The onset of pregnancy is marked by the formation of a zygote, while the culmination of gestation is manifested by the delivery of a fetus. Meanwhile, a successful pregnancy entails a meticulously coordinated sequence of events from embryo implantation to sustained decidualization of the uterus to placental development and childbirth. The decidual reaction, a pivotal process occurring within the endometrium during pregnancy, is finely regulated by sex steroids and cytokines. Notably, fibroblast growth factors (FGFs), particularly FGF2, play a critical role in this physiological cascade. Dysregulated FGF expression may trigger inadequate decidualization, precipitating a spectrum of adverse pregnancy outcomes, including preeclampsia, recurrent implantation failure, and miscarriage. Furthermore, the human decidua, distinct from most mammalian species and similar to great apes, undergoes regular cycles of formation and shedding, independent of the presence of the embryo in the endometrium. This process is also tightly controlled by various FGFs. In this review, we comprehensively compare diverse research decidualization models, delineate the trend of endometrial FGFs during the menstrual cycle, and provide a synopsis of endometrial diseases triggered by FGF dysregulation.
Humans ; Female ; Pregnancy ; Decidua/physiology* ; Animals ; Endometrium/physiology* ; Fibroblast Growth Factors/metabolism* ; Embryo Implantation ; Menstrual Cycle/physiology*

Objective:This study aims to analyze the gamma band effective connectivity characteristics of the prefrontal-striatal circuitry in bipolar disorder patients with and without a history of manic episodes, as well as in major depressive disorder patients, during the recognition of positive emotional faces, this study aims to identify unique neurophysiological features that may aid in the early detection of bipolar disorder.Methods:This retrospective study collected clinical data and magnetoencephalography (MEG) imaging data from patients performing a positive emotional face recognition task at the Affiliated Brain Hospital of Nanjing Medical University from May 2009 to December 2019. The study included 75 patients with major depressive disorder and 29 patients with bipolar disorder in a depressive episode (rBD group). Concurrently, 39 age-and gender-matched healthy controls (HC group) were recruited. After a follow-up period of at least 5 years, 23 out of the 75 patients with major depressive disorder converted to bipolar disorder (ctBD group), while the remaining 52 who did not convert maintained a diagnosis of major depressive disorder.Results:There were statistically significant differences in gamma-band effective connectivity in the prefrontal-striatal circuit when recognizing positive emotional faces among the converted to bipolar disorder (ctBD), raw bipolar disorder, major depressive disorder, and HC groups ( H=9.04, 10.30, 8.30, 13.43, 14.38, 12.62, 9.82, 8.94, 24.62, 7.89, 18.53, 9.97, 9.58, 12.79, P<0.05). The ctBD group, rBD group, and major depressive group all showed reduction in effective connectivity from the right orbital inferior frontal gyrus (ORBinf.R) to the left orbital inferior frontal gyrus (ORBinf.L) [ Z=-1.98, -3.38, -2.88], from the right orbital inferior frontal gyrus to the right ventral striatum (VS.R) ( Z=-2.05, -2.76, -2.11; P<0.05) and from the left ventral striatum (VS.L) to the left orbital middle frontal gyrus (ORBmid.L) ( Z=-2.76, -1.98, -2.43; P<0.05). Among the disease groups, the ctBD group showed significantly enhanced effective connectivity strength compared to the major depressive group from the right amygdala (AMYG.R) to the left orbital inferior frontal gyrus(0.04(0.03, 0.08)), from the right amygdala to the left ventral striatum(0.05(0.03, 0.09)), and from the right ventral striatum to the right anterior cingulate and paracingulate gyri (ACG.R) (0.04(0.02, 0.08)) ( Z=4.17, 3.70, 3.35; P<0.001).The ctBD group also exhibited enhanced effective connectivity compared to the rBD group from ORBinf.R to the ACG.R, fron the AMYG.R to the ORBinf.L, from the AMYG.R to the VS.L, and from the VS.R to the ACG.R ( Z=2.05, 4.61, 3.60, 3.04; P<0.05).The rBD group demonstrated reduced effective connectivity compared to the major depressive disorder group from the right orbital middle frontal gyrus(ORBmid.R) to the left anterior cingulate and paracingulate gyri (ACG.L), ORBinf.R to the ACG.R and from the ORBinf.R to the AMYG.R ( Z=-2.12, -2.40, -2.22; P<0.05). Conclusion:There are significant differences in the gamma-band effective connectivity characteristics of the prefrontal-striatal pathway when recognizing positive emotional faces between patients with bipolar disorder in depressive episodes and those with depression, as well as differences between bipolar depressed patients with and without a history of manic episodes.

Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.

Objective:To explore the differences in the whole-brain functional connectivity characteristics of magnetoencephalography gamma sub-band in resting state between patients with depression with high and low suicidal ideation.Methods:Clinical data of 60 patients with depression (depression group) who visited the Department of Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University from October 2021 to June 2024 were prospectively collected, including 20 males and 40 females aged 16-41 years. During the same period, 75 healthy controls (healthy control group) were recruited, matched for gender and age, comprising 33 males and 42 females, aged 18-43 years. The Hamilton Depression Scale-17 items (HAMD-17) was used to assess the degree of depression in patients, and the score of the third item was used to divide the patients into a high suicidal ideation group of 37 cases (2-3 points) and a low suicidal ideation group of 23 cases (0-1 points). The Beck Scale for Suicide Ideation-Chinese Version (BSI-CV) was used to assess the intensity of suicidal ideation in patients in the last week and at the most severe stage. Brain imaging data of the subjects were collected using a CTF-275 channel magnetoencephalography device and a 3 T magnetic resonance imaging device. The functional connectivity matrix of the gamma sub-band depression group, healthy control group, high suicidal ideation group, and low suicidal ideation group was calculated using the envelope correlation method. The network-based statistics (NBS) algorithm was used to correct for multiple comparisons and compare the differences in brain network functional connectivity between the depression group/healthy control group and between the high/low suicidal ideation groups.Results:Compared with the healthy control group, the functional connectivity between the bilateral middle frontal gyrus, right inferior frontal gyrus orbital part, right anterior cingulate gyrus, left middle frontal gyrus orbital part, and right superior parietal lobule in the depression group was significantly enhanced in the low gamma frequency band (30-60 Hz) ( θ=3, P=0.042). Compared with the low suicidal ideation group, the functional connectivity between the right amygdala as a central node and the right superior frontal gyrus, left hippocampus, right upper temporal pole, and left transverse temporal gyrus in the high suicidal ideation group was significantly enhanced in the high gamma frequency band (60-90 Hz) ( θ=3, P=0.049). Conclusion:In the low gamma frequency band, patients with depression have neural dysfunction mainly in the frontal lobe. In the high gamma frequency band, patients with high suicidal ideation have functional connectivity abnormalities centered on the amygdala.

