Mechanism and treatments of antipsychotic-induced weight gain.

The long-term use of antipsychotics (APs) may cause a variety of diseases, such as metabolic syndrome, antipsychotic-induced weight gain (AIWG), and even obesity. This paper reviews the various mechanisms of AIWG and obesity in detail, involving genetics, the central nervous system, the neuroendocrine system, and the gut microbiome. The common drug and non-drug therapies used in clinical practice are also introduced, providing the basis for research on the molecular mechanisms and the future selection of treatments.

Application of the respiratory "critical care-sub-critical care-rehabilitation integrated management model" in severe stroke associated pneumonia.

BACKGROUND: This study aimed to explore the feasibility of applying the respiratory "critical care-sub-critical care-rehabilitation integrated management model" in severe stroke-associated pneumonia and evaluate its effect. METHODS: From January to September 2018, 24 patients with severe stroke-associated pneumonia, who were admitted to the Respiratory Intensive Care Unit of the Respiratory and Critical Care Medicine Department of Henan Provincial People's Hospital, were randomly divided into two groups: integrated management group and control group. According to the admission criteria of the respiratory "critical care-sub-critical care-rehabilitation integrated model" prescribed by the above-mentioned hospital, patients were grouped. The professional respiratory therapy team participated in the whole treatment. The acute physiology and chronic health evaluation II (APACHE II) score, clinical pulmonary infection score (CPIS) and oxygenation index of these two groups were dynamically observed, and the average hospital stay, 28-day mortality and patient satisfaction were investigated. RESULTS: Patients in the integrated management group and control group were similar before treatment (P > 0.05). After treatment, the main indicators, the APACHE II score, CPIS score and oxygenation index, were significantly different between the integration group and control group (P < 0.05). The secondary indicators, the average hospitalization days and patient/family member satisfaction scores, were also significantly different between the integration group and control group (P < 0.05). However, the 28-day mortality wasn't significantly different (P > 0.05). CONCLUSIONS: For patients with severe stroke-associated pneumonia, it was feasible to implement the respiratory "critical care-sub-critical care-rehabilitation integrated management model", which could significantly improve the treatment effect, shorten average hospitalization days and improve patient/family satisfaction.

iTRAQ-based quantitative proteomic analysis provides insight for molecular mechanism of neuroticism.

BACKGROUND: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism. METHODS: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology. RESULTS: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway. CONCLUSIONS: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population.

Angiotensin II Receptor Type 1 Antagonists Modulate Vascular Smooth Muscle Cell Proliferation and Migration via AMPK/mTOR.

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) in the vascular wall are crucial pathological events involved in cardiovascular impairments including hypertension, heart failure, and atherosclerosis. At the molecular level, the mammalian target of rapamycin (mTOR)-ribosomal protein S6 kinase beta-1 (p70S6K) signaling pathway is essential to potentiate VSMC proliferation and migration. Although angiotensin II receptor type 1 -(AT1-R) antagonists such as valsartan and telmisartan have a significant cardiovascular protective effect, the molecular basis of this class of drugs in VSMC proliferation and migration remains elusive. By using cultured VSMCs, adenosine monophosphate-activated protein kinase (AMPK) α2 knockout mice, and hypertensive rat models, this study investigated whether AT1-R antagonists can inhibit the mTOR-p70S6K signaling pathway in VSMCs and the vascular wall. Valsartan activated AMPK, which in turn suppressed reactive oxygen species production and consequently attenuated VSMC proliferation and migration. In vivo, a clinical dose of telmisartan significantly inhibited the mTOR-p70S6K signaling pathway in the vascular wall of wild-type but not AMPKα2-/- mice. Furthermore, spontaneously hypertensive rats had significantly elevated phosphorylation of mTOR and p70S6K in the aorta compared to Wistar-Kyoto rats, which were reduced by telmisartan administration. These data suggest that AT1-R antagonists inhibit VSMC proliferation and migration via their regulation of AMPK, mTOR, and p70S6K, which contribute to the cardioprotective effects of these drugs.

Inhibition of AMPK expression in skeletal muscle by systemic inflammation in COPD rats.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow limitation and inflammation. Meanwhile, COPD also is associated with metabolic disorders, such as skeletal muscle weakness. Strikingly, activation of AMP-activated protein kinase (AMPK) exerts critical roles in energy metabolism. However, it remains unclear whether and how the expression levels of AMPK are affected in the COPD model rats which may lead to the dysfunction of the skeletal muscle in these rats. METHODS: Here we developed a rat model of COPD, and we investigated the morphological changes of peripheral skeletal muscle and measured the levels of tumor necrosis factor -α (TNF-α) and AMPK in skeletal muscle by using approaches that include immunohistochemistry and polymerase chain reaction (PCR). RESULTS: We found that the expression levels of both AMPK mRNA and protein in skeletal muscles were significantly reduced in the COPD model rats, in comparison to those from the control rats, the COPD model rats that received treatments with AICAR and resveratrol, whereas the expression levels of TNF-α were elevated in COPD rats. CONCLUSION: Such findings indicate that AMPK may serve as a target for therapeutic intervention in the treatment of muscle weakness in COPD patients.

