The relationship between gut microbiota and depressive disorder has become a research focus in recent years. Within the microbiota-gut-brain axis, the gut microbiota influences the onset and progression of depressive disorder primarily through the tryptophan metabolic pathway. Tryptophan, an essential amino acid in humans, is subject to dual regulation by intestinal microorganisms, which modulate its metabolic balance via inflammatory stimulation and microbial metabolite production. In depression, excessive activation of the kynurenine branch of tryptophan metabolism leads to the accumulation of proinflammatory and neurotoxic metabolites, thereby exacerbating neuroinflammation in the brain. Intervention studies indicate that the antidepressant-like effects of probiotics and traditional Chinese medicine are associated with remodeling of the gut microbiota, restoration of tryptophan metabolic balance, and alleviation of neuroinflammation. Furthermore, targeted inhibition of kynurenine 3-monooxygenase can mitigate neuroinflammation by regulating microglial activity, thus improving depressive-like behaviors. In summary, the metabolite-inflammation axis represents a central node in the interaction regulation between tryptophan metabolism and the microbiota-gut-brain axis. This provides a theoretical foundation for developing novel therapeutic strategies targeting depression through modulation of gut microbiota-mediated tryptophan metabolism.
Tryptophan/metabolism* ; Gastrointestinal Microbiome/physiology* ; Humans ; Depressive Disorder/microbiology* ; Probiotics/therapeutic use* ; Brain/metabolism* ; Kynurenine/metabolism* ; Metabolic Networks and Pathways ; Animals ; Medicine, Chinese Traditional

Objective To compare the differences between swept-source optical coherence tomography angiography(SS-OCTA)and ultra-wide-field fluorescein angiography(UWFA)in detecting non-perfusion areas(NPs)in patients with diabetic retinopathy(DR),to evaluate the accuracy of SS-OCTA in predicting NPs outside its visible range,and to explore the distribution patterns of NPs.Methods A retrospective analysis was made on 69 DR patients(88 eyes)who under-went both UWFA and SS-OCTA examinations at the Ophthalmology Department of Sichuan Provincial People's Hospital from December 2022 to September 2024.Manual NP labeling was conducted to compare the detection rate of NPs between the two imaging techniques.The distribution patterns of NPs and the accuracy of SS-OCTA for predicting NPs outside its visible range were also analyzed.Results In a scanning area of 20 mm x 24 mm,the overall NP detection rate by SS-OCTA was 47.40％,with UWFA taken as the standard.The NP detection rate by SS-OCTA was 51.56％in the superotemporal quad-rant,58.35％in the inferotemporal quadrant,45.50％in the superonasal quadrant,and 43.17％in the inferonasal quad-rant.Most NPs occurred in the inferonasal quadrant,accounting for 41.71％of the total NP.The accuracy of SS-OCTA in predicting NPs was 75.00％in the superonasal quadrant and 78.41％in the inferonasal quadrant.The ischemic indices(ISI)of the two imaging techniques were highly positively correlated(r2=0.74).Conclusion Although SS-OCTA can-not yet fully replace UWFA for NP detection in DR patients due to a small visible range,it is still an effective tool to assess retinal ischemia.SS-OCTA has the ability to predict NPs outside its visible range in its scanning range.The inferonasal quadrant is the region where NPs occur most frequently in DR patients,so it is suggested that special attention should be paid to this region in early diagnosis and follow-up periods.

Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

Objective Deep learning provides strong technical support for early diagnosis,lesion segmentation,and treatment prediction of retinal diseases,significantly improving the efficiency and accuracy of diagnosis.But it also faces challenges in terms of different applicability and performance differences of the model,mainly due to the differences in fea-ture extraction ability,computational complexity,and clinical adaptability among different network structures,which make them have different advantages and limitations in different application scenarios.By systematically searching relevant litera-ture in PubMed and Web of Science databases over the past 5 years,this article summarizes the most commonly used deep learning network architectures in common vitreoretinal diseases,summarizes their different advantages and limitations,and analyzes the best application directions of each architecture in the field of ophthalmology,providing reference and inspira-tion for future research.

