female following ankle sprain: a case report

Bone marrow edema(BME)is characterized by an accumulation of interstitial fluid within the bone marrow,the cancellous,hematopoietic compartment within bones.[1]BME is divided into two principal categories:idiopathic or primary BME,with an unknown etiology,and secondary BME,which occurs as a result of an identifiable underlying pathology.[2]Although the prevalence of BME is not limited to specific demographic parameters,it shows a predilection for males or individuals assigned male at birth,predominantly aged between the ages of 30 and 60 years,especially in cases of bone marrow edema syndrome(BMES),a rare idiopathic variant.[3]The etiological spectrum of BME is diverse,including oncological entities(such as acute myeloid leukemia and osteosarcoma),degenerative diseases(such as osteoarthritis),infectious processes(osteomyelitis),ischemic conditions(avascular necrosis),metabolic dysfunctions(osteoporosis),inflammatory disorders(rheumatoid arthritis),and traumatic injuries(such as stress fractures).[1,2]Clinically,BME primarily manifests as localized pain,often accompanied by joint effusion and warmth near the affected joint.Diagnostic protocols typically include physical examination,serological assays,bone marrow biopsies,dual-energy X-ray absorptiometry(DEXA)scans,magnetic resonance imaging(MRI),and ultrasonography,with computed tomography(CT)scans and radiographs being less effective.

Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.

Combinative approach of transzonular triamcinolonemoxifloxacin and perioperative drops to minimize postoperative complications of cataract surgery

AIM: To investigate the effectiveness of combinationtherapy with transzonular triamcinolone-moxifloxacin andconventional perioperative drops in reducing postoperativecomplications of cataract surgery. METHODS: Electronic medical records of cataractsurgery patients (single surgeon) were reviewed fromJanuary 2018 to September 2021. The rate of postoperativecomplications including prolonged and/or recurrentpostoperative inflammation, endophthalmitis, cystoid macularedema (CME), and intraocular pressure (IOP) was comparedbetween the patients receiving combinative therapy andpatients receiving drops only. RESULTS: Totally 596 patients and 1057 eyes(Combinative-Therapy group 493 and Drop-Only group 564)were included in this study. Using combination therapyreduced the relative risk of postoperative inflammationby 26.9% (16.6% Combinative-Therapy vs 22.7% Drop-Only, P=0.013). The incidence of endophthalmitis was 0in Combinative-Therapy group vs 0.5% in Drop-Only group(relative risk reduction 100%), although not statisticallysignificant (P=0.10). The incidence of severe IOP spikeswas not significantly different between Combinative-Therapy (2.4%) and Drop-Only (1.6%) groups (P=0.33).The relative risk of postoperative CME was 51.4% less inthree months follow up visit in Combinative-Therapy group,although not statistically significant (P=0.07). The visualoutcome 1-month postop. (best corrected visual acuity) wassignificantly better in Combinative-Therapy (logMAR 0.10)compared to Drop-Only (logMAR 0.14) groups (P=0.02) whilethe baseline visual acuity was not significantly different. CONCLUSION: The combinative approach oftranszonular triamcinolone-moxifloxacin plus perioperativeeyedrops is an effective method to minimize postoperativeinflammation, with better visual outcomes. It couldpotentially reduce the risk of postoperative endophthalmitisand CME (near-significant P-values;larger studies couldanalyze better considering low incidence).

Silicone oil as a corneal lubricant to reduce corneal edema and improve visualization during

