Mental disorders frequently co-occur with other physical illnesses,becoming one of the leading causes of disability worldwide.Early diagnosis and intervention are crucial for the effective management of these disorders.Currently,biomarker studies on mental disorders predominantly concentrate on genes,blood indicators,and imaging features of the brain.There is a growing interest in objective phenotypic markers as a research focus.It is established that the retina is part of the central nervous system(CNS),which extends from the mesencephalon and develops concurrently with the brain during the embryonic period.Given the overlapping pathophysiological mechanisms between neurodegenerative diseases and mental disorders,studying the structural and functional changes in the inner layers of the retina has emerged as a new direction in mental health research.The advent of optical coherence tomography(OCT)has enabled microscopic imaging of retinal structures.OCT is capable of objectively quantifying the retinal sub-layers and offers the advantages of being non-invasive,non-contact,and high-resolution.The use of OCT to explore structural changes in the retina among individuals with schizophrenia,bipolar disorder,major depression and other psychiatric disorders has been well documented;however,there is a paucity of reviews on this topic.This review summarizes current research on retinal structural alterations in patients with mental disorders,and the results demonstrate reduced thickness in certain sub-layers of the retina structure in patients with several mental disorders,which supports that the retina structure has the potential to be a biomarker for mental disorders and offers a novel avenue for research in the diagnosis and treatment.

Objective To investigate the drug-drug interaction between donepezil hydrochloride and moxifloxacin hydrochloride during combined administration through in vitro liver microsomal metabolism and changes in pharmacokinetic characteristics in rats.Methods A rat liver microsomal incubation system was constructed and optimized.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis of donepezil hydrochloride and high-performance liquid chromatography(HPLC)analysis of moxifloxacin hydro-chloride were performed.The pharmacokinetic and metabolic characteristics of the two drugs,alone and in combination,were compared in vitro using rat liver microsomes and in vivo using rats.Results In the liver microsomal system,the half-life(T1/2)of donepezil hydro-chloride in the combined administration 1 group was prolonged by 29.892％(P＜0.01)and the intrinsic clearance(CLint)was reduced by 23.194％(P＜0.01)compared with the donepezil hydrochloride group.Conversely,the metabolic parameters of moxifloxacin hydrochlo-ride in the combined administration 2 group did not differ significantly from that of the moxifloxacin hydrochloride group(P＞0.05).In the in vivo study,the AUC0～t and AUC0～∞ of donepezil hydrochloride in the combined administration 1 group increased by 44.259％and 44.496％,respectively,maximum plasma concentration(Cmax)increased by 117.723％,T1/2 was prolonged by 98.063％,and CLint was reduced by 35.293％,compared with that in the donepezil hydrochloride group.Moreover,the differences were all statistically significant(P＜0.05).The in vivo study findings were consistent with the results of the in vitro study.Conclusion A drug-drug interaction occurs when moxifloxacin hydrochloride is used in combination with donepezil hydrochloride.Moxifloxacin hydrochloride promotes the absorption of donepezil hydrochloride,inhibits its metabolism,slows its CLint,and increases donepezil exposure in the body.

