Dynamic regulation of phosphorylation of NMDA receptor GluN2B subunit tyrosine residues mediates ketamine rapid antidepressant effects.

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyr1472NR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses. The dynamic regulation of phosphorylation of NR2B provides a new perspective for developing new antidepressant strategies.

Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation.

Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota-brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the "SD microbiota" into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored "SD microbiota" also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.

Spatio-temporal dynamics of EEG features during sleep in major depressive disorder after treatment with escitalopram: a pilot study.

BACKGROUND: Previous studies have shown escitalopram is related to sleep quality. However, effects of escitalopram on dynamics of electroencephalogram (EEG) features especially during different sleep stages have not been reported. This study may help to reveal pharmacological mechanism underlying escitalopram treatment. METHODS: The spatial and temporal responses of patients with major depressive disorder (MDD) to escitalopram treatment were analyzed in this study. Eleven MDD patients and eleven healthy control subjects who completed eight weeks' treatment of escitalopram were included in the final statistics. Six-channel sleep EEG signals were acquired during sleep. Power spectrum and nonlinear dynamics were used to analyze the spatio-temporal dynamics features of the sleep EEG after escitalopram treatment. RESULTS: For temporal dynamics: after treatment, there was a significant increase in the relative energy (RE) of Î´1 band (0.5 - 2 Hz), accompanied by a significant decrease in the RE of ß2 band (20 - 30 Hz). Lempel-Ziv complexity and Co - complexity values were significantly lower. EEG changes at different sleep stages also showed the same regulation as throughout the night sleep. For spatio dynamics: after treatment, the EEG response of the left and right hemisphere showed asymmetry. Regarding band-specific EEG complexity estimations, δ1 and ß2 in stage-1 and δ1 in stage-2 sleep stage in frontal cortex is found to be much more sensitive to escitalopram treatment in comparison to central and occipital cortices. CONCLUSIONS: The sleep quality of MDD patients improved, EEG response occurred asymmetry in left and right hemispheres due to escitalopram treatment, and frontal cortex is found to be much more sensitive to escitalopram treatment. These findings may contribute to a comprehensive understanding of the pharmacological mechanism of escitalopram in the treatment of depression.

BDNF-GSK-3ß-ß-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects of Morinda officinalis Oligosaccharides in Rats.

Background: Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear. Methods: Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3ß in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3ß, ß-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot. Results: We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3ß by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3ß, and ß-catenin in the medial prefrontal cortex. Conclusion: Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress.

Effects of environmental stress on the depression-like behaviors and the diurnal rhythm of corticosterone and melatonin in male rats.

Environmental stress (ES) is commonly used in producing chronic unpredictable mild stress to study pathogenesis of depression, including the regulatory role of circadian system on depression. However, the direct effect of ES on the circadian system has been rarely explored. The present study was aimed to investigate the effect of ES on depression-like behaviors and diurnal rhythm of plasma hormone/peptide levels in male rats. Rats were allocated into control group (CON group), low frequency ES group (LF group) and high frequency ES group (HF group). Sucrose preference test (SPT), open field test (OFT), weight gain, food and water intake were conducted to assess depression- and anxiety-like behaviors. A total of 7 times of the tail venous blood was collected with an interval of 4 h during 24 h from other rats who subjected to the same procedures of ES but not the behavioral tests. The alterations of diurnal rhythm of peripheral plasma corticosterone (CORT) and melatonin, and changes of the cholecystokinin (CCK), neuropeptide Y and leptin levels at zeitgeber time (ZT) 0 were detected by using enzyme-linked immunosorbent assay (ELISA). We found that ES led to a disturbance of diurnal rhythm of CORT and melatonin in the plasma. Besides, it also increased plasma leptin level and decreased body weight gain, but it did not produce depression- and anxiety-like behaviors compared with those rats in the control group. In short, our findings indicated that the ES could induce a disturbance of diurnal rhythm of plasma CORT and melatonin in male rats.

Mitochondrial DNA copy number, but not haplogroup is associated with keratoconus in Han Chinese population.

Oxidative stress may play a role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and variations may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. To test whether mtDNA background and copy number confer genetic susceptibility to KC in the Han Chinese population, we performed this association study. We analyzed mtDNA sequence variations in 210 KC patients and 309 matched individuals from China, and classified each subject by haplogroup. Mitochondrial DNA copy number was measured in a subset of these subjects (193 patients and 103 controls). Comparison of matrilineal components of the cases and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that KC patients had significantly lower mtDNA copy numbers than controls (P = 0.0002), even when age, gender, and mtDNA background were considered. Our results suggest that mtDNA copy number, but not haplogroup, is associated with keratoconus, and may contribute to its pathogenesis.