Objective:To explore behavioral and electrophysiological differences in risky decision-making between depressed patients with and without suicidal ideation.Methods:A total of 61 patients with first-episode untreated depression were enrolled in the depression clinic of Nanjing Brain Hospital from September 2023 to January 2024, which were divided into the suicidal ideation group( n=32) and the non-suicidal ideation group ( n=29).At the same time, healthy controls matched with sex, age and years of education were recruited from the community( n=36).The event-related potentials (ERP) of the participants were detected, and the amplitude and latency of feedback related negative waves (FRN) and P300 during the feedback phase under Iowa gambling task (IGT) were recorded. Statistical analysis was performed using SPSS 26.0 software.The inter-and intra-group differences of ERP indexes were compared using two-way ANOVA, and Spearman correlation analysis was conducted to examine the relationship between ERP indexes and scores of the Beck scale for suicidal ideation. Results:(1)Compared with healthy controls, depressed patients with and without suicidal ideation had both lower net scores in IGT (both P<0.05).(2)When comparing the mean FRN amplitude under different feedback types among the three groups, the main effect of feedback type ( F=8.799, P=0.004), the main effect of group ( F=6.396, P=0.002) and the interaction effect ( F=4.200, P=0.018)were all significant. Under gain feedback conditions, the mean FRN amplitude was lower in both depressed groups compared with healthy controls (both P<0.05). (3)The comparison of the mean P300 amplitude under different feedback types among the three groups showed that the main effect of group ( F=15.719, P<0.001) and the main effect of feedback type ( F=15.949, P=0.001) were both significant, while the interaction effect between group and feedback type was not significant ( F=1.573, P=0.213). The group with suicidal ideation ((0.85±0.21) μV) had a smaller amplitude than both the non-suicidal ideation group ((1.61±0.22) μV) and healthy controls ((2.46±0.20) μV) (both P<0.05). (4)In depressed patients, P300 mean amplitude under both loss and gain feedback conditions were both negatively correlated with suicidal ideation (loss: r=-0.435, P=0.001; gain: r=-0.318, P=0.013). Conclusion:Depressed patients with and without suicidal ideation both exhibit impaired risk decision-making. The decrease of P300 mean amplitude is more significant in depressed patients with suicidal ideation than those without suicidal ideation.P300 mean amplitude may serve as an electrophysiological marker to differentiate depressed patients with suicidal ideation and those without suicidal ideation.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective:To analyze the characteristics of electroencephalogram microstate parameters in first-episode drug-naive patients with major depressive disorder (MDD), so as to provide electrophysiological evidence for the pathogenesis and early diagnosis of MDD.Methods:Eighty-four first-episode, drug-naive outpatients diagnosed with MDD(MDD group) and 82 healthy controls(healthy group) participated in this study. Resting-state EEG data (5-6 min, with eyes closed) were recorded for all participants. Data preprocessing and microstate analysis were performed using MATLAB and EEGLAB software. Temporal parameters of resting-state brain network microstates were compared using SPSS 26.0.Results:This study identified four typical microstates: Class A microstate(auditory network), Class B microstate(visual network), Class C microstate(salient network), and Class D microstate(attention and control network). The coverage rate (0.16±0.06, 0.21±0.06), duration (67.72±7.07, 72.28±8.59), and incidence rate (2.38±0.68, 2.82±0.67) of microstate A in MDD group were significantly lower than those in healthy group ( F=22.115, 13.368, 18.779, all P<0.001), while the above indexes of microstate B in MDD group were significantly higher than those in healthy group(coverage rate: 0.24±0.07 vs 0.18±0.06, duration: 76.35±11.28 vs 69.46±8.52, incidence rat: 3.16±0.52 vs 2.52±0.57) ( F=41.287, 18.999, 52.245, all P<0.001). Additionally, the microstate D in MDD group showed significantly lower coverage rate(0.33±0.08, 0.36±0.08) and duration (89.66±15.38, 95.46±16.79)compared with healthy group( F=3.932, 4.215, both P<0.05). Notably, significant differences were observed in the transition probabilities between the following microstates: A→B, A→D, B→A, C→A, C→B, D→A and D→B (all P<0.05). Conclusion:First-episode drug-naive depressive patients are characterized by alterations in microstate A, microstate B, and microstate D, which may be the potential pathogenesis of MDD and may serve as electrophysiological indicators for early diagnosis of MDD.

