AIM:To explore the brain mechanism of acupuncture for children with anisometropic amblyopia using the voxelmirror homotopic connectivity(VMHC)analysis method of resting functional magnetic resonance imaging(rs-fMRI)te...AIM:To explore the brain mechanism of acupuncture for children with anisometropic amblyopia using the voxelmirror homotopic connectivity(VMHC)analysis method of resting functional magnetic resonance imaging(rs-fMRI)technology based on clinical effectiveness.METHODS:Eighty children with anisometropic monocular amblyopia were randomly divided into two groups:control(40 cases,1 case of shedding)and acupuncture(40 cases,1 case of shedding)groups.The control group was treated with glasses,red flash,grating,and visual stimulations,with each procedure conducted for 5min per time.Based on routine treatment,the acupuncture group underwent acupuncture of“regulating qi and unblocking meridians to bright eyes”,Jingming(BL1),Cuanzhu(BL2),Guangming(GB37),Fengchi(GB20)acupoints were taken on both sides,with the needle kept for 30min each time.Both groups were treated once every other day,three times per week,for a total of 4wk.After the treatment,the overall curative effect of the two groups and the latency and amplitude changes of P100 wave of pattern visual-evoked potential were counted.At the same time,nine children with left eye amblyopia were randomly selected from the two groups and were scanned with rsfMRI before and after treatment.The differences in the brain regions between the two groups were compared and analyzed with VMHC.RESULTS:Chi-square test showed a notable difference in the total efficiency rate between the acupuncture(94.87%)and control groups(79.49%).Regarding the P100 wave latency and amplitude,the acupuncture group had significantly shorter latency and higher amplitude of P100 wave than the control group.Moreover,the VMHC values of the bilateral temporal lobe,superior temporal gyrus,and middle temporal gyrus were notably increased in the acupuncture group after treatment.CONCLUSION:Acupuncture combined with conventional treatment can significantly improve the corrected visual acuity and optic nerve conduction in children with anisometropic amblyopia.Compared with the conventional treatment,the regulation of acupuncture on the functional activities of the relevant brain areas in the anterior cerebellum may be an effective acupuncture mechanism for anisometropic amblyopia.展开更多
AIM:To compare the retinal nerve fiber layer (RNFL) thickness and macular thickness in the amblyopic eye with that in the sound eye of children with hyperopic anisometropic amblyopia using optical coherence tomography...AIM:To compare the retinal nerve fiber layer (RNFL) thickness and macular thickness in the amblyopic eye with that in the sound eye of children with hyperopic anisometropic amblyopia using optical coherence tomography (OCT). METHODS:A prospective, nonrandom, intraindividual comparative cohort study includes 72 children with hyperopic anisometropic amblyopia in a single center. Macular thickness, macular foveola thickness, and peripapillary RNFL thickness were compared between the amblyopia eyes and the contralateral sound eyes. ·RESULTS:There were 38 male and 34 female patients, with a mean age as 9.7 ±1.9 years (range, 5-16 years). Hyperopic was +3.62±1.16D (range +2.00D to +6.50D) in the amblyopic eyes, which was significantly higher in the control eyes with +0.76±0.90D (range 0D to +2.00D) (P 【 0.01). The mean peripapillary RNFL thickness was 113.9± 7.2μm and 109.2 ±6.9μm in the amblyopic eye and the normal eye, respectively, reaching statistical significance (P = 0.02). The mean macular foveola thickness was significantly thicker in the amblyopic eyes than the contralateral sound eyes (181.4±14.2μm vs 175.2±13.3μm, P 【0.01), but the 1mm, 3mm or 6mm macular thickness central macular thickness was not significantly different. Degree of anisometropia in the contralateral eyes was not significantly correlated with differences of peripapillary RNFL, macular foveola thickness or central macular thickness. CONCLUSION:Eyes with hyperopic anisometropic amblyopia are found thicker macular foveola and peripapillary RNFL than the contralateral eyes in children.展开更多