Role of the NMDA receptor in cognitive deficits, anxiety and depressive-like behavior in juvenile and adult mice after neonatal dexamethasone exposure.

Postnatal dexamethasone (DEX) therapy has been used to treat or prevent chronic lung disease after premature births. However, there are many reports of long-term negative neurodevelopmental sequelae following this treatment. In contrast, hydrocortisone (HYD), which has fewer neurodevelopment adverse effects, is used as an alternative for DEX. In this study, we report that neonatal DEX exposure (days 1-3) caused alterations of amino acids affecting N-methyl-d-aspartate (NMDA) receptor neurotransmission in mouse brains. Neonatal DEX, but not HYD, exposure (days 1-3) significantly decreased the GluN2B subunit of NMDA receptor in the hippocampus at juvenile and adult stages. Mice treated with DEX showed cognitive deficits, as well as anxiety and depressive-like behavior at juvenile and adult stages. In contrast, mice treated with HYD (days 1-3) showed no behavioral abnormalities at these stages. In the DEX suppression test, plasma levels of corticosterone in mice exposed neonatally to DEX and HYD were significantly higher at juvenile, but not adult stages. Pretreatment with Ro 63-1908, an antagonist at GluN2B subunit, 30min before each injection of DEX, prevented cognitive deficits, as well as anxiety and depressive-like behavior in juvenile and adult mice. Interestingly, subsequent repeated (days 29-33) administration of Ro 63-1908 or L701324, an antagonist of the glycine modulatory site on the NMDA receptor, significantly suppressed behavioral abnormalities in juvenile and adult mice after neonatal DEX exposure. These results indicate that neonatal DEX, but not HYD, exposure produced behavioral abnormalities in juvenile and adult mice by altering glutamatergic neurotransmission via the NMDA receptor. The NMDA receptor antagonists may prevent or treat these DEX-induced neonatal behavioral abnormalities in later life.

Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms contribute to bladder cancer risk: a meta-analysis.

Numerous epidemiological studies have been conducted to investigate the association between Xeroderma pigmentosum complementation group D (XPD) Asp312Asn (rs1799793 G > A) and Lys751Gln (rs13181 A > C) polymorphisms and bladder cancer risk; however, the conclusions remain controversial. With this in mind, we performed this meta-analysis with 11 studies including 3,797 cases and 5,094 controls for Asp312Asn and 21 studies including 6,360 cases and 7,894 controls for Lys751Gln polymorphism. We searched available literatures from PubMed, Embase, and CBM databases. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. Moreover, to validate biological plausibility of our findings, the effects of these two polymorphisms on XPD gene expression within three ethnicities was determine by gene expression analysis based on imputed genotypes from HapMap. Overall, the variant allele of Asp312Asn polymorphism was associated with an increased risk of bladder cancer (Asn/Asn vs. Asp/Asp: OR = 1.51, 95% CI = 1.19-1.91; Asp/Asn vs. Asp/Asp: OR = 1.23, 95% CI = 1.12-1.35; recessive model: OR = 1.33, 95% CI = 1.10-1.61; dominant model: OR = 1.32, 95% CI = 1.14-1.52; and allele comparing: OR = 1.26, 95% CI = 1.11-1.42). We found the Lys751Gln was associated with increased bladder cancer risk only under the recessive model (OR = 1.14, 95% CI = 1.01-1.29). Stratification analyses demonstrated an increased risk for Asians and hospital-based studies under all genetic models while only under the dominant model for Caucasians as to the Asp312Asn polymorphism and for Caucasians under the recessive model as to the Lys751Gln polymorphism. We also found the Asp312Asn polymorphism can significantly influence mRNA expression levels among Asians and Caucasians, and the Lys751Gln polymorphism has a similar effect for Caucasians. Despite some limitations, this meta-analysis suggests that polymorphisms in XPD gene may contribute to bladder cancer susceptibility. These findings need further validation by large well-designed prospective studies.

Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), signaling represent potential therapeutic targets for major depressive disorder. The purpose of this study is to examine whether TrkB ligands show antidepressant effects in an inflammation-induced model of depression. METHODS: In this study, we examined the effects of TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and TrkB antagonist ANA-12 on depression-like behavior and morphological changes in mice previously exposed to lipopolysaccharide (LPS). Protein levels of BDNF, phospho-TrkB (p-TrkB), and TrkB in the brain regions were also examined. RESULTS: LPS caused a reduction of BDNF in the CA3 and dentate gyrus (DG) of the hippocampus and prefrontal cortex (PFC), whereas LPS increased BDNF in the nucleus accumbens (NAc). Dexamethason suppression tests showed hyperactivity of the hypothalamic-pituitary-adrenal axis in LPS-treated mice. Intraperitoneal (i.p.) administration of 7,8-DHF showed antidepressant effects on LPS-induced depression-like behavior, and i.p. pretreatment with ANA-12 blocked its antidepressant effects. Surprisingly, ANA-12 alone showed antidepressant-like effects on LPS-induced depression-like behavior. Furthermore, bilateral infusion of ANA-12 into the NAc showed antidepressant effects. Moreover, LPS caused a reduction of spine density in the CA3, DG, and PFC, whereas LPS increased spine density in the NAc. Interestingly, 7,8-DHF significantly attenuated LPS-induced reduction of p-TrkB and spine densities in the CA3, DG, and PFC, whereas ANA-12 significantly attenuated LPS-induced increases of p-TrkB and spine density in the NAc. CONCLUSIONS: The results suggest that LPS-induced inflammation may cause depression-like behavior by altering BDNF and spine density in the CA3, DG, PFC, and NAc, which may be involved in the antidepressant effects of 7,8-DHF and ANA-12, respectively.

Heterologous overexpression of Vigna radiata epoxide hydrolase in Escherichia coli and its catalytic performance in enantioconvergent hydrolysis of p-nitrostyrene oxide into (R)-p-nitrophenyl glycol.

Two native epoxide hydrolases (EHs) were previously discovered from mung bean powder (Vigna radiata), both of which can catalyze the enantioconvergent hydrolysis of p-nitrostyrene oxide (pNSO). In this study, the encoding gene of VrEH1 was successfully cloned from the cDNA of V. radiata by RT-PCR and rapid amplification of cDNA ends (RACE) technologies. High homologies were found to two putative EHs originated from Glycine max (80%) and Medicago truncatula (79%). The vreh1 gene constructed in pET28a(+) vector was then heterologously overexpressed in Escherichia coli BL21(DE3), and the encoded protein was purified to homogeneity by nickel affinity chromatography. It was shown that VrEH1 has an optimum activity at 45 °C and is very thermostable with an inactivation energy of 468 kJ mol(-1). The enzyme has no apparent requirement of metal ions for activity, and its activity was strongly inhibited by 1 mM of Ni(2+), Cu(2+), Fe(2+), or Co(2+). By adding 0.1% Triton X-100, the enzyme activity could be significantly increased up to 340%. VrEH1 shows an unusual ability of enantioconvergent catalysis for the hydrolysis of racemic pNSO, affording (R)-p-nitrophenyl glycol (pNPG). It displays opposite regioselectivity toward (S)-pNSO (83% to Cα) in contrast to (R)-pNSO (87% to Cß). The K M and k cat of VrEH1 were determined to be 1.4 mM and 0.42 s(-1) for (R)-pNSO and 5.5 mM and 6.2 s(-1) for (S)-pNSO. This thermostable recombinant VrEH1 with enantioconvergency is considered to be a promising biocatalyst for the highly productive preparation of enantiopure vicinal diols and also a good model for understanding the mechanism of EH stereoselectivity.

Glycogen synthase kinase-3ß in the ventral tegmental area mediates diurnal variations in cocaine-induced conditioned place preference in rats.