Objective To compare the differences between swept-source optical coherence tomography angiography(SS-OCTA)and ultra-wide-field fluorescein angiography(UWFA)in detecting non-perfusion areas(NPs)in patients with diabetic retinopathy(DR),to evaluate the accuracy of SS-OCTA in predicting NPs outside its visible range,and to explore the distribution patterns of NPs.Methods A retrospective analysis was made on 69 DR patients(88 eyes)who under-went both UWFA and SS-OCTA examinations at the Ophthalmology Department of Sichuan Provincial People's Hospital from December 2022 to September 2024.Manual NP labeling was conducted to compare the detection rate of NPs between the two imaging techniques.The distribution patterns of NPs and the accuracy of SS-OCTA for predicting NPs outside its visible range were also analyzed.Results In a scanning area of 20 mm x 24 mm,the overall NP detection rate by SS-OCTA was 47.40％,with UWFA taken as the standard.The NP detection rate by SS-OCTA was 51.56％in the superotemporal quad-rant,58.35％in the inferotemporal quadrant,45.50％in the superonasal quadrant,and 43.17％in the inferonasal quad-rant.Most NPs occurred in the inferonasal quadrant,accounting for 41.71％of the total NP.The accuracy of SS-OCTA in predicting NPs was 75.00％in the superonasal quadrant and 78.41％in the inferonasal quadrant.The ischemic indices(ISI)of the two imaging techniques were highly positively correlated(r2=0.74).Conclusion Although SS-OCTA can-not yet fully replace UWFA for NP detection in DR patients due to a small visible range,it is still an effective tool to assess retinal ischemia.SS-OCTA has the ability to predict NPs outside its visible range in its scanning range.The inferonasal quadrant is the region where NPs occur most frequently in DR patients,so it is suggested that special attention should be paid to this region in early diagnosis and follow-up periods.

Objective Deep learning provides strong technical support for early diagnosis,lesion segmentation,and treatment prediction of retinal diseases,significantly improving the efficiency and accuracy of diagnosis.But it also faces challenges in terms of different applicability and performance differences of the model,mainly due to the differences in fea-ture extraction ability,computational complexity,and clinical adaptability among different network structures,which make them have different advantages and limitations in different application scenarios.By systematically searching relevant litera-ture in PubMed and Web of Science databases over the past 5 years,this article summarizes the most commonly used deep learning network architectures in common vitreoretinal diseases,summarizes their different advantages and limitations,and analyzes the best application directions of each architecture in the field of ophthalmology,providing reference and inspira-tion for future research.

Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

Objective To investigate regional spontaneous brain activity in mild cognition impairment (MCI) patients with amnesic (aMCI) and non-amnesic (naMCI).Methods Twenty-five aMCI patients,21 naMCI patients and 15 normal controls (NC) underwent resting-state functional magnetic resonance imaging.The regional homogeneity (ReHo) map of the whole brain was obtained by calculating the similarity of each voxel with its nearest 26 voxel time series.The differences of ReHo map across the whole brain among three groups were compared.Results In aMCI group,ReHo values were lower in right frontal lobe and higher in left middle temporal gyrus and left cerebellum compared with NC (P＜0.05,Alphasim correction).In naMCI group,ReHo values were higher in anterior cingulate cortex and right middle frontal gyrus and lower in right parahippocampa gyrus,right middle temporal gyrus as well as right precuneus compared with NC (P＜0.05,Alphasim correction).Compared with naMCI,the ReHo values were significantly higher in left prefrontal gyrus,left middle temporal gyrus and lower in right cerebellum (P＜0.05,Alphasim correction).Conclusion There are differences in spontaneous brain activity of left prefrontal gyrus,left middle temporal gyrus and right cerebellum between aMCI and naMCI,which may be used to differentiate brain function between aMCI and naMCI patients.

Objective To investigate the characteristics of cognitive impairment and psychotic symptoms in general paresis of insane (GPI) before and after penicillin therapy, and explore factors that may predict the clinical outcomes. Methods Thirty patients with GPI were recruited. All GPI patients underwent a comprehensive neuropsychological assessment before receiving penicillin therapy, and returned for follow-up visits after 7 months. The severity of dementia was determined by Clinical Dementia Rating Scale (CDR), cognitive functions were assessed by Mini Mental State Examination (MMSE) and Alzheimer 's Disease Assessment Scale-cognitive subscale (ADAS-Cog), ability of daily living was assessed by Instrumental Activities of Daily Living Scale (IALD) and Physical Self maintenance Scale(PSMS), behavioral and psychological symptoms were assessed by Neuropsychiatric Inventory (NPI). Aqueous crystalline penicillin G 24 million units per day was administered as continuous infusion for 14 days, followed by benzathine penicillin 2.4 million units IM once per week for 3 weeks. Patients returned for follow-up visits after 7 months. Clinical outcomes were determined by the improvement of neuropsychological test scores at the end of the treatment. Grouped by CDR scores, changes in neuropsychological tests scores among different GPI groups were used to explore the correlation between severity of dementia and clinical outcomes. Univariate analysis and multivariate linear regression analysis were used to identify factors that may predict the clinical outcomes. Results (1)After penicillin therapy, GPI patients' MMSE scores(14.4± 6.9 vs.17.1 ± 9.1)and IADL scores(4.0(2.0, 5.0)vs.6.0(2.0, 7.3))both improved significantly(t=5.820, Z=3.710, P<0.01),while in ADAS-Cog, only factor scores of attention(1.5(0.7, 3.0)vs.1.5(0, 2.3))reduced significantly(Z=- 2.680, P<0.01). NPI's total scores(46.0 ± 27.1 vs.17.6 ± 15.4)and subscores of hallucination, delusion, agitation, depression, euphoria, disinhibition and irritability reduced significantly (Z=-4.940,-2.381,-2.504,-3.095,-2.492,-3.097,-2.527,-3.715, all P<0.05).(2) Grouped by the CDR scores, MMSE scores and IADL scores in very mild GPI group with CDR=0.5 improved significantly. In mild GPI group with CDR=1, significant changes were also found in all neuropsychological tests scores(MMSE,t=5.409, P<0.01), total scores of ADAS-Cog (Z=-2.366,P<0.05), IADL (Z=2.546, P<0.05), total scores of NPI (Z=-3.558,P<0.01), but except for PSMS. In moderate to severe GPI group with CDR>1,significant change was found only in total scores of NPI (t=-3.772,P<0.05). (3) Univariate analysis and multivariate linear regression analysis showed that improvement of MMSE scores after the treatment was significantly correlated with IADL scores and MMSE scores at baseline(β=0.541,P=0.004;β=0.364,P=0.044). Conclusions After penicillin treatment, GPI patients may improve in both cognitive function and psychotic symptoms but not in all the domains. Symptoms of anxiety, sleep/nigh-time behavior change, and apathy, as well as moderate to severe GPI patients may not benefit much from the treatment.