AIM: To evaluate the effects of femtosecond laser-assisted in situ keratomileusis(FS-LASIK) and small-incision lenticule extraction(SMILE) to correct high myopic anisometropic amblyopia in juvenile patients. METH...AIM: To evaluate the effects of femtosecond laser-assisted in situ keratomileusis(FS-LASIK) and small-incision lenticule extraction(SMILE) to correct high myopic anisometropic amblyopia in juvenile patients. METHODS: From November 2013 to January 2015, 33 amblyopic patients with high myopic anisometropic amblyopia were studied. FS-LASIK(30 eyes) or SMILE(3 eyes) was performed in the amblyopic eyes. Visual acuity, refraction, contrast sensitivity, stereoacuity and complications were evaluated. Patients completed followup examinations at 3 d, 1 mo, 3 mo and the last follow-up time(mean 8.17±3.23 mo) after surgery. RESULTS: The mean age at surgery was 9.04±3.04 y(range 6-16 y). The mean spherical equivalent in the amblyopic eyes was significantly decreased from-10.00±2.39 D preoperatively to-0.06±1.06 D at 1 mo,-0.19±1.33 D at 3 mo and-0.60±1.43 D at approximately 8 mo postoperatively(P〈0.05 for all). The mean myopic anisometropia was significantly decreased from-9.45±2.33 D preoperatively to +0.37±1.48 D at 1 mo,-0.46±1.47 D at 3 mo and-0.09±1.83 D at approximately 8 mo(P〈0.05 for all). The logarithm of the minimum angle of resolution(log MAR) for uncorrected and corrected distance visual acuity(UDVA and CDVA, respectively) of the amblyopic eye improved from 1.74±0.35 and 0.98±0.63 preoperatively to 0.45±0.31 and 0.41±0.33 at approximately 8 mo after surgery, respectively. The logM AR CDVA at 3 d, 1, 3 and 8 mo postoperatively improved by means of 1.42, 2.22, 2.96, and 4.39 lines, and a gain of more than two lines accounted for 45%, 50%, 74% and 86% of all patients, respectively. The contrast sensitivity of both amblyopic eyes and dominant eyes at 0.5, 2, 8 cycles perdegree was significantly improved postoperatively(P〈0.05 for all). Of the 33 pediatric patients, no patients had near stereopsis preoperatively and seven patients(21.2%) recovered near stereopsis(400″ to 60″) at approximately 8 mo after surgery. No intraoperative or postoperative complications occurred in any patient.CONCLUSION: FS-LASIK or SMILE can be promising alternative methods to correct high myopic anisometropic amblyopia in juvenile patients who have failed with traditional approaches.展开更多
Dear Editor,We read with great interest article titled'Anisometropia magnitude and visual deficits in previously untreated anisometropic amblyopia'by Chen et al[1].The authors have analysed subjects with previ...Dear Editor,We read with great interest article titled'Anisometropia magnitude and visual deficits in previously untreated anisometropic amblyopia'by Chen et al[1].The authors have analysed subjects with previously untreated anisometropic amblyopia and found a significant correlation between high degree of anisometropia and deep amblyopia,worse contrast sensitivity,fusion and stereopsis functions.We commend the authors in addressing a very important problem and agree with the authors in the notation that children with anisometropia are usually detected later owing to lack of noticeable physical abnormalities.展开更多
Dear Sir,I am Dr. Huijae Lee, from the Seoul Ire Eye Clinic,Seoul, Korea. I write to present a case report of esotropia after occlusion therapy.Amblyopia can be caused by
Amblyopia is a neurodevelopmental disorder of the visual cortex arising from abnormal visual experience early in life. Amblyopia is a major cause of impaired vision in infants and young children (prevalence around 3.5...Amblyopia is a neurodevelopmental disorder of the visual cortex arising from abnormal visual experience early in life. Amblyopia is a major cause of impaired vision in infants and young children (prevalence around 3.5%). There are different treatment options for amblyopia based on its severity and age of the patient. Traditional treatments include patching or occlusion of the dominant eye and pharmacological penalisation using Atropine (1%). Recent developments in amblyopia management have found success with the use of binocular exercises and certain modifications of glasses and contact lenses. The critical age up to which amblyopia is treatable or reversible is also being pushed up with more research. With newer advancements in amblyopia therapy, the success rate is also improving with multimodal approach.展开更多
Objective:To evaluate the effect of acupuncture on anisometropic amblyopia(AA)and explore its potential mechanism for children with AA.Methods:Seventy-six children with monocular AA were randomized into a conventional...Objective:To evaluate the effect of acupuncture on anisometropic amblyopia(AA)and explore its potential mechanism for children with AA.Methods:Seventy-six children with monocular AA were randomized into a conventional treatment group and a combined treatment group of acupuncture and conventional treatment,with 38 patients in each group.In the conventional treatment group,on the base of patching regimen,the red flashing,grating and visual stimulation were delivered.Each approach lasted for 5 min per session and was given once every two days,three times a week,for 4 consecutive weeks.In the acupuncture-combined treatment group,on the base of the regimen of conventional treatment group,acupuncture was applied to Jingming(BL1),Cuanzhu(BL2),Fengchi(GB20)and