AIM:To evaluate the efficacy and safety of silicone oil(SO)as a corneal lubricant to improve visualization during vitrectomy.METHODS:Patients who underwent vitreoretinal surgery were divided into two groups.Group 1 was operated on with initial SO(Oxane 5700)as a corneal lubricant.Group 2 was operated on with initial lactated ringer’s solution(LRS)and then replaced with SO as required.Fundus clarity was scored during the surgery.Fluorescein staining was performed to determine the damage to corneal epithelium.RESULTS:Totally 114 eyes of 114 patients were included.Single SO use maintained a clear cornea and provided excellent visualization of surgical image.In group 1,the fundus clarity was grade 3 in 41/45 eyes and grade 2 in 4/45 eyes.In group 2,corneal edema frequently occurred after initial LRS use.The fundus clarity was grade 3 in 19/69 eyes,2 in 37/69 eyes and 1 in 13/69 eyes(P<0.05).SO was applied in 29 eyes of initial LRS use with subsequent corneal edema,which eliminated the corneal edema in 26 eyes.Corneal fluorescein staining score in group 1 was 0 in 28 eyes,1 in 11 eyes and 2 in 6 eyes,and 40,20 and 9,respectively,in group 2(all P>0.05).CONCLUSION:The use of SO as a corneal lubricant is effective and safe for preserving and improving corneal clarity and providing clear surgical field during vitrectomy.

Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Global trends in diabetic eye disease research from 2012 to 2021

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy

AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.

Impact of COVID-19-related lifestyle changes on diabetic macular edema

AIM:To assess diabetic macular edema(DME)progression during the early phases of the COVID-19 pandemic,when severe societal restrictions raised the concern of possible deterioration of health in patients with systemic conditions,particularly those requiring frequent office visits.METHODS:This is a multicenter retrospective chart review of 370 patients(724 eyes)with an established diagnosis of DME seen on 3 separate visits between January 2019 and July 2021.Period 1 was January 2019 to February 2020(considered pre-COVID-19),period 2 was March 2020 to December 2020(considered the height of the pandemic;highest level of pandemic-related clinical and societal regulations)and period 3 was January 2021 to July 2021(re-adjustment to the new“pandemic norms”).Main outcome measures included visual acuity,body mass index(BMI),blood pressure(BP),hemoglobin A1c(HbA1c),macular thickness,patient adherence to scheduled ophthalmology visits,and DME treatment(s)received at each visit.To facilitate measurement of macular thickness,each macula was divided into 9 Early Treatment Diabetic Retinopathy Study(ETDRS)-defined macular sectors as measured by OCT imaging.RESULTS:There was no change of BMI,systolic BP,and diastolic BP between any of the time periods.HbA1c showed a very small increase from period 1(7.6%)to period 2(7.8%,P=0.015)and decreased back to 7.6%at period 3(P=0.12).Macular thickness decreased for 100%of macular regions.The central macular thickness decreased across all 3 periods from 329.5 to 316.6μm(P=0.0045).After analysis of multiple variables including HbA1c,BMI,adherence to scheduled appointments,different clinic centers,and treatment interventions,there was no easily identifiable subgroup of patients that experienced the increase in DME.CONCLUSION:DME doesn’t worsen during the COVID-19 pandemic,instead sustaining a very small but statistically significant improvement.While identifying a mechanism behind our findings is beyond the scope of this study,potential explanations may include a delay in retinal changes beyond our study period,an unexpected increase in treatment frequency despite pandemic restrictions,and an unanticipated pandemic-related improvement in some lifestyle factors that may have had a positive impact on DME.

Retinal vascular morphological characteristics in diabetic retinopathy: an artificial intelligence study using a transfer learning system to analyze ultra-wide field images

AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study.The severity of DR patients was graded as mild,moderate and severe non-proliferative diabetic retinopathy(NPDR)according to the international clinical diabetic retinopathy(ICDR)disease severity scale classification,and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods.The presence of DME was determined by optical coherence tomography(OCT),and differences in vascular morphological characteristics were compared between patients with and without DME.RESULTS:Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99%and a Dice metric of 0.76.Compared with the healthy group,the DR group had smaller vessel angles(33.68±3.01 vs 37.78±1.60),smaller fractal dimension(Df)values(1.33±0.05 vs 1.41±0.03),less vessel density(1.12±0.44 vs 2.09±0.36)and fewer vascular branches(206.1±88.8 vs 396.5±91.3),all P<0.001.As the severity of DR increased,Df values decreased,P=0.031.No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics.CONCLUSION:In this study,an artificial intelligence retinal vessel segmentation system is used with 99%accuracy,thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology.DR patients have a tendency of vascular occlusion and dropout.The presence of DME does not compromise the integral retinal vascular pattern.

