Plasma-derived from human umbilical cord blood restores ovarian function and improves serum reproductive hormones levels in mice with premature ovarian insufficiency (POI) through cytokines and growth factors.

Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model. Initially, hUCB was utilized to obtain CBP (CBP), which was subsequently analyzed for cytokine and growth factor profiles in comparison to adult blood plasma (ABP) by use of flow cytometry. Subsequently, POI mouse models were established through the induction of 4-vinylcyclohexene diepoxide, followed by the injection of CBP into the tail. At 7, 14, and 21 days posttreatment, mouse ovaries and blood were collected, and their estrus cycle, body weight, and ovarian weights were evaluated using precise electronic balance. Finally, ovarian morphology and follicle number were assessed through HE staining, while serum levels of anti-Müllerian hormone (AMH), estradiol (E2) and follicle-stimulating hormone (FSH) were determined by ELISA. Our study revealed that individuals with CBP exhibited significantly lower concentrations of proinflammatory cytokines, including IL-ß (p < 0.01) and IL-2 (p < 0.05), while displaying elevated levels of anti-inflammatory cytokines and chemokines, such as IL-2, IL-4, IL-6, IL-8, IL-12P70, IL-17A, IP-10, interferon-γ, and tumor necrosis factor-α (p < 0.01). Furthermore, CBP demonstrated remarkably higher levels of growth factors, including transforming growth factor-ß1, vascular endothelial growth factor, and insulin-like growth factor-1 (p < 0.01) than ABP. Notably, our investigation also revealed that CBP restored the content of serum reproductive hormones, such as AMH, E2, and FSH (p < 0.05), and increased the number of primordial and primary follicles (p < 0.01) and decreased the number of luteal and atretic follicles (p < 0.01) in vivo. Our findings suggested that CBP-secreted cytokines and growth factors could be restored POI ovarian function, enhanced serum reproductive hormones and rescued follicular development in vivo. These findings further support the potential of CBP as a promising strategy in clinical applications for POI related infertility.

The effects of childhood trauma on personality in unaffected first-degree relatives of patients with major depressive disorder.

ABSTRAC: OBJECTIVES: This study aimed to preliminarily and exploratorily examine the associations between childhood trauma (CT), its subtypes, and personality traits among unaffected first-degree relatives (FDR, children, or siblings) of patients with major depressive disorder (MDD). METHODS: The study sample included three subgroups: MDD patients (N = 85), Patients' FDRs (N = 35), and healthy control individuals (HC, N = 89). The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma and the Eysenck Personality Questionnaire was used to assess personality traits. RESULTS: Significant differences were found in a few personality traits (p < 0.05 for extraversion, neuroticism, and psychoticism) among MDD patients, FDR, and HC, and there were no significant differences between HC and FDR. In the FDR group, compared with those without CT, participants with CT scored significantly higher for neuroticism (N) (F = 3.246, p = 0.046). CT was significantly associated with N, psychoticism (P) and Lie (L), and the strongest association was between CT total score and N. Significantly positive correlations were found between N and sexual abuse (SA) (r = 0.344, p = 0.043), emotional neglect (EN) (r = 0.394, p = 0.019), physical neglect (PN) (r = 0.393, p = 0.019), and CTQ total score (r = 0.452, p = 0.006); between P and CTQ total score (r = 0.336, p = 0.049); and significant negative correlations were found between L and EN (r = -0.446, p = 0.007), CTQ total score (r = -0.375, p = 0.027). CONCLUSION: In unaffected FDRs, there were significant associations between childhood trauma and a few personality traits, including neuroticism, psychoticism, and lie, and emotional neglect was significantly associated with neuroticism.

The Neglect of Left-Behind Children in China: A Meta-Analysis.