OBJECTIVE: To investigate the application value of pediatric sepsis-induced coagulation (pSIC) score and mean platelet volume/platelet count (MPV/PLT) ratio in the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis. METHODS: A retrospective cohort study was conducted, selecting 112 children with sepsis (sepsis group) admitted to pediatric intensive care unit (PICU) of Liaocheng Second People's Hospital from January 2020 to December 2023 as the study objects, and 50 children without sepsis admitted to the pediatric surgery department of our hospital during the same period for elective surgery due to inguinal hernia as the control (control group). The children with sepsis were divided into two groups according to the pediatric critical case score (PCIS). The children with PCIS score of ≤ 80 were classified as critically ill group, and those with PCIS score of > 80 was classified as non-critically ill group. pSIC score, coagulation indicators [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen (FIB)], and platelet related indicators (PLT, MPV, and MPV/PLT ratio) were collected. Pearson correlation method was used to analyze the correlation between pSIC score and MPV/PLT ratio as well as their correlation with coagulation indicators. Multivariate Logistic regression analysis was used to screen the independent risk factors for pediatric sepsis and critical pediatric sepsis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the application value of the above independent risk factors on the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis. RESULTS: 112 children with sepsis and 50 children without sepsis were enrolled in the final analysis. pSIC score, PT, INR, APTT, FIB, MPV, and MPV/PLT ratio in the sepsis group were significantly higher than those in the control group [pSIC score: 0.93±0.10 vs. 0.06±0.03, PT (s): 14.76±0.38 vs. 12.23±0.15, INR: 1.26±0.03 vs. 1.06±0.01, APTT (s): 40.08±0.94 vs. 32.47±0.54, FIB (g/L): 3.51±0.11 vs. 2.31±0.06, MPV (fL): 8.86±0.14 vs. 7.62±0.11, MPV/PLT ratio: 0.037±0.003 vs. 0.022±0.001, all P < 0.01], and PLT was slightly lower than that in the control group (×10⁹/L: 306.00±11.01 vs. 345.90±10.57, P > 0.05). Among 112 children with sepsis, 46 were critically ill and 66 were non-critically ill. pSIC score, PT, INR, APTT, MPV, and MPV/PLT ratio in the critically ill group were significantly higher than those in the non-critically ill group [pSIC score: 1.74±0.17 vs. 0.36±0.07, PT (s): 16.55±0.80 vs. 13.52±0.23, INR: 1.39±0.07 vs. 1.17±0.02, APTT (s): 43.83±1.72 vs. 37.77±0.95, MPV (fL): 9.31±0.23 vs. 8.55±0.16, MPV/PLT ratio: 0.051±0.006 vs. 0.027±0.001, all P < 0.05], PLT was significantly lower than that in the non-critically ill group (×10⁹/L: 260.50±18.89 vs. 337.70±11.90, P < 0.01), and FIB was slightly lower than that in the non-critically ill group (g/L: 3.28±0.19 vs. 3.67±0.14, P > 0.05). Correlation analysis showed that pSIC score was significantly positively correlated with MPV/PLT ratio and coagulation indicators including PT, APTT and INR in pediatric sepsis (r value was 0.583, 0.571, 0.296 and 0.518, respectively, all P < 0.01), and MPV/PLT ratio was also significantly positively correlated with PT, APTT and INR (r value was 0.300, 0.203 and 0.307, respectively, all P < 0.05). Multivariate Logistic regression analysis showed that pSIC score and MPV/PLT ratio were independent risk factors for pediatric sepsis and critical pediatric sepsis [pediatric sepsis: odds ratio (OR) and 95% confidence interval (95%CI) for pSIC score was 14.117 (4.190-47.555), and the OR value and 95%CI for MPV/PLT ratio was 1.128 (1.059-1.202), both P < 0.01; critical pediatric sepsis: the OR value and 95%CI for pSIC score was 8.142 (3.672-18.050), and the OR value and 95%CI for MPV/PLT ratio was 1.068 (1.028-1.109), all P < 0.01]. ROC curve analysis showed that pSIC score and MPV/PLT ratio had certain application value in the diagnosis of pediatric sepsis [area under the ROC curve (AUC) and 95%CI was 0.754 (0.700-0.808) and 0.720 (0.643-0.798), respectively] and the determination of critical pediatric sepsis [AUC and 95%CI was 0.849 (0.778-0.919) and 0.731 (0.632-0.830)], and the combined AUC of the two indictors was 0.815 (95%CI was 0.751-0.879) and 0.872 (95%CI was 0.806-0.938), respectively. CONCLUSIONS pSIC score and MPV/PLT ratio have potential application value in the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis, and the combined application of both is more valuable.
Humans ; Sepsis/complications* ; Platelet Count ; Mean Platelet Volume ; Retrospective Studies ; Child ; Blood Coagulation Disorders/diagnosis* ; Intensive Care Units, Pediatric ; Male ; Female ; Partial Thromboplastin Time ; Child, Preschool ; Blood Coagulation ; International Normalized Ratio ; Infant

Objective To explore the role of the brief visuospatial memory test-revised(BVMT-R)in predicting the clinical conversion to psychosis in subjects with clinical high-risk for psychosis(CHR-P).Methods A total of 217 CHR subjects were recruited and assessed using BVMT-R at baseline.Participants were followed up for three years to determine whether they converted to psychosis.The relationship between BVMT-R total score and CHR-P conversion probability was analyzed using generalized additive model,and the cutoff values of BVMT-R total score for predicting CHR-P conversion were calculated by maximally selected rank statistics.Then,the total BVMT-R score was stratified into different intervals based on the cutoff values obtained as previously described.Finally,the positive likelihood ratios and the conversion rates at different time points were calculated for each interval.Results A total of 168 subjects with CHR-P completed the 3-year follow-up assessment.According to the results of the generalized additive model,the relationship between the BVMT-R total score and CHR-P conversion probability exhibited the characteristics of a piecewise function model.The cutoff values identified using the maximally selected rank statistics method were 18 and 29,which divided the BVMT-R total scores into three intervals:0-18,19-29,and 30-36.The positive likelihood ratios of the three intervals for predicting CHR-P psychosis conversion were significantly different(all P<0.01).All three intervals had significantly different rates of psychosis conversion at different follow-up time points(all P<0.01).Conclusion The total BVMT-R score can be divided into three intervals,each associated with a distinct positive likelihood ratio for predicting psychosis conversion in CHR-P individuals.Accordingly,the BVMT-R total score may serve as a preliminary indicator for estimating the probability of psychosis conversion in the CHR-P population.