Effectiveness of intravitreal ranibizumab for diabetic macular edema in vitrectomized versus non-vitrectomized eyes:a Meta-analysis

AIM:To evaluate the effectiveness and safety of intravitreal ranibizumab(IVR)for diabetic macular edema(DME)in vitrectomized versus non-vitrectomized eyes.METHODS:The PubMed,EMBASE,Web of Science,Cochrane,EBSCO were comprehensively searched for studies comparing vitrectomized and non-vitrectomized eyes with DME.Clinical outcomes of best-corrected visual acuity(BCVA),central macular thickness(CMT),the mean number of intravitreal injection and adverse events were extracted and analyzed.RESULTS:Six studies involving 641 eyes were included.Final visual gain significantly improved and CMT significantly reduced in vitrectomized eyes at 6mo and 12mo visits(P<0.05).Although the mean reduction in CMT among non-vitrectomized eyes was significantly greater than in vitrectomized eyes at the 6mo[mean difference(MD)=53.57,95%confidence interval(CI):28.03 to 78.72,P<0.0001]and 12mo(MD=49.65,95%CI:19.58 to 79.72,P=0.01),no significant difference was detected in improvement in BCVA at either 6mo(MD=0.05,95%CI:-0.02 to 0.13,P=0.14)or 12mo(MD=0.03,95%CI:-0.04 to 0.09,P=0.43).Injection number of ranibizumab in non-vitrectomized eyes was significantly less than that in vitrectomized eyes during 6-month period(MD=0.60,95%CI:0.16 to 1.04,P=0.008),while there was no statistically significant difference between the two groups during 12mo of follow-up.CONCLUSION:Evidence from current study suggests that IVR was useful for both vitrectomized group and nonvitrectomized group with DME.Although less reduction in macular thickness is found in vitrectomized group,visual improvement between two groups is similar.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema:optical coherence tomography and optical coherence tomography angiography

AIM:To analyze the relationship between optical coherence tomography(OCT)and OCT angiography(OCTA)imaging in patients with diabetic macular edema(DME)who are treated with a combination of aflibercept and triamcinolone acetonide(TA).METHODS:A total of 76 eyes newly diagnosed DME were included in this study.They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA.Injections once a month for a total of three injections.Central macular thickness(CMT),number of hyperreflective foci(HRF),height of subretinal fluid(SRF),and area of foveal avascular zone(FAZ)were evaluated using OCT and OCTA at baseline and after each monthly treatment.RESULTS:Both groups showed improvement in best corrected visual acuity(BCVA)and reduction in macular edema after treatment,and the difference in BCVA between the two groups was statistically significant after each treatment(P<0.05).The difference in CMT between the two groups was statistically significant after the first two injections(P<0.01),but not after the third injection(P=0.875).The number of HRF(1mo:7.41±8.25 vs 10.86±7.22,P=0.027;2mo:5.33±6.13 vs 9.12±8.61,P=0.034;3mo:3.58±3.00 vs 6.37±5.97,P=0.007)and height of SRF(1mo:82.39±39.12 vs 105.77±42.26μm,P=0.011;2mo:36.84±10.02 vs 83.59±37.78μm,P<0.01;3mo:11.57±3.29 vs 45.43±12.60μm,P<0.01)in combined group were statistically significant less than aflibercept group after each injection,while the area of FAZ showed no significant change before and after treatment in both groups.CONCLUSION:The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF.However,both aflibercept and combination therapy show no significant change in the area of FAZ.

Clinical characteristics of peripapillary hyperreflective ovoid mass-like structures in myopic children