OBJECTIVE: To evaluate the neglect of left-behind children (LBC) in China. METHOD: Participants: Children separated from one or both parents for at least 6 months. Intervention: Trauma of separation. Comparison: Non-left-behind children (NLBC). Outcomes: Neglect rates and severity. Only case-control studies were included. RESULTS: Thirteen studies were included; there were 18,688 LBC in a large sample (N = 42,003) of children aged 0-18 years in China. The overall neglect rate was significantly higher in LBC compared to NLBC (odds ratio [OR] = 1.58, 95% confidence interval [CI] = [1.50, 1.67], p < .01) based on the Chinese Rural Child Neglected Evaluation Model (CRCNEM) and the Parents-Child Conflict Tactics Scales (OR = 1.44, 95% CI [1.35, 1.54], p < .01). The overall neglect severity in LBC was also significantly higher than NLBC (SMD = 0.31, 95% CI [0.28, 0.33], p < .01). The same trends were observed in sex subgroups. With regard to subtypes, LBC were significantly more likely to have emotional neglect (OR = 2.29, 95% CI [1.88, 2.78], p < .01), medical neglect (OR = 1.79, 95% CI [1.62, 1.98], p < .01), physical neglect (OR = 1.75, 95% CI [1.60, 1.91], p < .01), security neglect (OR = 1.52, 95% CI [1.32, 1.75], p < .01), educational neglect (OR = 1.50, 95% CI [1.31, 1.72], p < .01), and social neglect (OR = 1.33, 95% CI [1.18, 1.51], p < .01). Furthermore, LBC had significantly higher severity in medical neglect (SMD = 0.31, 95% CI [0.27, 0.35], p < .01), emotional neglect (SMD = 0.28, 95% CI [0.24, 0.32], p < .01), physical neglect (SMD = 0.24, 95% CI [0.18, 0.29], p < .01), security neglect (SMD = 0.26, 95% CI [0.23, 0.29], p < .01), educational neglect (SMD = 0.25, 95% CI [0.20, 0.31], p < .01), and social neglect (SMD = 0.25, 95% CI [0.10, 0.40], p < .01). CONCLUSION: The neglect rates and severity in LBC in China were both significantly higher than those in NLBC. There was a strong association between neglect and LBC. Public policy changes are urgently needed to improve the dire situation and the well-being of the LBC.

The effect of increased family finance and dual-parental absence since infancy on Children's cognitive Abilities.

Existing research suggests that parental absence per se does not have a main effect on children's cognitive development. However, this body of research is confounded by decreased family finance resulted from parental absence. Further insights on children's cognitive development can be gained by studying situations where parental absence actually leads to higher family finance. China's rural left-behind children (LBC) are uniquely suited for this purpose because of their extended separation from parents who migrated to work for better family finance. The participants were 74 LBC (M = 9.99 years, SD = 2.66) whose parents both migrated away for work within six months of their births and 74 non-left-behind children (NLBC) (M = 10.03 years, SD = 2.58) of similar backgrounds but whose parents never migrated. We used the 4th Edition of the Wechsler Intelligence Scale for Children (WISC-IV) to individually collected data on the children's Verbal Comprehension (which includes Similarities, Vocabulary, and Comprehension subtests), Perceptual Reasoning (which includes Block Design, Picture Concepts and Matric Reasoning subtests), Working Memory (which includes Digit Span and Letter-Number Sequencing subtests), and Processing Speed (which includes Coding and Symbol Search subtests). We found that the LBC scored lower than the NLBC on the language Comprehension and Vocabulary subtests of the Verbal Comprehension Index (Cohen's d = 0.41; p = .01). Subsequent General Linear Modeling analyses revealed that for the Comprehension subtest: (1) dual-parental absence significantly and negatively predicted Comprehension scores and (2) monthly family income significantly and positively predicted Comprehension scores for the LBC but not for the NLBC. For Vocabulary subtest, only dual-parental absence was significant. Overall, these results offer a deeper understanding on the effect of dual parental absence and changes in family finance on different domains of children's cognitive development.

Different aspects of cognitive function in adult patients with moyamoya disease and its clinical subtypes.

OBJECTIVE: Although a few reports suggested that cognitive function impairment could be found in adult patients with moyamoya disease (MMD), there were still many aspects that are unclear. The aim of our study was to assess the cognitive function of adult patients with MMD and its clinical subtypes. METHODS: 49 patients with MMD and 23 healthy controls were asked to take cognitive function tests. Cognitive function tests included IQ, prospective memory (PM), immediate memory (IM), verbal fluency (VF), visual breadth, attention, retrospective memory (RM), Stroop test, Wisconsin Card Sorting Test, Trail-Making Test Part A (TMT-A) and Continuous Performance Test (CPT). Independent t-analysis, one-way analysis of variance and Pearson correlation were used to seek for differences between subgroups and the correlation between cognitive variables. RESULTS: Compared with healthy controls, adult patients with MMD had a comprehensive cognitive impairment, including IQ, PM, VF, attention, RM, Stroop, CPT and TMT-A, with more serious impairment in PM and attention. PM and RM were separated, indicating that they were independent of each other. Pattern of attention was significantly different from healthy controls. Female patients were better than male patients, where significant differences in PM, IM, Stroop and WCST could be found. The haemorrhagic patients exhibited poorer in the dimension of PM and RM than the ischaemic. The headache subtype exhibited poorer than healthy controls. PM, RM, attention and executive function were moderately correlated with each other. CONCLUSIONS: Adult patients with MMD had a wide range of cognitive impairment with more serious impairment in memory and attention. Differences in cognitive function existed between the different subtypes of adult MMD.

The attenuated visual scanpaths of patients with schizophrenia whilst recognizing emotional facial expressions are worsened in natural social scenes.