Guangming(GB37),with needles retained for 20 min per session,once every two days,three times of intervention a week and for 4 consecutive weeks.Before and after treatment,the best corrected vision acuity(BCVA)was observed to evaluate the clinical effect in the two groups.Before treatment started,15 patients with AA on left side were randomized selected from each group and the resting-state functional magnetic resonance imaging(rs-fMRI)was operated before and after treatment.Simultaneously,eight healthy children with normal visual acuity were recruited to be the normal control group and received one-time rs-fMRI scanning.Based on the activation likelihood estimation(ALE),the visual"what"pathway network was constructed.By analyzing the amplitude of low frequency fluctuation(ALFF)and the regional homogeneity(ReHo),the differences in the regional autonomous function activities in the key brain areas of the"what"pathway were compared among the three groups.Results:(1)Clinical effect:After treatment,BCVA was(0.6[0.5,0.6]),higher than that(0.4[0.3,0.5])before treatment,presenting the statistical difference(P<0.05)in the conventional treatment group.BCVA was(0.6[0.6,0.8]),higher than that(0.4[0.4,0.5])before treatment,presenting the statistical difference(P<0.05)in the acupuncture-combined treatment group.BCVA in the acupuncture-combined treatment group was higher than that of the conventional treatment group(P<0.05)after treatment.The total effective rate was 86.1%in the acupuncture-combined treatment group,higher than that(65.8%)of the conventional treatment group(P<0.05).(2)Mechanism:(1)ALFF:In comparison with the healthy control group,the ALFF in the primary visual cortex of the"what"pathway for AA children was reduced significantly(P<0.05),and ALFF in the right fusiform gyrus and the right inferior temporal gyrus increased significantly when compared with the healthy children(P<0.05).Compared with that before treatment,there was no significant difference in the brain areas of the"what"pathway after treatment in the conventional treatment group(P>0.05).In the acupuncture-combined treatment group,ALFF in the right inferior occipital gyrus and the right fusiform gyrus of the"what"pathway increased after treatment when compared with that before treatment(P<0.05).After treatment,in comparison with the conventional treatment group,there was no significant difference in the brain areas of"what"pathway in the acupuncture-combined treatment group(P>0.05).(2)ReHo:ReHo in the right inferior occipital gyrus,the right fusiform gyrus and the right inferior temporal gyrus in the"what"pathway was elevated significantly in AA children when compared with that in the healthy control group(P<0.05).ReHo of the left inferior occipital gyrus and the left fusiform gyrus increased significantly after treatment when compared with that before treatment in the conventional treatment group(P<0.05).ReHo of the right inferior occipital gyrus,the left and the right fusiform gyrus increased significantly after treatment when compared with that before treatment in the acupuncture-combined treatment group(P<0.05).After treatment,ReHo of the right inferior temporal gyrus in the"what"pathway in the acupuncture-combined treatment group was significantly higher than that of the conventional treatment group(P<0.05).Conclusion:The acupuncture combined with conventional treatment improves BCVA and the total effective rate of AA children.The changes in the regional function activity of the brain areas within the"what"pathway were dominated by the compensatory increase of the autonomous activity in the occipital lobe(inferior occipital gyrus)and the temporal lobe(inferior temporal gyrus)in AA children.Both conventional treatment and acupuncture can enhance the intensity of autonomous function activities in the occipital lobe(inferior occipital gyrus)and the temporal lobe(fusiform gyrus/inferior temporal gyrus)in the"what"pathway so as to relieve visual impairment.ReHo in the inferior temporal gyrus in the acupuncture-combined treatment group was higher than that of the conventional treatment group and it suggests that the inferior temporal gyrus may be the key brain area to the improvement of visual function in the"what"pathway.展开更多
基金Supported by National Natural Science Foundation of China(No.82160935,No.82260965)Traditional Chinese Medicine Discipline“Qi Huang Ying Cai”Tutor Special Fund Doctoral Program(No.ZYXKBD-202208)+4 种基金Higher Education Innovation Fund Project of Gansu Province(No.2021A-087)Natural Science Foundation of Gansu Province(No.22JR5RA583)Traditional Chinese Medicine Discipline“Qi Huang Ying Cai”Tutor Special Fund Master’s Supervisor Program(No.ZYXKSD-202220)Youth Research Fund Project of Gansu University of Chinese Medicine(No.ZQ2017-9)Gansu Province 2023 Provincial Key Talent Project(No.2).