Objective:To analyze the inflammatory indexes and cytokines levels in serum and saliva of patients with chronic periodontitis(CP),and to explore the value of single index or multiple indexes combined detection in the clinical diagnosis and treatment of CP.Methods:The serum and saliva speci-mens of 42 CP patients and 38 periodontal healthy people admitted to the Department of Periodontology in Peking University Hospital of Stomatology were detected by inflammatory indexes and cytokines.Accord-ing to clinical periodontal parameters,CP patients were performed by clinical staging,and the correlation between inflammatory indexes and cytokines levels and the severity of CP was analyzed.To evaluate the levels of inflammatory indexes and cytokines in serum and saliva samples in the periodontal health group and CP group.Three inflammatory indexes were involved in this study:C-reactive protein(CRP),serum amyloid A(SAA),procalcitonin(PCT);and 12 cytokines:Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12P70,IL-17,interferon(IFN)-α,IFN-γ,and tumor necrosis factor α(TNF-α).The Spearman correlation statistical method was used to analyze the correlation between the levels of inflammatory indexes and cytokines and the severity of chronic periodontitis.Mann-Whitney U test was used to identify the indicators with differences between the groups,the optimal indicators were identified through binary Logistic regression analysis with stepwise selection,and the area under the curve(AUC)of receiver operating characteristic(ROC)was used to evaluate the diagnostic efficiency.Results:By testing the levels of inflammatory markers and cytokines in patients with chronic periodontitis with dif-ferent clinical stages,it was found that CRP,SAA,IL-8 in serum and IL-1β,IL-6,IL-8,IL-12P70,IL-17,TNF-α in saliva were significantly positively correlated with the severity of chronic periodontitis.Compared with the periodontal healthy group,the serum levels of CRP,SAA,IL-2,IL-5,IL-8,IL-12P70,IL-17 and IFN-α in the CP group were significantly increased(All P＜0.05).The AUC of SAA,IL-2,IL-8,IL-12P70,IL-17,IFN-α,combination 1(IL-2+IL-8)and combination 2(CRP+SAA+IL-12P70)were＞0.7,and the AUC of combination 2(0.998)was the highest,with high sensi-tivity(97.6％)and specificity(97.4％).The levels of IL-1β,IL-6,IL-8 and IL-12P70 in the saliva of the CP group were significantly higher than those in the periodontal healthy group,while the levels of IL-4 in the saliva were significantly lower than those in the periodontal healthy group(All P＜0.05).The AUC of IL-6,IL-8 and combination 3(IL-4+IL-6+IL-8)were＞0.7,and the AUC of combina-tion 3(0.852)was the highest.In the comparative analysis of diagnostic efficacy between single index and multi-index combined,combination 2,combination 1,and serum IL-8 demonstrated the highest AUC values(ranked top 3),with multi-index combinations exhibiting superior discriminative power over single index.Conclusion:Serum levels of IL-8,CRP,SAA,and salivary levels of IL-1β,IL-6,IL-8,and other indicators may be helpful for the clinical diagnosis and treatment of CP.Serum IL-8 and multiple indicators may be used as an auxiliary diagnostic indice to identify CP.