Alteration of visual scanpaths under emotional facial expression in schizophrenia patients has been described in recent years; however, it is not clear whether such results are different when they transfer to faces in natural social scenes. The present study was designed to investigate the effects of emotional faces in natural social scenes on the gaze patterns of patients with schizophrenia, compared to gaze at isolated faces. A novel theme identification task was used where participants selected a positive, neutral or negative word to describe an emotional picture. Participants were 29 patients with schizophrenia and 31 healthy controls. The Positive and Negative Syndrome Scale (PANSS) and the Scale of Social Function in Psychosis Inpatients (SSPI) were used to assess symptoms and social functioning. In total, patients with schizophrenia showed significantly fewer fixations, saccades numbers and decreased fixations in areas of interest. As expected, patients showed shorter scanpath length, but only in the pictures with social settings. Furthermore, the effect size of scanpaths parameters under social scene was all greater than isolated face. In addition, patients compared to controls showed more abnormal scanpath parameters processing negative and neutral faces than positive faces, especially in social scene. The present study suggests that scanpath length for social scene faces may be more sensitive than for isolated face pictures. Our findings further support restricted scanpath whilst recognizing emotional facial expressions in natural social scenes as a favorable topic for further investigation as a trait marker.

Altered resting-state functional connectivity of the insula in individuals with clinical high-risk and patients with first-episode schizophrenia.

OBJECTIVES: Abnormalities in insular functional connectivity have been implicated in many clinical features of schizophrenia. The aim of this study was to determine to what degree such abnormalities occur in individuals with clinical high risk for psychosis (CHR), and whether which is associated with symptom severity. METHODS: Resting-state fMRI data were collected from 47 healthy controls, 24 CHR individuals and 19 patients with first-episode schizophrenia. Using the posterior, dorsal and ventral insular subregions as separate seeds, we examined resting-state functional connectivity differences between different groups and the association between concurrent symptom severity and dysconnectivity. RESULTS: Compared with healthy controls, both CHR individuals and schizophrenia patients showed hypoconnectivity between posterior insula (PI) and somatosensory areas, and between dorsal anterior insula (dAI) and putamen. Schizophrenia patients also showed dAI and ventral anterior insula(vAI) hyperconnectivity with visual areas relative to controls and CHR individuals. Correlation analysis revealed that dAI functional connectivity with superior temporal gyrus was positively correlated with positive symptoms of CHR, and vAI connectivity with dorsolateral prefrontal cortex was negatively correlated with the severity of the symptoms of first-episode schizophrenia. CONCLUSIONS: Our findings suggest that insular functional dysconnectivity with the sensory cortex may be a system-level neural substrate preceding the onset of psychosis.

The effect of left-behind phenomenon and physical neglect on behavioral problems of children.

OBJECTIVE: Left-behind children have a high incidence of behavioral problems in some Eastern countries, especially China. We sought to assess the combined effects of physical neglect, a major embodiment of the left-behind phenomenon, and the trauma of being left behind on subsequent behavioral problems. METHOD: 776 children (including 600 left-behind children) aged 12-16 years were chosen by cluster sampling in rural China. The Childhood Trauma Questionnaire-Short Form and the Conners Teacher Rating Scale were used to evaluate physical neglect and behavioral problems. RESULTS: Left-behind children experienced more physical neglect (mean difference = 0.63; 95%CI 0.15-1.10; P = 0.01) and were more inattentive (mean difference=0.11; 95%CI 0.03-0.19; P = 0.009) than non-left-behind children. Physically neglected left-behind children had higher scores for conduct problems, inattention, and hyperactivity index than non-left-behind without physical neglect group (P < 0.05 for each). Among left-behind children, physical neglect group had significantly more conduct problems than those of controls (mean difference=0.14; 95%CI 0.05-0.23; P = 0.008). Physically neglected non-left-behind children had higher scores for conduct problems than those of left-behind children without physical neglect (mean difference=0.31; 95%CI 0.13-0.47; P = 0.003). Among physically neglected children, left-behind children had significantly higher scores for inattention than those of non-left-behind children (mean difference=0.13; 95%CI 0.04-0.22; P = 0.037). CONCLUSION: Left-behind children have more behavioral problems than non-left-behind children. Physical neglect may result in more severe conduct problems than those associated with staying behind, and staying behind may lead to inattention. Exposure to both may lead to more obvious behavioral problems. Therefore, we should accord more attention to physically neglected and left-behind children.

Impact of childhood trauma on sensory gating in patients with first-episode schizophrenia.