AIM:To describe the characteristics of peripapillary hyperreflective ovoid mass-like structure(PHOMS)in myopic children and to investigate factors associated with PHOMS.METHODS:This retrospective observational study included 101 eyes of 101 children(age≤17y)with myopia.All included patients underwent comprehensive clinical examination.Optic nerve canal parameters,including disc diameter,optic nerve head(ONH)tilt angle,and border tissue angle were measured using serial enhanced-depth imaging spectral-domain optical coherence tomography(EDI-OCT).Based on the optic disc drusen consortium’s definition of PHOMS,eyes were classified as PHOMS group and non-PHOMS group.PHOMS was categorized according to height.RESULTS:Sixty-seven(66.3%)eyes were found with PHOMS.Small PHOMS could only be detected by optical coherence tomography(OCT).Medium PHOMS could be seen with blurred optic disc borders corresponding to OCT.The most frequent location of PHOMS was at the nasosuperior(91%,61 of 67 eyes)to ONH disc.The axial length and spherical equivalent were more myopic in the PHOMS group than in the non-PHOMS group(both P<0.001).ONH tilt angle was also significantly greater in PHOMS group than in non-PHOMS group[8.90(7.16-10.54)vs 3.93(3.09-5.25),P<0.001].Border tissue angle was significantly smaller in PHOMS group than in non-PHOMS group[29.70(20.90-43.81)vs 45.62(35.18-60.45),P<0.001].In the multivariable analysis,spherical equivalent(OR=3.246,95%CI=1.209-8.718,P=0.019)and ONH tilt angle(OR=3.275,95%CI=1.422-7.542,P=0.005)were significantly correlated with PHOMS.There was no disc diameter associated with PHOMS.In the linear regression analysis,border tissue angle was negatively associated with PHOMS height(β=-2.227,P<0.001).CONCLUSION:PHOMS is associated with optic disc tilt and optic disc nasal shift in myopia.Disc diameter is not a risk factor for PHOMS.The changes in ONH caused by axial elongation facilitated an understanding of the mechanism of PHOMS.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Analysis of risk factors for lymphedema of the lower limbs after endometrial cancer surgery and suggestions for prevention and treatment:Retraction

In the article titled“Analysis of risk factors for lymphedema of the lower limbs after endometrial cancer surgery and suggestions for prevention and treatment”by Zhang Q and Liu L(J Integr Nurs 2021;3(2):67-71.doi:10.4103/jin.jin_13_21),[1]the content and results data of this article was questioned by International database(Web of Science)institution.This article was then investigated by the publisher and Journal of Integrative Nursing(JIN).The investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:(1)Discrepancies in scope;(2)Discrepancies in the description of the research reported;(3)Discrepancies between the availability of data and the research described;(4)Inappropriate citations;(5)Incoherent,meaningless and/or irrelevant content included in the article;(6)The ethical approval by an Institutional Review Board(IRB)committee or equivalent not provided in this article.The editorial office of JIN sent emails many times but received no replies and reasonable explanations from the authors.Therefore,this article is retracted.

Safety and in Vivo Anti-Inflammatory Activity of Ethanolic Extract of Ficus umbellata (Vahl.) Leaves

Toxicity is the totality of adverse effects, which can be functional and morphological lesions in a living organism, caused by a substance introduced in relatively high single doses or in small, repeated doses. The aim of this study was to assess the OECD-recommended acute oral toxicity and anti-inflammatory activity of ethanolic extract of Ficus umbellata leaves. Animals were given a single oral dose of 1000, 3000 and 5000 mg/Kg body weight (BW) of the extract. For the anti-inflammatory activity test, rats were given the ethanolic extract of F. umbellata leaves at doses of 100, 300 and 500 mg/Kg or aspirin® at a concentration of 100 mg/Kg PC orally, one hour before injection of 0.05 ml of 1% formalin under the plantar fascia of the rat’s right hind paw. Paw volume measurements were taken one, two and three hours after formalin injection, using an electronic caliper. After 14 days of observation, no deaths were observed in treated rats. The LD50 of ethanolic extract of Ficus umbellata leaf powder is greater than 5000 mg/Kg body weight. This extract has no significant effects on hematological parameters and on the main markers of nephrotoxicity and hepatotoxicity for a single dose of less than 5000 mg/Kg PC. It reduces formalin-induced edema. Evaluation of the percentage inhibition showed that the extract had greater anti-inflammatory activity at 3 hours after the start of the experiment. However, better inhibition of inflammatory oedema of the paw of rats treated with 500 mg/Kg was observed at 5 hours after the start of the experiment, with a percentage inhibition of 69.23 ± 1.02, compared with the reference group treated with aspirin® 100 mg/Kg, which showed an inhibition of 63.50 ± 0.98. These results show that F. umbellata leaves possess anti-inflammatory activity, which would justify their use in traditional African medicine to prevent or treat inflammation.