Objective:To investigate the risk factors of pediatric sepsis-induced coagulopathy（pSIC），and to construct a nomogram prediction model for early prediction of pSIC.Methods:Using a cross-sectional retrospective cohort design，children with sepsis who were hospitalized in PICU of the Second People's Hospital of Liaocheng Subsidiary to Shandong First Medical University from January 2017 to December 2023 were selected as the study objects，and the diagnosis of sepsis met the diagnostic criteria for childhood sepsis of the 2015 edition.According to the diagnostic criteria of pSIC，the children with sepsis were divided into common sepsis group and pSIC group.The clinical data of both groups were compared，such as general condition，inflammatory indicators，coagulation indicators，sequential organ failure assessment（pSOFA），pSIC score，PICU duration，etc.The risk factors of pSIC were initially screened by Lasso regression analysis，and the independent risk factors were screened by multivariate Logistic regression analysis.R software was used to construct the risk prediction nomogram and evaluate the model.Results:A total of 150 children with sepsis were included in the study，including 121 in the common sepsis group and 29 in the pSIC group.Lasso regression and multivariate Logistic regression analysis showed that pSOFA，prothrombin time（PT），alanine aminotransferase（ALT），blood urea nitrogen（BUN），mean platelet volume/platelet（MPV/PLT）and pediatric critical illness score(PCIS) were independent risk factors for pSIC（all P<0.05）.Since the sources of the pSIC score overlaped with those of pSOFA and PT, only four indicators including ALT，BUN，MPV/PLT and PCIS were used to construct a nomogram model for predicting pSIC.The consistency index of the nomogram model was 0.98，and the area under the receiver operating characteristic curve was 0.975（95% CI 0.952-0.999）.The calibration curve was shown as a straight line with slope close to 1，indicating that the nomogram model had good accuracy in predicting pSIC.The clinical decision curve indicated that the nomogram model had good clinical applicability. Conclusion:pSOFA，PT，ALT，BUN，MPV/PLT and PCIS were all independent risk factors for pSIC.The risk prediction nomogram model of pSIC based on ALT，BUN，MPV/PLT and PCIS can predict the occurrence of pSIC，and provide reference for early clinical recognition and intervention.

Objective To explore the role of the brief visuospatial memory test-revised(BVMT-R)in predicting the clinical conversion to psychosis in subjects with clinical high-risk for psychosis(CHR-P).Methods A total of 217 CHR subjects were recruited and assessed using BVMT-R at baseline.Participants were followed up for three years to determine whether they converted to psychosis.The relationship between BVMT-R total score and CHR-P conversion probability was analyzed using generalized additive model,and the cutoff values of BVMT-R total score for predicting CHR-P conversion were calculated by maximally selected rank statistics.Then,the total BVMT-R score was stratified into different intervals based on the cutoff values obtained as previously described.Finally,the positive likelihood ratios and the conversion rates at different time points were calculated for each interval.Results A total of 168 subjects with CHR-P completed the 3-year follow-up assessment.According to the results of the generalized additive model,the relationship between the BVMT-R total score and CHR-P conversion probability exhibited the characteristics of a piecewise function model.The cutoff values identified using the maximally selected rank statistics method were 18 and 29,which divided the BVMT-R total scores into three intervals:0-18,19-29,and 30-36.The positive likelihood ratios of the three intervals for predicting CHR-P psychosis conversion were significantly different(all P<0.01).All three intervals had significantly different rates of psychosis conversion at different follow-up time points(all P<0.01).Conclusion The total BVMT-R score can be divided into three intervals,each associated with a distinct positive likelihood ratio for predicting psychosis conversion in CHR-P individuals.Accordingly,the BVMT-R total score may serve as a preliminary indicator for estimating the probability of psychosis conversion in the CHR-P population.

Objective·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation(TMS)treatment in patients with major depressive disorder(MDD)and explore their correlation with the antidepressant and anxiolytic efficacy of TMS.Methods·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,were included in this study between January 2018 and August 2023.Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale(HAMD),Montgomery-Asberg Depression Rating Scale(MADRS),and Hamilton Anxiety Scale(HAMA)at baseline and post-TMS treatment.Patients underwent a baseline magnetic resonance imaging(MRI)scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex(DLPFC)at a frequency of 10 Hz,totaling 20 sessions.A follow-up MRI scan was conducted on the same day the TMS treatment concluded.Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software.Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance.Controlling for age,sex,and intracranial volume,partial correlation analysis was conducted between subfield volumes and baseline clinical scores.The association between the rate of volume change in brain regions with significant volume changes and symptom improvement(reduction in HAMD,MADRS,and HAMA scores)was evaluated.Results·Following TMS treatment,a significant increase in the volume of the right amygdala central nucleus was observed(t=-2.441,P=0.018).While the volumes of bilateral hippocampal fimbria decreased,the volumes of most hippocampal subfield and the total hippocampus increased(P<0.05).No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms.However,only in patients who responded effectively to TMS treatment,a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms(HAMA:r=0.334,P=0.044).Conclusion·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields.Additionally,the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders,suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.