Cocaine sensitization and reward are reported to be under the influence of diurnal rhythm. However, no previous studies have reported brain areas that play a role as modulators and underlie the mechanism of diurnal variations in cocaine reward. We examined (1) the diurnal rhythm of glycogen synthase kinase-3ß (GSK-3ß) activity in the suprachiasmatic nucleus (SCN) and reward-related brain areas in naive rats; (2) the effect of day and night on the acquisition of cocaine-induced conditioned place preference (CPP); (3) the influence of cocaine-induced CPP on GSK-3ß activity in the SCN and reward-related brain areas; and (4) the effect of the GSK-3ß inhibitor SB216763 microinjected bilaterally into the ventral tegmental area (VTA) on cocaine-induced CPP. A significant diurnal rhythm of GSK-3ß activity was found in the SCN and reward-related brain areas, with diurnal variations in cocaine-induced CPP. GSK-3ß activity in the SCN and reward-related brain areas exhibited marked diurnal variations in rats treated with saline. GSK-3ß activity in rats treated with cocaine exhibited distinct diurnal variations only in the prefrontal cortex and VTA. Cocaine decreased the expression of phosphorylated GSK-3ß (i.e. increased GSK-3ß activity) only in the VTA in rats trained and tested at ZT4 and ZT16. SB216763 microinjected into the VTA bilaterally eliminated the diurnal variations in cocaine-induced CPP, but did not affect the acquisition of cocaine-induced CPP. These findings suggest that the VTA may be a critical area involved in the diurnal variations in cocaine-induced CPP, and GSK-3ß may be a regulator of diurnal variations in cocaine-induced CPP.

Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis.

Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022. The primary outcome was the mean change in the total score for different mental disorders. The secondary outcome was the odds ratio (OR) of response, remission rates and risk ratio (RR) of adverse events (AEs). A total of 181 studies (N = 65,480) were included. All SGAs showed significant effects in treating other mental disorders compared with placebo, except autistic disorder and dementia. Aripiprazole is the most effective treatment for bipolar mania [effect size = -0.90, 95% CI: -1.59, -0.21] and Tourette's disorder [effect size = -0.80, 95% CI: -1.14, -0.45], olanzapine for bipolar depression [effect size = -0.86, 95% CI: -1.32, -0.39] and post-traumatic stress disorder [effect size = -0.98, 95% CI: -1.55, -0.41], lurasidone for depression [effect size = -0.66, 95% CI: -0.82, -0.50], quetiapine for anxiety [effect size = -1.20, 95% CI: -1.96, -0.43], sleep disorders [effect size = -1.2, 95% CI: -1.97, -0.58], and delirium [effect size = -0.36, 95% CI: -0.70, -0.03], and risperidone for obsessive-compulsive disorder [effect size = -2.37, 95% CI: -3.25, -1.49], respectively. For safety, AE items for each SGAs was different. Interestingly, we found that some AEs of OLZ, QTP, RIS and PALI have significant palliative effects on some symptoms. Significant differences in the efficacy and safety of different SGAs for treatment of other mental disorders should be considered for choosing the drug and for the balance between efficacy and tolerability for the specific patient.

Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Effects of bilateral repetitive transcranial magnetic stimulation on prospective memory in patients with schizophrenia: A double-blind randomized controlled clinical trial.

AIMS: To investigate effects of repetitive transcranial magnetic stimulation (rTMS) on the prospective memory (PM) in patients with schizophrenia (SCZ). METHODS: Fifty of 71 patients completed this double-blind placebo-controlled randomized trial and compared with 18 healthy controls' (HCs) PM outcomes. Bilateral 20 Hz rTMS to the dorsolateral prefrontal cortex at 90% RMT administered 5 weekdays for 4 weeks for a total of 20 treatments. The Positive and Negative Symptom Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and PM test were assessed before and after treatment. RESULTS: Both Event-based PM (EBPM) and Time-based PM (TBPM) scores at baseline were significantly lower in patients with SCZ than that in HCs. After rTMS treatments, the scores of EBPM in patients with SCZ was significantly improved and had no differences from that in HCs, while the scores of TBPM did not improved. The negative symptom scores on PANSS and the scores of almost all subscales and total scores of SANS were significantly improved in both groups. CONCLUSIONS: Our findings indicated that bilateral high-frequency rTMS treatment can alleviate EBPM but not TBPM in patients with SCZ, as well as improve the negative symptoms. SIGNIFICANCE: Our results provide one therapeutic option for PM in patients with SCZ.

Depression and alterations in hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axis function in male abstinent methamphetamine abusers.

The present study was to investigate depression and alterations in the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis function in methamphetamine (METH) abusers after abstinence. Depression was assessed using the 13-item Beck Depression Inventory (BDI-13) scale; blood samples from in-patients who were METH abusers and age-matched and sex-matched healthy controls were collected. The demographic characteristics and history of METH abuse also was assessed. We found that serum levels of adrenocorticotropic hormone (ACTH) and thyroxine were increased; and serum levels of cortisol, triiodothyronine, and thyroid-stimulating hormone were decreased; and the BDI score was higher in METH abusers compared with control. In addition, there was no correlation between the BDI-13 score and any of hormones of HPA and HPT axis was found. Particularly, we found abnormally higher ACTH level and mismatched with lower cortisol level in abstinent METH abusers. These results indicate that METH abusers and that their HPA and HPT functions are all altered after abstinence. Chronically using METH may destroy the regulatory function of the HPA axis, especially the feedback regulation of cortisol to ACTH.

