Anxiolytic and Anti-depressive Like Effects of Translocator Protein (18 kDa) Ligand YL-IPA08 in a Rat Model of Postpartum Depression.

Translocator protein 18 kDa (TSPO) is mainly distributed in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. It mediates cholesterol transportation across the phospholipid membrane, which is a prerequisite for neurosteroid synthesis. Though the ligand of TSPO has clinical value in the diagnosis and treatment of neuropsychiatric disorders, the pharmacological study of TSPO for anti-postpartum depression has not been reported. In this study, the classical method of reproductive hormone withdrawal was used to construct a rat model of postpartum depression (PPD). The effect of YL-IPA08, a new ligand compound of TSPO, on PPD was evaluated using multiple behavioral tests at progressive time points. Additionally, real-time quantitative PCR, Western-blotting and an enzyme linked immunosorbent assay were conducted to elucidate the potential molecular mechanism of such effect. We report that the levels of TSPO and neurosteroids in the hippocampus and prefrontal cortex were significantly decreased in PPD rats compared to healthy controls. After 3 weeks of drug treatment, the levels of TSPO and neurosteroids in the hippocampus of PPD rats were increased, and anxiety and depressive like behaviors were alleviated. Meanwhile, compared with sertraline treatment, a positive control in this study, YL-IPA08 treatment had a shorter onset time. Our results suggest that the anxiolytic and anti-depressive activity of YL-IPA08 has significant value in the treatment of PPD and that TSPO may be a potential new target for the treatment of PPD.

Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment.

BACKGROUND AND AIMS: Postoperative delirium (POD) is a common and serious surgical complication among the elderly, especially in those with amnestic mild cognitive impairment (aMCI). Dexmedetomidine (DEX) is neuroprotective for delirium. In this study, we determined the effect of intravenously administered DEX during general anesthesia on POD in elderly aMCI patients undergoing elective hip joint or knee joint or shoulder joint replacement surgery. METHODS: This was a prospective, randomized parallel-group study of aMCI (n = 80) and normal elderly patients (n = 120). Prior to surgery, all subjects underwent neuropsychological assessment and were assigned to one of four groups: the aMCI DEX group (MD group, n = 40), the aMCI normal saline group (MN group, n = 40), the control DEX group (CD group, n = 60), and the control normal saline group (CN group, n = 60). The confusion assessment method was used to screen POD on postoperative days 1, 3, and 7. RESULTS: We found patients age was positively correlated with POD incidence in the MN group (p < 0.05) but not in the CN group (p < 0.05). DEX treatment significantly decreased POD incidence in both control and aMCI groups relative to their respective placebo groups (all p < 0.05). The fraction of patients whose normal cognitive function was not restored by day 7 after surgery was significantly higher in the MN group than the MD and CN groups (all p < 0.05). CONCLUSIONS: These findings suggested that DEX treatment during surgery significantly reduced POD incidence in both normal and aMCI elderly patients, suggesting that it may be an effective option for the prevention of POD.

Correlation of Obesity and Clinical Characteristics in Drug-Naive First-Episode Patients With Schizophrenia.

OBJECTIVES: This study was aimed at investigating the prevalence of obesity in drug-naive first-episode (DNFE) patients with schizophrenia and its association with metabolic parameters, psychopathological symptoms, and cognitive function. METHODS: We collected general information on 411 DNFE schizophrenia patients and divided them into obese and nonobese groups according to body mass index (BMI). Glucolipid metabolic parameters of patients were collected. Positive and Negative Syndrome Scale was performed for assessing patients' psychopathological symptoms. Cognitive function was observed and evaluated in both groups. Pearson correlation analysis was applied to assess factors related to BMI, while we conducted multiple stepwise regression analysis for determining risk factors for obesity. RESULTS: Obesity occurred in 60.34% of DNFE patients with schizophrenia, whereas the obese group had notably higher BMI value and waist-to-hip ratio than the nonobese group ( P < 0.05). Obese patients had markedly higher levels of blood glucose, insulin, apolipoprotein B, total triglycerides, low-density lipoprotein cholesterol, and total cholesterol versus nonobese patients ( P < 0.05). Besides, the disease severity and cognitive function were dramatically lower in the obese group. Results of multiple stepwise regression analysis demonstrated negative symptoms, low-density lipoprotein cholesterol, triglycerides, and blood glucose levels as the risk factors for comorbid obesity in DNFE patients with schizophrenia. CONCLUSIONS: The detection rate of obesity was high in DNFE patients with schizophrenia, and there was an intrinsic association between obesity and glucolipid metabolism, clinical symptoms, and cognitive function among them. Our study will provide a theoretical foundation for the diagnosis of obesity in DNFE patients with schizophrenia and the development of effective early interventions.