Objective:To analyze the inflammatory indexes and cytokines levels in serum and saliva of patients with chronic periodontitis(CP),and to explore the value of single index or multiple indexes combined detection in the clinical diagnosis and treatment of CP.Methods:The serum and saliva speci-mens of 42 CP patients and 38 periodontal healthy people admitted to the Department of Periodontology in Peking University Hospital of Stomatology were detected by inflammatory indexes and cytokines.Accord-ing to clinical periodontal parameters,CP patients were performed by clinical staging,and the correlation between inflammatory indexes and cytokines levels and the severity of CP was analyzed.To evaluate the levels of inflammatory indexes and cytokines in serum and saliva samples in the periodontal health group and CP group.Three inflammatory indexes were involved in this study:C-reactive protein(CRP),serum amyloid A(SAA),procalcitonin(PCT);and 12 cytokines:Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12P70,IL-17,interferon(IFN)-α,IFN-γ,and tumor necrosis factor α(TNF-α).The Spearman correlation statistical method was used to analyze the correlation between the levels of inflammatory indexes and cytokines and the severity of chronic periodontitis.Mann-Whitney U test was used to identify the indicators with differences between the groups,the optimal indicators were identified through binary Logistic regression analysis with stepwise selection,and the area under the curve(AUC)of receiver operating characteristic(ROC)was used to evaluate the diagnostic efficiency.Results:By testing the levels of inflammatory markers and cytokines in patients with chronic periodontitis with dif-ferent clinical stages,it was found that CRP,SAA,IL-8 in serum and IL-1β,IL-6,IL-8,IL-12P70,IL-17,TNF-α in saliva were significantly positively correlated with the severity of chronic periodontitis.Compared with the periodontal healthy group,the serum levels of CRP,SAA,IL-2,IL-5,IL-8,IL-12P70,IL-17 and IFN-α in the CP group were significantly increased(All P＜0.05).The AUC of SAA,IL-2,IL-8,IL-12P70,IL-17,IFN-α,combination 1(IL-2+IL-8)and combination 2(CRP+SAA+IL-12P70)were＞0.7,and the AUC of combination 2(0.998)was the highest,with high sensi-tivity(97.6％)and specificity(97.4％).The levels of IL-1β,IL-6,IL-8 and IL-12P70 in the saliva of the CP group were significantly higher than those in the periodontal healthy group,while the levels of IL-4 in the saliva were significantly lower than those in the periodontal healthy group(All P＜0.05).The AUC of IL-6,IL-8 and combination 3(IL-4+IL-6+IL-8)were＞0.7,and the AUC of combina-tion 3(0.852)was the highest.In the comparative analysis of diagnostic efficacy between single index and multi-index combined,combination 2,combination 1,and serum IL-8 demonstrated the highest AUC values(ranked top 3),with multi-index combinations exhibiting superior discriminative power over single index.Conclusion:Serum levels of IL-8,CRP,SAA,and salivary levels of IL-1β,IL-6,IL-8,and other indicators may be helpful for the clinical diagnosis and treatment of CP.Serum IL-8 and multiple indicators may be used as an auxiliary diagnostic indice to identify CP.

Objective·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation(TMS)treatment in patients with major depressive disorder(MDD)and explore their correlation with the antidepressant and anxiolytic efficacy of TMS.Methods·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,were included in this study between January 2018 and August 2023.Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale(HAMD),Montgomery-Asberg Depression Rating Scale(MADRS),and Hamilton Anxiety Scale(HAMA)at baseline and post-TMS treatment.Patients underwent a baseline magnetic resonance imaging(MRI)scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex(DLPFC)at a frequency of 10 Hz,totaling 20 sessions.A follow-up MRI scan was conducted on the same day the TMS treatment concluded.Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software.Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance.Controlling for age,sex,and intracranial volume,partial correlation analysis was conducted between subfield volumes and baseline clinical scores.The association between the rate of volume change in brain regions with significant volume changes and symptom improvement(reduction in HAMD,MADRS,and HAMA scores)was evaluated.Results·Following TMS treatment,a significant increase in the volume of the right amygdala central nucleus was observed(t=-2.441,P=0.018).While the volumes of bilateral hippocampal fimbria decreased,the volumes of most hippocampal subfield and the total hippocampus increased(P<0.05).No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms.However,only in patients who responded effectively to TMS treatment,a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms(HAMA:r=0.334,P=0.044).Conclusion·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields.Additionally,the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders,suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.