[Impact of intrauterine device insertion surgery on women's mental state].

OBJECTIVE: To evaluate the impact of the intrauterine device (IUD) insertion on the mental state of women. METHODS: From Jan. 2009 to Jun. 2010, a multi-center clinical observational study was performed. Totally 641 women were selected in the six provinces' 18 family planning service stations and hospitals for IUD insertion surgery study. Analysis of the change of women's mental state which was evaluated by symptom checklist-90 (SCL-90) scale before and after IUD insertion surgery. RESULTS: Before and after IUD insertion surgery, 10 factors' scores in SCL-90 of the observed objects were between 1.1 to 1.2, total scores were 107±27 and 105±25, respectively. Before and after surgery, total average score both were 1.2, the average score of positive items both were 2.1. The difference of the above results were not statistically significance (all P>0.05). Preoperative and postoperative, the rate of positive items was 9.2%-19.6% and 7.7%-17.6%, respectively.In addition to anxiety and fear, the rate of other factors' positive items postoperative was significantly lower than those in the preoperative (all P<0.05). The incidence of the observed objects postoperative of each factor score, "deteriorated" was in the range of 4.9% to 23.0%, "improved" was in the range of 26.3%-50.1%. The incidence of total scores, "deterioration" was 28.8% (166/575), "improved" was 45.6% (262/575). The incidence of the average score of positive items, "deterioration" was 3.7% (21/575), "improved" was 52.3% (301/575). Logistic analysis showed that, in addition to unit level, there were no other significant influencing factors for women' mental state of postoperative (all P>0.05). CONCLUSION: IUD insertion surgery has no adverse effect on women's mental state.

[Aetiology analyses of 334 cases fungal keratitis].

OBJECTIVE: To analyze the distribution of pathogenic bacterium of the fungal keratitis patients for providing the data of clinical diagnosis and treatment. METHODS: From July 2005 to December 2010 in Shandong Eye Hospital there were 352 smears of corneal ulcers and corneal tissue exemplar removed in surgery from fungal keratitis patients. The all exemplars were cultured with the Sabouraud dextrose agar culture media in 28°C under the humidor for 7 days. The strains was identified according to the appearance of fungal colonies, mycelium, spore shape, spore arrangement and fungal shape. And there did the retrospective analyses about the positive rate of fungal culture, genus distribution, seasonal distribution and sources of patients, sex ratio, age distribution and occupation. etc. RESULTS: There were 334 stock positive fungal culture in 352 cultured specimens from fungal corneal ulcers, the positive rate was 94.9%. There were 187 positive culture from 203 corneal scraping exemplars, the positive rate was 92.1%; there were 147 positive culture from 149 corneal tissue removed in surgery, the positive rate was 98.7%. The Fusarium strains was most common in all isolated strain, 211 (63.2%). The Aspergillus was secondly 47 (14.1%). The character of seasonal distribution of culture positive strain: the 48 strains (14.4%) were cultivated from January to March; the 48 strains (14.4%) were cultivated from April to June; the 64 strains were cultivated (19.2%) from July to September; the 174 strains (52.0%) were cultured from October to December, the ratio were 1:1:1.3:3.6 quarterly (χ(2) = 3.360, P = 0.339). The incidence of fungal keratitis were higher in the autumn and winter than in spring and summer. The ratio of the male and the female was 2.04:1 in 334 culture-positive patients; the mean age was (48 ± 22) years old. The 217(65%) came from farmer in the developed group, and the other 117 cases came from other occupations (35%). The 289 (87%) cases came from Shandong Province in 334 positive patients, the 45 cases (13%) came from other province of Province. Chi-square test method was used to analysis the differences of incidence of fungal keratitis among the four seasons using SPSS11.5. CONCLUSIONS: The Fusarium is the most important pathogen in fungal keratitis in Shandong Province. The high positive culture rate of fungal keratitis specimens plays an important role in clinical diagnosis and treatment.

[Preliminary clinical results of deep anterior lamellar keratoplasty in the treatment deep infectious purulent keratitis].