文摘AIM:To explore the brain mechanism of acupuncture for children with anisometropic amblyopia using the voxelmirror homotopic connectivity(VMHC)analysis method of resting functional magnetic resonance imaging(rs-fMRI)technology based on clinical effectiveness.METHODS:Eighty children with anisometropic monocular amblyopia were randomly divided into two groups:control(40 cases,1 case of shedding)and acupuncture(40 cases,1 case of shedding)groups.The control group was treated with glasses,red flash,grating,and visual stimulations,with each procedure conducted for 5min per time.Based on routine treatment,the acupuncture group underwent acupuncture of“regulating qi and unblocking meridians to bright eyes”,Jingming(BL1),Cuanzhu(BL2),Guangming(GB37),Fengchi(GB20)acupoints were taken on both sides,with the needle kept for 30min each time.Both groups were treated once every other day,three times per week,for a total of 4wk.After the treatment,the overall curative effect of the two groups and the latency and amplitude changes of P100 wave of pattern visual-evoked potential were counted.At the same time,nine children with left eye amblyopia were randomly selected from the two groups and were scanned with rsfMRI before and after treatment.The differences in the brain regions between the two groups were compared and analyzed with VMHC.RESULTS:Chi-square test showed a notable difference in the total efficiency rate between the acupuncture(94.87%)and control groups(79.49%).Regarding the P100 wave latency and amplitude,the acupuncture group had significantly shorter latency and higher amplitude of P100 wave than the control group.Moreover,the VMHC values of the bilateral temporal lobe,superior temporal gyrus,and middle temporal gyrus were notably increased in the acupuncture group after treatment.CONCLUSION:Acupuncture combined with conventional treatment can significantly improve the corrected visual acuity and optic nerve conduction in children with anisometropic amblyopia.Compared with the conventional treatment,the regulation of acupuncture on the functional activities of the relevant brain areas in the anterior cerebellum may be an effective acupuncture mechanism for anisometropic amblyopia.
文摘AIM:To compare the retinal nerve fiber layer (RNFL) thickness and macular thickness in the amblyopic eye with that in the sound eye of children with hyperopic anisometropic amblyopia using optical coherence tomography (OCT). METHODS:A prospective, nonrandom, intraindividual comparative cohort study includes 72 children with hyperopic anisometropic amblyopia in a single center. Macular thickness, macular foveola thickness, and peripapillary RNFL thickness were compared between the amblyopia eyes and the contralateral sound eyes. ·RESULTS:There were 38 male and 34 female patients, with a mean age as 9.7 ±1.9 years (range, 5-16 years). Hyperopic was +3.62±1.16D (range +2.00D to +6.50D) in the amblyopic eyes, which was significantly higher in the control eyes with +0.76±0.90D (range 0D to +2.00D) (P 【 0.01). The mean peripapillary RNFL thickness was 113.9± 7.2μm and 109.2 ±6.9μm in the amblyopic eye and the normal eye, respectively, reaching statistical significance (P = 0.02). The mean macular foveola thickness was significantly thicker in the amblyopic eyes than the contralateral sound eyes (181.4±14.2μm vs 175.2±13.3μm, P 【0.01), but the 1mm, 3mm or 6mm macular thickness central macular thickness was not significantly different. Degree of anisometropia in the contralateral eyes was not significantly correlated with differences of peripapillary RNFL, macular foveola thickness or central macular thickness. CONCLUSION:Eyes with hyperopic anisometropic amblyopia are found thicker macular foveola and peripapillary RNFL than the contralateral eyes in children.
