Differential expression of microRNAs in serum exosomes of obese and non-obese mice and analysis of their function.

OBJECTIVE: To extract exosomes from obese and non-obese mice, screen specifically expressed microRNAs by high-throughput sequencing and explore their roles. METHODS: An animal obesity model was constructed, and the successful construction of the obesity model was verified by HE staining, Western Blot and RT-qPCR. In addition, exosomes were extracted and verified by Western Blot. High-throughput sequencing was performed on the extracted serum exosomes to screen for differentially expressed microRNAs. fluorescence quantitative RT-PCR (RT-qPCR) was used to validate the differentially expressed miRNAs and explore their functions. RESULTS: 8 microRNAs were up-regulated and 11 microRNAs were down-regulated. mmu-miR-674-5p and X_28316 were significantly down-regulated and had the greatest impact on protein pathways. 8_13258 was significantly up-regulated and affected multiple protein pathways. GO enrichment analysis suggested that the differentially expressed microRNAs were mainly involved in the cleavage of microtubule activity, transferase activity/transferase pentameric acid. GO enrichment analysis suggested that differentially expressed microRNAs were mainly involved in the processes of cleavage microtubule activity, transferase activity/transfer pentamer, and threonine phosphatase/threonine kinase activity.KEGG pathway enrichment analysis showed that differentially expressed microRNAs were mainly involved in the processes of regulating the phosphorylation of TP53 activity, the G2/M DNA damage checkpoint, and the processing of the ends of DNA double-strand breaks. Protein interaction networks were enriched for Stat3, Fgr, Camk2b, Rac1, Asb6, and Ankfy1. Suggesting that they may be mediated by differential genes to participate in the process of insulin resistance. qRT-PCR results showed that the expression trend of mmu-miR-674-5p was consistent with the sequencing results. It suggests that it may be able to participate in the regulation of insulin resistance as a target gene. CONCLUSION: microRNAs were differentially expressed in serum exosomes of obese and non-obese mice and might be involved in the specific regulation of insulin resistance. mmu-miR-674-5p was differentially expressed significantly and the validation trend was consistent with it, suggesting that it might be able to participate in the regulation of insulin resistance as a target gene.

Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease (NAFLD) in Non-Obese Patients with Schizophrenia: A Retrospective Study.

Background: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China. Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m2 was considered obese, and BMI < 25 kg/m2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University. Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients. Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia.

Self-assembly nanoplatform of platinum (â £) prodrug for enhanced ovarian cancer therapy.

Cisplatin is a metal platinum complex commonly used in the field of anti-tumor and one of the most commonly used drugs in combination chemotherapy. However, chemotherapy with Cisplatin induced overexpression of cyclooxygenase-2 (COX-2) protein in tumor cells, which could impair the therapeutic effect of chemotherapy on tumor progression. Here, we presented a novel method for the treatment of ovarian cancer with a self-assembly based nano-system. Cisplatin and tolfenamic acid were each linked to linoleic acid to give them the ability to self-assemble into nanoparticles in water. TPNPs had flexible drug ratio adjustability, homogeneous stability, and high drug loading capacity. Compared with Cisplatin, TPNPs could promote cellular uptake and tumor aggregation, co-induce enhanced apoptosis and tumor growth inhibition by inhibiting COX-2 in the mice xenograft model of human ovarian cancer, and reduce systemic toxicity. Therefore, TPNPs is a promising antitumor drug as a kind of self-assembly nano-prodrug with high drug load.

Prevalence and associated factors of obesity and overweight in Chinese patients with bipolar disorder.