OBJECTIVE: To evaluate the clinical results of deep anterior lamellar keratoplasty (DALK) assisted by big bubble technique in the treatment of deep infectious purulent keratitis. METHODS: Seventeen patients (17 eyes) with deep infectious purulent keratitis received DALK surgery in Shandong Eye Hospital from January 2011 to March 2012. Case selection:Patients with purulent keratitis, the infection or infiltrate depth was more than four fifth corneal thickness; SURGICAL TECHNIQUE: Use DALK assisted by big bubble technique to cut off the lesions and expose the Descemet's membrane. The prepared donor which stored in D-X medium or in glycerine preoperatively was oversized by 0.25 mm, and after stripping of Descemet's membrane, the donor button was interrupted sutured with 10-0 nylon suture. The perioperative complications, recurrence, graft status and visual recovery were evaluated. RESULTS: The mean follow up time were 9 months.17 patients with average age of (46 ± 13) year old received DALK surgery, including 14 cases of fungal keratitis and 3 cases of bacteria keratitis. Perioperative complications:Two cases suffered micro perforation and were continuing performed DALK surgery after injecting air bubble in the anterior chamber. Three cases suffered double anterior chamber, one was resolved after graft resuture, and the other two were absorbed automatically.One patient suffered fungal recurrence and cured with secondary penetrating keratoplasty. Graft status:All grafts attached closely to the recipients, slit lamp and AS-OCT examinations were difficult to distinguish the interface. All of grafts were transparent. Visual acuity:before the operation best corrected visual acuity (BCVA) in patients with HM/20 cm to 3.7, after the surgery patients' BSCVA improved to 4.5-5.0. The mean astigmatism postoperatively of 16 cases received successful DALK finally was (4.53 ± 2.35) D . CONCLUSIONS: For patients with deep infectious purulent keratitis, big bubble technique assistants DALK surgery is still a safe and effective method.

Development of sensory integration therapy in Mainland China: A comprehensive study with bibliometrics and visualization techniques.

Sensory integration therapy (SIT) is an intervention to improve the developmental and learning problems in children. It was introduced in China from late 1980 s to early 1990 s and has received considerable attention from scholars. However, due to its late development in China and its specialised nature, it is worth exploring in depth whether it is recognized by the general public and how it is researched by academics. Therefore, we used Internet survey approach to explore the actual feedback of users towards SIT through the Internet. At the same time, bibliometric method and visualization techniques were used to study 892 journal articles on SIT in CNKI, Wanfang Database and VIP Database to analyze the spatial and temporal distribution, subject distribution, keyword co-occurrence, and keyword clustering of SIT research in mainland China since it came to China mainland. We found that the research on SIT in mainland China has been fruitful. However, the public is less aware of its basic function, therapeutic effects, and necessity. Our findings point to the need to raise awareness of sensory integration disorder and sensory integration therapy among the general public, and to strengthen academic research on sensory integration therapy.

Association between thyroid autoimmunity and clinical characteristics in first-episode and drug-naive depressed patients with suicide attempts.

BACKGROUND: Previous reports had linked depression to thyroid function. However, the relationship between thyroid function and clinical characteristics in major depressive disorder (MDD) patients with suicidal attempts (SA) is still unclear. AIMS: This study aims to reveal the association between thyroid autoimmunity and clinical characteristics in depressed patients with SA. METHODS: We divided 1718 first-episode and drug-naive MDD patients into groups with suicide attempt (MDD-SA) and without suicide attempt (MDD-NSA). Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) were assessed; thyroid function and autoantibodies were detected. RESULTS: The total scores of HAMD, HAMA and psychotic positive symptoms were significantly higher in patients with MDD-SA, accompanied by higher levels of TSH, TG-Ab and TPO-Ab, than in patients with MDD-NSA, without gender differences. Total scores of positive symptoms (TSPS) in MDD-SA patients with increased TSH or TG-Ab was significantly higher than in MDD-NSA patients and in MDD-SA patients with normal TSH and TG-Ab. The proportion of elevated-TSPS in MDD-SA patients was >4 times that in MDD-NSA patients. The proportion of MDD-SA patients with elevated-TSPS was >3 times that with not-elevated TSPS patients. CONCLUSIONS: Thyroid autoimmune abnormalities and psychotic positive symptoms may be the clinical features of MDD-SA patients. Psychiatrists should be more alert to the possibility of suicidal behaviors when they first encounter such a patient.