Priority conservation area of Larix gmelinii under climate change: application of an ensemble modeling.

Larix gmelinii (Rupr.) Kuzen is a major tree species with high economic and ecological value in the Greater Khingan Mountains coniferous forest of Northeast China. Reconstructing the priority Conservation Area of Larix gmelinii under Climate could provide a scientific basis for its germplasm conservation and management. The present study used ensemble and Marxan model simulations to predict species distribution areas and delineate priority conservation areas for Larix gmelinii in relation to productivity characteristics, understory plant diversity characteristics, and climate change impacts. The study revealed that the Greater Khingan Mountains and the Xiaoxing'an Mountains, with an area of approximately 300 974.2 km2, were the most suitable for L. gmelinii. The stand productivity of L. gmelinii in the most suitable area was significantly higher than that in the less suitable and marginally suitable areas, but understory plant diversity was not dominant. The increase in temperature under future climate change scenarios will reduce the potential distribution and area under L. gmelinii; the species will migrate to higher latitudes of the Greater Khingan Mountains, while the degree of niche migration will gradually increase. Under the 2090s-SSP585 climate scenario, the most suitable area for L. gmelinii will completely disappear, and the climate model niche will be completely separated. Therefore, the protected area of L. gmelinii was demarcated with a target of the productivity characteristics, understory plant diversity characteristics and climate change sensitive area, and the current key protected area was 8.38 × 104 km2. Overall, the study's findings will lay a foundation for the protection and rational development and utilization of cold temperate coniferous forests dominated by L. gmelinii in the northern forested region of the Greater Khingan Mountains.

Soil microbial diversity under different types of interference in birch secondary forest in the Greater Khingan Mountains in China.

Introduction: Soil microorganisms are an important component of soil ecosystems with an indispensable role in forest ecosystems. We analyzed the soil microbial diversity in birch secondary forest formed by natural restoration or artificial reconstruction after interference by burning, clear cutting, and gradient cutting, and the Betula platyphylla Suk undisturbed forest in the Greater Khingan Mountains in China. Methods: Illumina high-throughput sequencing technology was used to analyze the characteristics of the soil microbial community during the restoration process of birch secondary forest caused by the different types of interference. The relationships between bacteria and fungi were analyzed. The gene functions of the soil bacterial community and the ecological functions of soil fungi were predicted using PICRUSt and FunGuild, respectively. Results: At the phylum level, the species and quantity of bacteria were more abundant than that of fungi. At the genus level, no obvious differences in the abundance of bacteria were observed; there were obvious differences in the abundance of fungi. Among the eight sample plots, the artificial larch forest belt had the highest bacterial and fungal alpha diversity, which was slightly higher than undisturbed forest, while the other sample plots were significantly lower. Gradual cutting pure birch forest bacteria and fungi had the highest beta diversity, and artificial larch forest belt bacteria and heavy burn sample plot fungi had the lowest beta diversity. Samples from the cutting and burning sample plots were significantly different from the undisturbed forest at the phylum level of Acidobacteriae, Acidimicrobiia, Mortierellomycetes and Sordariomycetes. We found statistical differences in biomarkers between bacterial and fungal communities in undisturbed forest and artificial larch forest belt and burn sample plots. PICRUSt prediction and FunGuild prediction showed that soil bacterial and fungal communities were rich in gene and ecological functions, respectively. In the microbial network, the stability or anti-interference performance of the fungal community was higher than that of bacteria. Conclusion: Our data reveal the characteristics of the soil microbial community during the restoration process of Betula platyphylla Suk secondary forest under different types of disturbance, which is of great significance for understanding the role of soil microorganisms in the forest ecological cycle.