Osteoporosis(OP)is a refractory metabolic bone disease,with decreased bone mineral mass,weakened bone strength,and systemic bone pain as typical clinical manifestations.Shenzhen Pingle Guo's Orthopedics,an important branch of the Pingle Guo's Orthopedics,has developed their distinct therapeutic approaches to the prevention and treatment of OP:the fifth-generation inheritor,Mr.Guo Chunyuan,advocated for the simultaneous regulation of qi and blood and formulated Shudi Zhuanggu Formula(composed of Rehmanniae Radix Praeparata,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Poria,Angelicae Sinensis Radix,Paeoniae Radix Alba,Chuanxiong Rhizoma,Dipsaci Radix,and Achyranthis Bidentatae Radix);the sixth-generation inheritor,Professor Yang Zejin,emphasized zang-fu syndrome differentiation and established Yang's Guwei Formula,which simultaneously tonifies the liver,spleen,and kidney,and simultaneously treats deficiency and blood stasis(composed of Astragali Radix,Rehmanniae Radix Praeparata,Achyranthis Bidentatae Radix,Epimedii Folium,Cistanches Herba,Cuscutae Semen,Drynariae Rhizoma,Angelicae Sinensis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Corydalis Rhizoma,and Paeoniae Radix Alba);the seventh-generation inheritor,Professor Gong Chunzhu,proposed a three-stage clinical treatment strategy and stressed the principle of reinforcing acquired foundation of life(i.e.,reinforcing spleen and stomach),and formulated the modified Shudi Zhuanggu Formula with Lingnan characteristics(composed of Rehmanniae Radix Praeparata,Corni Fructus,Dioscoreae Rhizoma,Alismatis Rhizoma,Poria,Moutan Cortex,Astragali Radix,Dipsaci Radix,Cyathulae Radix,Acanthopanacis Cortex,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,and Chaenomelis Fructus).During the evolution,Shenzhen Pingle Orthopedic Hospital has continuously integrated modern medical achievements,passed down and enriched the clinical experience,and then the theoretical framework of traditional Chinese medicine in the prevention and treatment of OP has been developed.

Objective:To explore behavioral and electrophysiological differences in risky decision-making between depressed patients with and without suicidal ideation.Methods:A total of 61 patients with first-episode untreated depression were enrolled in the depression clinic of Nanjing Brain Hospital from September 2023 to January 2024, which were divided into the suicidal ideation group( n=32) and the non-suicidal ideation group ( n=29).At the same time, healthy controls matched with sex, age and years of education were recruited from the community( n=36).The event-related potentials (ERP) of the participants were detected, and the amplitude and latency of feedback related negative waves (FRN) and P300 during the feedback phase under Iowa gambling task (IGT) were recorded. Statistical analysis was performed using SPSS 26.0 software.The inter-and intra-group differences of ERP indexes were compared using two-way ANOVA, and Spearman correlation analysis was conducted to examine the relationship between ERP indexes and scores of the Beck scale for suicidal ideation. Results:(1)Compared with healthy controls, depressed patients with and without suicidal ideation had both lower net scores in IGT (both P<0.05).(2)When comparing the mean FRN amplitude under different feedback types among the three groups, the main effect of feedback type ( F=8.799, P=0.004), the main effect of group ( F=6.396, P=0.002) and the interaction effect ( F=4.200, P=0.018)were all significant. Under gain feedback conditions, the mean FRN amplitude was lower in both depressed groups compared with healthy controls (both P<0.05). (3)The comparison of the mean P300 amplitude under different feedback types among the three groups showed that the main effect of group ( F=15.719, P<0.001) and the main effect of feedback type ( F=15.949, P=0.001) were both significant, while the interaction effect between group and feedback type was not significant ( F=1.573, P=0.213). The group with suicidal ideation ((0.85±0.21) μV) had a smaller amplitude than both the non-suicidal ideation group ((1.61±0.22) μV) and healthy controls ((2.46±0.20) μV) (both P<0.05). (4)In depressed patients, P300 mean amplitude under both loss and gain feedback conditions were both negatively correlated with suicidal ideation (loss: r=-0.435, P=0.001; gain: r=-0.318, P=0.013). Conclusion:Depressed patients with and without suicidal ideation both exhibit impaired risk decision-making. The decrease of P300 mean amplitude is more significant in depressed patients with suicidal ideation than those without suicidal ideation.P300 mean amplitude may serve as an electrophysiological marker to differentiate depressed patients with suicidal ideation and those without suicidal ideation.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.