Object: Despite abundant literature demonstrating a high prevalence of obesity and overweight in people with bipolar disorder (BD), little is known about this topic in China. Therefore, we assessed the prevalence and associated factors of obesity and overweight among inpatients with BD in our hospital, one of the largest public psychiatric hospitals in China. Methods: In this retrospective, cross-sectional study, 1,169 inpatients ≥18 years with BD during 2019 were included. Obesity was defined as having a BMI ≥25 kg/m2, and overweight was defined as having a BMI from 23 kg/m2 to <25 kg/m2. Binary logistic regression analysis was performed to identify factors associated with obesity and overweight. Results: The prevalence of obesity and overweight was 21.0% and 32.2% in patients with BD, respectively. Compared to patients with overweight and normal weight, patients with obesity were older, had a longer duration of BD and a longer length of hospital stay, had a higher prevalence of diabetes and hypertension, and had a higher level of all metabolic indices, except for HDL cholesterol. Binary logistic regression analysis showed that duration of BD, uric acid, alanine aminotransferase (ALT), triglyceride, and LDL cholesterol were significantly associated with obesity, and male sex and uric acid level were significantly associated with overweight (p < 0.05). Conclusions: Obesity and overweight were fairly prevalent in Chinese BD patients, and several factors were related to obesity and overweight. The results of the present study call for the need to implement early screening, prevention and interventions for obesity and overweight in patients with BD in China.

An injectable metal nanoparticle containing cellulose derivative-based hydrogels: Evaluation of antibacterial and in vitro-vivo wound healing activity in children with burn injuries.

The preparation of hydrogels for wound healing properties with high antibacterial activities and good biosafety concurrently can be relatively challenging. For addressing these issues, we report on the synthesis and characterisation of a nanocomposite hydrogel dressing by introducing the silver nanoparticles in hydroxypropyl methylcellulose-hydroxyapatite scaffold hydrogel (HMC-HA/AgNPs). The different concentrations of AgNPs in HMC-HA/AgNPs hydrogels were confirmed by swelling ratio, degradation, and gelatin time. The synthesised HMC-HA/AgNPs hydrogels were further characterised using the UV-visible, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrum, and X-ray diffraction. The results showed that the novel HMC-HA/AgNPs hydrogel exhibited a porous 3D network and high mechanical properties because of the inter-molecular and intra-molecular interactions. The AgNPs give the HMC-HA hydrogels excellent antibacterial activities against both Staphylococcus aureus and Escherichia coli, without any chemical reductant and cross-linking agent required endows the hydrogel high biocompatibility. More importantly, HMC-HA/AgNPs effectively repaired wound defects in mice models, and wound healing reached 94.5 ± 1.4% within 16 days. The HMC-HA hydrogel with AgNPs showed excellent antimicrobial activity and burn wound healing. Therefore, these HMC-HA/AgNPs hydrogels have great potential as an injectable hydrogel for wound healing activity in children with burn injuries.

Clozapine Use in Patients with Early-Stage Schizophrenia in a Chinese Psychiatric Hospital.

OBJECTIVE: Previous studies suggest that clozapine is commonly underutilized and that its initiation is delayed in patients with first-episode schizophrenia. Knowledge regarding clozapine use among Chinese patients with early-stage schizophrenia is limited. The aim of the present study was to investigate the point prevalence of and patterns and factors associated with clozapine use in patients with early-stage schizophrenia discharged from a psychiatric hospital in China. METHODS: A retrospective study was conducted to analyze the prescriptions of 867 consecutive patients with early-stage schizophrenia who were admitted to the Affiliated Brain Hospital of Guangzhou Medical University between Jan 1, 2011 and Dec 31, 2016. RESULTS: At discharge from the hospital, 114 (13.1%) patients were prescribed clozapine. Among the patients taking clozapine, 93 patients (81.6%) were prescribed clozapine polypharmacy, and only 21 patients (18.4%) were prescribed clozapine monotherapy. None of the patients were prescribed an overdose of clozapine. The mean daily dosage of clozapine was 160.97 mg, 149.05 mg and 213.69 mg among all patients taking clozapine, patients taking clozapine polypharmacy and patients taking clozapine monotherapy, respectively. The antipsychotic most frequently combined with clozapine was risperidone. Logistic regression suggested that the length of hospital stay, high school education, lower benzodiazepine use and antipsychotic polypharmacy were independently and significantly associated with clozapine use (P<0.05). CONCLUSION: Although clozapine has been commonly used in China in recent years, the present study found that clozapine was not commonly used in patients with early-stage schizophrenia. An underutilization and delayed initiation of clozapine may exist in a portion of patients with early-stage schizophrenia. Given the unfavorable outcomes of underutilized and delayed clozapine use, future studies may be needed to assess and increase clozapine use in this population.