Influence of salinity on the heterogeneous catalytic ozonation process: Implications to treatment of high salinity wastewater.

The heterogeneous catalytic ozonation process is a promising treatment option for high salinity reverse osmosis concentrate (ROC) however the influence of salts on the catalyst performance is not well understood. In this work, we investigate the effect of salts on the performance of the catalytic ozonation process for treatment of synthetic ROC using a commercially available Fe-loaded Al2O3 catalyst. Our results show that the presence of salts influences the rate and extent of degradation of organic compounds present in the synthetic ROC when subjected to the heterogeneous catalytic ozonation process. Scavenging of aqueous O3 by chloride ions and/or transformation of organics (particularly humics) to more hydrophobic form as a result of charge shielding between adjacent functional groups and/or intramolecular binding by cations inhibits the bulk oxidation of organics to a measurable extent. While the scavenging of aqueous hydroxyl radicals at the salt concentrations investigated here was minimal, the accumulation of chloride ions in the electric double layer near the catalyst surface, particularly when pH< pHpzc, results in more significant scavenging of surface associated hydroxyl radicals. Overall, the presence of salts (particularly chloride ions) has a significant influence on the performance of both conventional and catalytic ozonation processes with some scope to mitigate this effect through appropriate choice of catalyst.

Diagnosis and Treatment Rules of Chronic Kidney Disease and Nursing Intervention Models of Related Mental Diseases Using Electronic Medical Records and Data Mining.

Objective: On the basis of electronic medical records, the data mining technology was adopted to explore the law of chronic kidney disease (CKD) and the intervention mode of mental health of patients. Methods: Based on the electronic medical records, the corresponding data extraction, database establishment, and data cleaning of CKD were performed. After that, the related data analysis, frequency analysis, cluster analysis, and nonparametric analysis were used to explore the laws of CKD diagnosis and treatment and nursing intervention mode of mental illness. The most common causes of CKD were chronic glomerulonephritis (43.76%), aristolochic acid nephritis (16.34%), diabetic nephritis (12.87%), and hypertensive nephritis (11.58%). The major treatment method for end-stage patients was alternative therapies, accounting for 46%. Compared with the depression score before intervention, that of the patients after the mindfulness therapy (50.99 ± 9.77 vs. 47.01 ± 9.33, P=0.024 < 0.5) and target behaviour nursing intervention (52.21 ± 8.12 vs. 48.01 ± 9.33, P=0.032 < 0.05) was obviously decreased. Conclusion: The data mining technology based on electronic records showed a good application prospect in the analysis of the diagnosis and treatment of CKD; and target behaviour nursing and mindfulness intervention were effective psychological intervention models.

High glucose and bupivacaine­induced cytotoxicity is mediated by enhanced apoptosis and impaired autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

Bupivacaine has previously been reported to induce neurotoxicity, which is further enhanced by high glucose levels. In the present study, the underlying molecular mechanisms via which bupivacaine induces cytotoxicity under high glucose conditions were investigated in cultured human SH­SY5Y cells. In order to identify the optimal concentrations of glucose and bupivacaine that induced cytotoxicity, SH­SY5Y cells were treated with 30­100 mM glucose and 0.5­1.0 mM bupivacaine. Based on the dose response experiments, 50 mM glucose and 0.5 mM bupivacaine was used in the present study. The effects that 3­MA (autophagy inhibitor) and rapamycin (RAPA; autophagy inducer) exerted on cell apoptosis, autophagy and the expression of protein kinase R­like endoplasmic reticulum kinase (PERK)­activating transcription factor 4 (ATF4)­C/EBP­homologous protein (CHOP) and inositol­requiring enzyme 1 (IRE1)­tumor necrosis factor receptor associated factor 2 (TRAF2) signaling proteins were measured in high glucose and bupivacaine­treated cells. Cell viability was measured using a Cell Counting Kit­8 assay, cell apoptosis was assessed using flow cytometry, and protein expression was determined using western blot analyses. Compared with the control group, high glucose and bupivacaine significantly increased ATF4, CHOP and caspase­12 expression, increased apoptosis, and decreased p­IRE1, TRAF2, LC3­II/LC3­I and Beclin1 expression. Promoting autophagy with RAPA partly reversed the high glucose and bupivacaine­induced changes in p­PERK, CHOP, TRAF2, Beclin1, caspase­12 and apoptosis, while inhibiting autophagy with 3­MA further enhanced the changes in ATF4, CHOP, p­IRE1, TRAF2 and apoptosis. High glucose and bupivacaine induced cytotoxicity in SH­SY5Y cells, at least in part, through enhancing cell apoptosis and inhibiting autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8-week, prospective, open-label, multicenter, single-arm study.