基金Supported by the National Natural Science Foundation (No.81470626)
文摘AIM: To evaluate the effects of femtosecond laser-assisted in situ keratomileusis(FS-LASIK) and small-incision lenticule extraction(SMILE) to correct high myopic anisometropic amblyopia in juvenile patients. METHODS: From November 2013 to January 2015, 33 amblyopic patients with high myopic anisometropic amblyopia were studied. FS-LASIK(30 eyes) or SMILE(3 eyes) was performed in the amblyopic eyes. Visual acuity, refraction, contrast sensitivity, stereoacuity and complications were evaluated. Patients completed followup examinations at 3 d, 1 mo, 3 mo and the last follow-up time(mean 8.17±3.23 mo) after surgery. RESULTS: The mean age at surgery was 9.04±3.04 y(range 6-16 y). The mean spherical equivalent in the amblyopic eyes was significantly decreased from-10.00±2.39 D preoperatively to-0.06±1.06 D at 1 mo,-0.19±1.33 D at 3 mo and-0.60±1.43 D at approximately 8 mo postoperatively(P〈0.05 for all). The mean myopic anisometropia was significantly decreased from-9.45±2.33 D preoperatively to +0.37±1.48 D at 1 mo,-0.46±1.47 D at 3 mo and-0.09±1.83 D at approximately 8 mo(P〈0.05 for all). The logarithm of the minimum angle of resolution(log MAR) for uncorrected and corrected distance visual acuity(UDVA and CDVA, respectively) of the amblyopic eye improved from 1.74±0.35 and 0.98±0.63 preoperatively to 0.45±0.31 and 0.41±0.33 at approximately 8 mo after surgery, respectively. The logM AR CDVA at 3 d, 1, 3 and 8 mo postoperatively improved by means of 1.42, 2.22, 2.96, and 4.39 lines, and a gain of more than two lines accounted for 45%, 50%, 74% and 86% of all patients, respectively. The contrast sensitivity of both amblyopic eyes and dominant eyes at 0.5, 2, 8 cycles perdegree was significantly improved postoperatively(P〈0.05 for all). Of the 33 pediatric patients, no patients had near stereopsis preoperatively and seven patients(21.2%) recovered near stereopsis(400″ to 60″) at approximately 8 mo after surgery. No intraoperative or postoperative complications occurred in any patient.CONCLUSION: FS-LASIK or SMILE can be promising alternative methods to correct high myopic anisometropic amblyopia in juvenile patients who have failed with traditional approaches.
文摘Dear Editor,We read with great interest article titled'Anisometropia magnitude and visual deficits in previously untreated anisometropic amblyopia'by Chen et al[1].The authors have analysed subjects with previously untreated anisometropic amblyopia and found a significant correlation between high degree of anisometropia and deep amblyopia,worse contrast sensitivity,fusion and stereopsis functions.We commend the authors in addressing a very important problem and agree with the authors in the notation that children with anisometropia are usually detected later owing to lack of noticeable physical abnormalities.
文摘Dear Sir,I am Dr. Huijae Lee, from the Seoul Ire Eye Clinic,Seoul, Korea. I write to present a case report of esotropia after occlusion therapy.Amblyopia can be caused by
文摘Amblyopia is a neurodevelopmental disorder of the visual cortex arising from abnormal visual experience early in life. Amblyopia is a major cause of impaired vision in infants and young children (prevalence around 3.5%). There are different treatment options for amblyopia based on its severity and age of the patient. Traditional treatments include patching or occlusion of the dominant eye and pharmacological penalisation using Atropine (1%). Recent developments in amblyopia management have found success with the use of binocular exercises and certain modifications of glasses and contact lenses. The critical age up to which amblyopia is treatable or reversible is also being pushed up with more research. With newer advancements in amblyopia therapy, the success rate is also improving with multimodal approach.