Objective To investigate the characteristics of cognitive impairment and psychotic symptoms in general paresis of insane (GPI) before and after penicillin therapy, and explore factors that may predict the clinical outcomes. Methods Thirty patients with GPI were recruited. All GPI patients underwent a comprehensive neuropsychological assessment before receiving penicillin therapy, and returned for follow-up visits after 7 months. The severity of dementia was determined by Clinical Dementia Rating Scale (CDR), cognitive functions were assessed by Mini Mental State Examination (MMSE) and Alzheimer 's Disease Assessment Scale-cognitive subscale (ADAS-Cog), ability of daily living was assessed by Instrumental Activities of Daily Living Scale (IALD) and Physical Self maintenance Scale(PSMS), behavioral and psychological symptoms were assessed by Neuropsychiatric Inventory (NPI). Aqueous crystalline penicillin G 24 million units per day was administered as continuous infusion for 14 days, followed by benzathine penicillin 2.4 million units IM once per week for 3 weeks. Patients returned for follow-up visits after 7 months. Clinical outcomes were determined by the improvement of neuropsychological test scores at the end of the treatment. Grouped by CDR scores, changes in neuropsychological tests scores among different GPI groups were used to explore the correlation between severity of dementia and clinical outcomes. Univariate analysis and multivariate linear regression analysis were used to identify factors that may predict the clinical outcomes. Results (1)After penicillin therapy, GPI patients' MMSE scores(14.4± 6.9 vs.17.1 ± 9.1)and IADL scores(4.0(2.0, 5.0)vs.6.0(2.0, 7.3))both improved significantly(t=5.820, Z=3.710, P<0.01),while in ADAS-Cog, only factor scores of attention(1.5(0.7, 3.0)vs.1.5(0, 2.3))reduced significantly(Z=- 2.680, P<0.01). NPI's total scores(46.0 ± 27.1 vs.17.6 ± 15.4)and subscores of hallucination, delusion, agitation, depression, euphoria, disinhibition and irritability reduced significantly (Z=-4.940,-2.381,-2.504,-3.095,-2.492,-3.097,-2.527,-3.715, all P<0.05).(2) Grouped by the CDR scores, MMSE scores and IADL scores in very mild GPI group with CDR=0.5 improved significantly. In mild GPI group with CDR=1, significant changes were also found in all neuropsychological tests scores(MMSE,t=5.409, P<0.01), total scores of ADAS-Cog (Z=-2.366,P<0.05), IADL (Z=2.546, P<0.05), total scores of NPI (Z=-3.558,P<0.01), but except for PSMS. In moderate to severe GPI group with CDR>1,significant change was found only in total scores of NPI (t=-3.772,P<0.05). (3) Univariate analysis and multivariate linear regression analysis showed that improvement of MMSE scores after the treatment was significantly correlated with IADL scores and MMSE scores at baseline(β=0.541,P=0.004;β=0.364,P=0.044). Conclusions After penicillin treatment, GPI patients may improve in both cognitive function and psychotic symptoms but not in all the domains. Symptoms of anxiety, sleep/nigh-time behavior change, and apathy, as well as moderate to severe GPI patients may not benefit much from the treatment.