BACKGROUND: Childhood trauma (CT) has been found to contribute to the onset of schizophrenia and auditory sensory gating deficit is a leading endophenotype for schizophrenia. However, the association between the CT and sensory gating in first-episode schizophrenia remains elusive. METHODS: Fifty-six patients and 49 age and sex-matched healthy controls were assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) for CT and Positive and Negative Syndrome Scale (PANSS) for symptoms severity. Sensory gating was tested using the modified paradigm, perceived spatial separation-induced prepulse inhibition (PSS-PPI), and the perceived spatial co-location PPI (PSC-PPI or classical PPI). RESULTS: Comparing with healthy controls, the patients had significantly higher score on sexual abuse (t = 2.729, p < 0.05), lower PSS- PPI, % (ISI = 120 ms and ISI = 60 ms) (t = - 3.089, - 4.196, p < 0.05). Univariate analysis revealed the absence of a significant correlation among CT, PPI paradigms and symptoms. However, multiple linear regression analyses demonstrated the CTQ-SF total was negatively associated with PSS PPI (ISI = 120 ms) (p = 0.018). CONCLUSION: The current study illustrates that the impact of CT on sensory gating in patients with first-episode schizophrenia, and thus we conclude that CT may be a risk factor to the occurrence of schizophrenia through its impact on sensory gating.

Ischemic injury underlies the pathogenesis of aristolochic acid-induced acute kidney injury.

Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial renal disease caused by aristolochic acid intake. To determine the contribution of renal ischemia to the pathogenesis of AAN, we characterized changes in the expression of angiogenic factors and vasoactive substances, and then we evaluated the expression of a marker of hypoxia in an acute AAN rat model. Rats were orally administrated either a decoction of Aristolochiae manshuriensis that contained 20 mg/kg of aristolochic acid-I or an equal volume of distilled water (control group) once daily for 4 days or 7 days. Renal histology and serum creatinine were assessed. Expression of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1alpha) mRNA within renal cortex were determined by semiquantitative reverse-transcription polymerase chain reaction. Levels of ET-1, nitric oxide (NO), vascular endothelial growth factor (VEGF), and HIF-1alpha in kidneys were determined by radioimmunoassay, Griess method, Western blot, and immunohistochemistry, respectively. Tubular injury scores and ET-1 mRNA expression were increased in the AA-treated rats at both days 4 and 8, whereas serum creatinine level and ET-1 protein expression was increased only at day 4. In contrast, NO production in AA-treated rats was decreased at day 8 compared with the control group. Similarly, VEGF protein expression was reduced in the AA-treated rats at both days 4 and 8. A dramatic increase in nuclear staining for HIF-1alpha was observed mainly in the tubular cells of tubulointerstitial damage area in the AA-treated rats at day 8. The observed increase in HIF-1alpha protein expression, decrease in VEGF protein expression, and imbalance of vasoactive substances after induction of acute kidney injury by AA suggests that ischemic injury contributes to the pathogenesis of AAN.

Cytotoxicity of phenanthrenes extracted from Aristolochia contorta in human proximal tubular epithelial cell line.

BACKGROUND/AIMS: Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is predominantly a result of aristolochic acid I (AA-I) intoxication. However, other unidentified phytotoxins have indeed been postulated as the cause of this unique interstitial nephropathy. The purpose of this study was to investigate the cytotoxicity of other phenanthrene derivatives extracted from Aristolochia contorta in the human proximal tubular epithelial cell line HK-2. METHODS: After HK-2 cells were incubated with an indicated concentration of test compounds for 24 h, cell viability was assessed by lactate dehydrogenase (LDH) leakage assay (cell membrane damage) in combination with MTT assay (metabolic capability). Cellular morphologic assessments were performed with a phase-contrast inverted microscope and transmission electron microscope. RESULTS: In all test compounds at 5 microg/ml, AA-I, 7-methoxy-aristololactam IV and aristololactam IVa showed cytotoxic activity in HK-2 cells in both MTT assay and LDH leakage assay (p < 0.01). At high concentration (5-80 microg/ml), these three compounds caused a dose-dependent decrease in MTT reduction and a dose-dependent increase in LDH leakage compared to non-treated cells (p <0.01). In LDH leakage assay, 40 mug/ml 7-methoxy-aristololactam IV induced a 1.58-fold LDH leakage compared to AA-I at the same concentration (p < 0.01). Moreover, the IC50 of these three compounds were 16.675 microg/ml for AA-I, 4.535 microg/ml for 7-methoxy-aristololactam IV, and 30.244 microg/ml for aristololactam IVa in MTT assay. The cellular morphologic assessments suggest interactions with cell membrane and intracellular structures such as lysosome and mitochondria are likely to be involved in cell injury induced by these three compounds. CONCLUSION: The potency of cytotoxic activity of aristololactam IVa and 7-methoxy-aristololactam IV extracted from A. contorta is similar to or even stronger than that of AA-I.