Psychotic Symptoms and Attitudes toward Medication Mediate the Effect of Insight on Personal-Social Functions in Patients with Schizophrenia: One-Year Randomized Controlled Trial and Follow-Up.

AIMS: This study aimed to investigate the mediating pathway of 3 factors (psychotic symptoms, attitude toward medication, and cognitive processing speed) on the effect of insight on personal-social functioning in patients with schizophrenia. METHODS: Chinese inpatients with schizophrenia (n = 168; mean age 18 ± 50 years) diagnosed according to the DSM-IV were randomly assigned to treatment with antipsychotic medication alone or combined treatment. Positive and Negative Syndrome Scale (PANSS), Drug Attitude Inventory (DAI), Assessment of Insight (SAI), and Social-Personal Performance Scale (PSPS) scores were evaluated at baseline and at 3, 6, and 12 months. Cognitive function was assessed at baseline. Multiple mediation analyses were conducted with baseline data, end point data, and changes-in-scale scores between baseline and the end point, respectively. RESULTS: At baseline and at 12 months, only psychotic symptoms mediated the effect of insight on personal-social functioning. For changes-in-scale scores over the 12-month follow-up, in patients receiving treatment with medication alone, the effect of improved insight on improved personal-social function was mediated by psychotic symptoms only; in patients receiving a combined treatment, the effect of improved insight on improved personal-social functioning was mediated by both psychotic symptoms and attitudes toward medication, independently. CONCLUSIONS: The link between insight and personal-social functions is mainly mediated by psychotic symptoms. Psychosocial intervention improves the predicting effect of insight on personal-social function by improving both the attitude toward medication and psychotic symptoms independently.

Two-stage integrated care versus antipsychotic medication alone on outcomes of schizophrenia: One-year randomized controlled trial and follow-up.

Integrated care can reduce rate of relapse and improve personal and social functions in patients with schizophrenia. We established and evaluated a new model of "intensive-consolidation" two-stage integrated care (IC) for inpatients with schizophrenia. Data were collected between 2012 and 2015. Chinese inpatients with schizophrenia (n=170) diagnosed according to DSM-IV were randomly assigned to antipsychotic medication-alone (n=84) or two-stage IC (n=86) and followed up for 12 months. The IC model included intensive treatments (antipsychotics plus the cognitive behavior therapy and rehabilitation treatment) during hospitalization and 3-time consolidation treatments with 3-month intervals at clinics. Outcome measures included the rate of relapse, psychiatric symptoms and social functioning. Compared with medication-alone group, the rate of relapse were significantly lower in IC group (p=0.012); the Mixed-Effects Model for Repeated-Measures analyses showed that the IC group significantly improved in positive symptoms over time; greater improvement in self-care and less aggressive behaviors were observed over time in IC group (all p<0.008). The findings support the feasibility and effectiveness of the new two-stage model of integrated care as an intervention for middle-acute-phase inpatients with schizophrenia. The model is particularly informative to countries where medical resources are mainly distributed in developed regions.

Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. METHODS: Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. RESULTS: A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). CONCLUSION: Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

Triphenyltin degradation and proteomic response by an engineered Escherichia coli expressing cytochrome P450 enzyme.