基金Supported by Provincial Key Talent Project of Gansu Province:[2023]20National Natural Science Foundation of China:82160935,81860879+2 种基金2022 Doctoral Tutor Project of Chinese Medicine First Level Discipline"Qi Huang Ying Cai"Tutor Special Fund:ZYXKBD-2022082021 Gansu Province Higher Education Innovation Fund Project:2021A-087Gansu University of Traditional Chinese Medicine Science Research and Innovation Fund Project:2022KCYB-8。
文摘Objective:To evaluate the effect of acupuncture on anisometropic amblyopia(AA)and explore its potential mechanism for children with AA.Methods:Seventy-six children with monocular AA were randomized into a conventional treatment group and a combined treatment group of acupuncture and conventional treatment,with 38 patients in each group.In the conventional treatment group,on the base of patching regimen,the red flashing,grating and visual stimulation were delivered.Each approach lasted for 5 min per session and was given once every two days,three times a week,for 4 consecutive weeks.In the acupuncture-combined treatment group,on the base of the regimen of conventional treatment group,acupuncture was applied to Jingming(BL1),Cuanzhu(BL2),Fengchi(GB20)and Guangming(GB37),with needles retained for 20 min per session,once every two days,three times of intervention a week and for 4 consecutive weeks.Before and after treatment,the best corrected vision acuity(BCVA)was observed to evaluate the clinical effect in the two groups.Before treatment started,15 patients with AA on left side were randomized selected from each group and the resting-state functional magnetic resonance imaging(rs-fMRI)was operated before and after treatment.Simultaneously,eight healthy children with normal visual acuity were recruited to be the normal control group and received one-time rs-fMRI scanning.Based on the activation likelihood estimation(ALE),the visual"what"pathway network was constructed.By analyzing the amplitude of low frequency fluctuation(ALFF)and the regional homogeneity(ReHo),the differences in the regional autonomous function activities in the key brain areas of the"what"pathway were compared among the three groups.Results:(1)Clinical effect:After treatment,BCVA was(0.6[0.5,0.6]),higher than that(0.4[0.3,0.5])before treatment,presenting the statistical difference(P<0.05)in the conventional treatment group.BCVA was(0.6[0.6,0.8]),higher than that(0.4[0.4,0.5])before treatment,presenting the statistical difference(P<0.05)in the acupuncture-combined treatment group.BCVA in the acupuncture-combined treatment group was higher than that of the conventional treatment group(P<0.05)after treatment.The total effective rate was 86.1%in the acupuncture-combined treatment group,higher than that(65.8%)of the conventional treatment group(P<0.05).(2)Mechanism:(1)ALFF:In comparison with the healthy control group,the ALFF in the primary visual cortex of the"what"pathway for AA children was reduced significantly(P<0.05),and ALFF in the right fusiform gyrus and the right inferior temporal gyrus increased significantly when compared with the healthy children(P<0.05).Compared with that before treatment,there was no significant difference in the brain areas of the"what"pathway after treatment in the conventional treatment group(P>0.05).In the acupuncture-combined treatment group,ALFF in the right inferior occipital gyrus and the right fusiform gyrus of the"what"pathway increased after treatment when compared with that before treatment(P<0.05).After treatment,in comparison with the conventional treatment group,there was no significant difference in the brain areas of"what"pathway in the acupuncture-combined treatment group(P>0.05).(2)ReHo:ReHo in the right inferior occipital gyrus,the right fusiform gyrus and the right inferior temporal gyrus in the"what"pathway was elevated significantly in AA children when compared with that in the healthy control group(P<0.05).ReHo of the left inferior occipital gyrus and the left fusiform gyrus increased significantly after treatment when compared with that before treatment in the conventional treatment group(P<0.05).ReHo of the right inferior occipital gyrus,the left and the right fusiform gyrus increased significantly after treatment when compared with that before treatment in the acupuncture-combined treatment group(P<0.05).After treatment,ReHo of the right inferior temporal gyrus in the"what"pathway in the acupuncture-combined treatment group was significantly higher than that of the conventional treatment group(P<0.05).Conclusion:The acupuncture combined with conventional treatment improves BCVA and the total effective rate of AA children.The changes in the regional function activity of the brain areas within the"what"pathway were dominated by the compensatory increase of the autonomous activity in the occipital lobe(inferior occipital gyrus)and the temporal lobe(inferior temporal gyrus)in AA children.Both conventional treatment and acupuncture can enhance the intensity of autonomous function activities in the occipital lobe(inferior occipital gyrus)and the temporal lobe(fusiform gyrus/inferior temporal gyrus)in the"what"pathway so as to relieve visual impairment.ReHo in the inferior temporal gyrus in the acupuncture-combined treatment group was higher than that of the conventional treatment group and it suggests that the inferior temporal gyrus may be the key brain area to the improvement of visual function in the"what"pathway.