INTRODUCTION: This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. METHODS: A multicenter, single-arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. RESULTS: A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. DISCUSSION: Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia.

Mammalian target of rapamycin/p70 ribosomal S6 protein kinase signaling is altered by sevoflurane and/or surgery in aged rats.

The mammalian target of rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6k) pathway exerts anti­apoptotic effects that may contribute to disease pathogenesis. The memory impairment in patients with Alzheimer's disease (AD) has been suggested to be contributed to by abnormal mTOR signaling. The aim of the current study was to investigate the association between sevoflurane and/or surgery and AD through the mTOR/p70S6K signaling pathway. Sprague­Dawley rats were randomly assigned to the sevoflurane, surgery or control groups. The animals in the surgery group received a partial hepatectomy under sevoflurane anesthesia. The hippocampal levels of phosphorylated (p)­mTOR, p­p70S6K, caspase­3 and p­tau/total (t)­tau were analyzed. The Morris water maze (MWM) was used to evaluate cognitive function following treatment. The levels of p­mTOR and p­p70S6K were reduced, whereas caspase­3 levels were increased in the surgery group compared with the sevoflurane group. The p­tau/t­tau levels were increased, however, tau mRNA was unaffected by sevoflurane and/or surgery. The rats in the surgery group required a significantly longer time to locate the platform in the MWM test compared with the control and sevoflurane groups. Sevoflurane treatment and/or surgery reduced anti­apoptotic activity, and the postoperative cognitive dysfunction following surgery may be due to mTOR signaling pathway inhibition in aged rats. Increased neuronal apoptosis and tau phosphorylation are suggested to be involved in the association between anesthesia and AD occurrence.

Inhaled sevoflurane may promote progression of amnestic mild cognitive impairment: a prospective, randomized parallel-group study.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is thought to be a transitional stage between normal aging and the development of Alzheimer's disease (AD). Recent studies have suggested that the inhalational anesthetic isoflurane can induce caspase activation and apoptosis, increase aggregates of ß-amyloid (Aß) levels, and enhance Aß aggregation. The aim of this study was to investigate whether previous exposure to different anesthetics induced progression of aMCI. METHODS: A prospective, randomized parallel-group study was completed with 180 patients with aMCI who were randomly assigned to a sevoflurane, propofol or lidocaine epidural anesthesia group (n = 60 per group) during an L3 to L4 or an L4 to L5 spinal surgery. Sixty additional outpatients with aMCI served as a control group. Before surgery, all subjects underwent a neuropsychological assessment. Cerebrospinal fluid (CSF) was obtained by lumbar puncture, and neuropsychological assessments were completed in the clinic. CSF Aß42, total tau and phosphorylated tau181 were quantitatively assayed. The neuropsychological assessments were repeated after 2 years. RESULTS: Two years after anesthesia, the number of AD cases that emerged did not differ significantly between the groups. However, the number of cases of progressive MCI was greater in the sevoflurane group than in the control group. Age correlated linearly with aMCI progression, whereas sex did not. Both patients with AD and progressive MCI had decreased CSF Aß42, increased total tau and increased phosphorylated tau levels compared with those with stable MCI and the controls. CONCLUSIONS: Inhaled sevoflurane accelerated the progression of aMCI to progressive MCI in this selected Chinese population.