Diabetic retinopathy:A review on its pathophysiology and novel treatment modalities

Diabetes mellitus(DM)is a chronic metabolic non-communicable disease with the ability to cause serious microvascular and macrovascular complications throughout the body,including in the eye.Diabetic retinopathy(DR),present in onethird of patients with diabetes,is a vision-threatening complication caused by uncontrolled diabetes,which greatly affects the retinal blood vessels and the lightsensitive inner retina,eventually leading to blindness.Several epidemiological studies elucidate that DR can vary by age of onset,duration,types of diabetes,and ethnicity.Recent studies show that the pathogenesis of diabetic retinopathy has spread its roots beyond merely being the result of hyperglycemia.The complexity of its etiopathology and diagnosis makes therapeutic intervention challenging.This review throws light on the pathological processes behind DR,the cascade of events that follow it,as well as the available and emerging treatment options.

Progress in the Treatment of DME

Diabetic macular edema (DME) is a common ocular complication of diabetes mellitus (DM) and an important cause of vision loss. The pathogenesis of DME is complex and can occur at any time of diabetic retinopathy (DR). Effective methods of treating DME are essential to prevent irreversible damage to visual function. To date, laser photocoagulation, vascular endothelial growth factor (VEGF) inhibitors, and corticosteroids have demonstrated their therapeutic efficacy in large randomized controlled trials and real-life observational studies. Clinicians need to consider various factors, such as efficacy, safety, accessibility, and cost, in the selection of various options. This review summarizes the current therapeutic approaches for DME to provide new references for the treatment of DM.

Comparison of efficacy of lung ultrasound and chest X-ray in diagnosing pulmonary edema and pleural effusion in ICU patients: A single centre, prospective, observational study

Background and Aims While chest X-ray (CXR) has been a conventional tool in intensive care units (ICUs) to identify lung pathologies, computed tomography (CT) scan remains the gold standard. Use of lung ultrasound (LUS) in resource-rich ICUs is still under investigation. The present study compares the utility of LUS to that of CXR in identifying pulmonary edema and pleural effusion in ICU patients. In addition, consolidation and pneumothorax were analyzed as secondary outcome measures. Material and Methods This is a prospective, single centric, observational study. Patients admitted in ICU were examined for lung pathologies, using LUS by a trained intensivist;and CXR done within 4 hours of each other. The final diagnosis was ascertained by an independent senior radiologist, based on the complete medical chart including clinical findings and the results of thoracic CT, if available. The results were compared and analyzed. Results Sensitivity, specificity and diagnostic accuracy of LUS was 95%, 94.4%, 94.67% for pleural effusion;and 98.33%, 97.78%, 98.00% for pulmonary edema respectively. Corresponding values with CXR were 48.33%, 76.67%, 65.33% for pleural effusion;and 36.67%, 82.22% and 64.00% for pulmonary edema respectively. Sensitivity, specificity and diagnostic accuracy of LUS was 91.30%, 96.85%, 96.00% for consolidation;and 100.00%, 79.02%, 80.00% for pneumothorax respectively. Corresponding values with CXR were 60.87%, 81.10%, 78.00% for consolidation;and 71.3%, 97.20%, 96.00% for pneumothorax respectively. Conclusion LUS has better diagnostic accuracy in diagnosis of pleural effusion and pulmonary edema when compared with CXR and is thus recommended as an effective alternative for diagnosis of these conditions in acute care settings. Our study recommends that a thoracic CT scan can be avoided in most of such cases.

Knockout of Sirt2 alleviates traumatic brain injury in mice

Sirtuin 2(SIRT2)inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI)remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of the effector caspase-1,reduced neuroinflammation and neuronal pyroptosis,and improved neurological function.Knoc kout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis.Our findings suggest that knockout of Sirt2 is neuro protective against TBI;therefore.Sirt2 could be a novel to rget for TBI treatment.