Although triphenyltin (TPT) degradation pathway has been determined, information about the enzyme and protein networks involved was severely limited. To this end, a cytochrome P450 hydroxylase (CYP450) gene from Bacillus thuringiensis was cloned and expressed in Escherichia coli BL21 (DE3), namely E. coli pET32a-CYP450, whose dosage at 1gL-1 could degrade 54.6% TPT at 1mgL-1 within 6 d through attacking the carbon-tin bonds of TPT by CYP450. Sequence analysis verified that the CYP450 gene had a 1214bp open reading frame, encoding a protein with 404 amino acids. Proteomic analysis determined that 60 proteins were significantly differentially regulated expression in E. coli pET32a-CYP450 after TPT degradation. The up-regulated proteins enriched in a network related to transport, cell division, biosynthesis of amino acids and secondary metabolites, and microbial metabolism in diverse environments. The current findings demonstrated for the first time that P450 received electrons transferring from NADH could effectively cleave carbon-metal bonds.

Interactions among triphenyltin degradation, phospholipid synthesis and membrane characteristics of Bacillus thuringiensis in the presence of d-malic acid.

Degradation pathway and surface biosorption of triphenyltin (TPT) by effective microbes have been investigated in the past. However, unclear interactions among membrane components and TPT binding and transport are still obstacles to understanding TPT biotransformation. To reveal the mechanism involved, the phospholipid expression, membrane potential, cellular mechanism and molecular dynamics between TPT and fatty acids (FAs) during the TPT degradation process in the presence of d-malic acid (DMA) were studied. The results show that the degradation efficiency of 1 mg L-1 TPT by Bacillus thuringiensis (1 g L-1) with 0.5 or 1 mg L-1 DMA reached values up to approximately 90% due to the promotion of element metabolism and cellular activity, and the depression of FA synthesis induced by DMA. The addition of DMA caused conversion of more linoleic acid into 10-oxo-12(Z)-octadecenoic acid, increased the membrane permeability, and alleviated the decrease in membrane potential, resulting in TPT transport and degradation. Fluorescence analysis reveals that the endospore of B. thuringiensis could act as an indicator for membrane potential and cellular activities. The current findings are advantageous for acceleration of biosorption, transport and removal of pollutants from natural environments.

Long- and short-term inpatients with schizophrenia in China: implications for community-based service development.

INTRODUCTION: There is an increasing interest in the patterns of mental health care of people with serious mental illnesses in China, where outpatient and community-based care are not fully developed and long-term hospitalization is still not uncommon. Comparison of sociodemographic and clinical characteristics of long-term and short-term inpatients diagnosed with schizophrenia can be informative about pattern of treatment and their relationship to services needs. METHODS: Seventy-three long-term schizophrenia inpatients (current length of stay of more than 5 years) were compared to 116 short-term schizophrenia inpatients (current length of stay of 30 days or less) assessed with the Individual Background Questionnaire, the Positive and Negative Syndrome Scale (PANSS) and the Social Support Rating Scale (SSRS). RESULTS: There was no significant difference between the groups on the total PANSS symptom score but the short-term inpatients scored significantly higher than their long-term counterparts on the Positive Syndrome sub-scale and the SSRS and lower on the Negative Syndrome sub-scale. DISCUSSION: Differences in symptomatology and social functioning may be related to better medication adherence and more extended social isolation among long-term inpatients while the increased positive symptoms are likely to reflect more acute disease process in short-term inpatients, and possibly poorer medication adherence. These differences may be especially pronounced in developing countries like China in which community-based services need to be more fully developed to facilitate medication adherence and prevent relapse, and to support community adjustment of socially isolated patients who otherwise require hospitalization.

Comparison of psychosocial determinants in inpatients with first-episode and chronic schizophrenia in china.

This study aimed at comparing psychosocial factors in inpatients with first-episode and chronic schizophrenia in China. A sample of 197 first-episode schizophrenia inpatients was compared with 392 chronic schizophrenics using Positive and Negative Syndrome Scale, Social Support Rating Scale and Childhood Traumatic Questionnaire. Our findings showed that chronic schizophrenic patients had significant higher negative symptoms but lower on positive symptoms. They were also less likely to receive social support. Our results provide understanding on the existing differences between first-episode and chronic schizophrenia. Therefore, comprehensive nursing interventions are needed to facilitate social support and medication adherence in order to prevent relapses.