[Impact of extracorporeal carbon dioxide removal combined with continuous renal replacement therapy on diaphragmatic function in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the effects of extracorporeal carbon dioxide removal (ECCO2R) combined with continuous renal replacement therapy (CRRT) on respiratory efficiency and diaphragm function in patients with acute respiratory distress syndrome (ARDS) received mechanical ventilation. METHODS: A prospective randomized controlled study was conducted. Sixty patients with mild to moderate ARDS admitted to the department of respiratory and critical care medicine of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled, and they were divided into observation group and control group according to the random number table method, with 30 cases in each group. All patients received antibiotics, anti-inflammatory, and mechanical ventilation therapy. On this basis, the observation group received ECCO2R and CRRT, while the control group received bedside CRRT. Baseline data including gender, age, etiology, acute physiology and chronic health evaluation II (APACHE II), etc., were recorded. Arterial blood gas analysis [including arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and oxygenation index (PaO2/FiO2)] was performed at 12 hours and 24 hours during the treatment, and respiratory mechanics parameters [including tidal volume, respiratory rate, maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP)] were recorded, and rapid shallow breathing index (RSBI) was calculated. The levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Diaphragm thickness and diaphragm activity were measured by ultrasonography at 24 hours during the treatment. RESULTS: There were no significantly differences in age, gender, etiology, and APACHE II score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the 12 hours after treatment, the PaO2 and PaO2/FiO2 in the observation group significantly increased, PaCO2 significantly decreased, RSBI significantly decreased, MEP and MIP significantly increased, and serum GSH-Px and MDA significantly decreased, while SOD significantly increased at 24 hours during the treatment. In the control group, only PaCO2 significantly decreased. Compared with the control group, the PaCO2 significantly decreased in the observation group at 12 hours and 24 hours [mmHg (1 mmHg≈0.133 kPa): 55.05±7.57 vs. 59.49±6.95, 52.77±7.88 vs. 58.25±6.92, both P < 0.05], but no significantly differences in PaO2 and PaO2/FiO2. Compared with the control group, the observation group showed significant decreases in RSBI at 12 hours and 24 hours (times×min-1×L-1: 85.92±8.83 vs. 90.38±3.78, 75.73±3.86 vs. 90.05±3.66, both P < 0.05), significant increases in MEP and MIP [MEP (mmH2O, 1 mmH2O≈0.01 kPa): 86.64±5.99 vs. 83.88±4.18, 93.70±5.59 vs. 85.04±3.73; MIP (mmH2O): 44.19±6.66 vs. 41.17±3.13, 57.52±5.28 vs. 42.34±5.39, all P < 0.05], and significant decreases in serum GSH-Px and MDA [GSH-Px (mg/L): 78.52±8.72 vs. 82.10±3.37, 57.11±4.67 vs. 81.17±5.13; MDA (µmol/L): 7.84±1.97 vs. 8.71±0.83, 3.67±0.78 vs. 8.41±1.09, all P < 0.05], as well as a significant increase in SOD (U/L: 681.85±49.24 vs. 659.40±26.47, 782.32±40.56 vs. 676.65±51.97, both P < 0.05). Compared with the control group, the observation group showed significant increases in diaphragm thickness and diaphragm activity at 24 hours of treatment [diaphragm thickness (cm): 1.93±0.28 vs. 1.40±0.24, diaphragmatic thickening fraction: (0.22±0.04)% vs. (0.19±0.02)%, quiet breathing diaphragm displacement (cm): 1.42±0.13 vs. 1.36±0.06, deep breathing diaphragm displacement (cm): 5.11±0.75 vs. 2.64±0.59, all P < 0.05]. CONCLUSIONS: ECCO2R combined with CRRT can reduce work of breathing and oxidative stress levels in ARDS patients receiving non-invasive ventilation, and protect diaphragm function.

Exploring the mechanism of Suanzaoren decoction in treatment of insomnia based on network pharmacology and molecular docking.

Objective: To explore the functional mechanisms of Suanzaoren decoction (SZRD) for treating insomnia using network pharmacology and molecular docking. Methods: The active ingredients and corresponding targets of SZRD were obtained from the Traditional Chinese Medicine Systems Pharmacology database, and then, the names of the target proteins were standardized using the UniProt database. The insomnia-related targets were obtained from the GeneCards, DisGeNET, and DrugBank databases. Next, a Venn diagram comprising the drug and disease targets was created, and the intersecting targets were used to draw the active ingredient-target network diagram using Cytoscape software. Next, the STRING database was used to build a protein-protein interaction network, followed by cluster analysis using the MCODE plug-in. The Database for Annotation, Visualization, Integrated Discovery (i.e., DAVID), and the Metascape database were used for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. AutoDock Vina and Pymol software were used for molecular docking. Results: SZRD contained 138 active ingredients, corresponding to 239 targets. We also identified 2,062 insomnia-related targets, among which, 95 drug and disease targets intersected. The GO analysis identified 490, 62, and 114 genes related to biological processes, cellular components, and molecular functions, respectively. Lipid and atherosclerosis, chemical carcinogen-receptor activation, and neuroactive ligand-receptor interaction were the most common pathways in the KEGG analysis. Molecular docking demonstrated that the primary active components of SZRD for insomnia had good binding capabilities with the core proteins in PPI network. Conclusion: Insomnia treatment with SZRD involves multiple targets and signaling pathways, which may improve insomnia by reducing inflammation, regulating neurotransmitters.

Psychological, physiological, and biochemical correlations after negative emotional videos in college students with and without premenstrual syndrome.

Introduction: Women with premenstrual syndrome (PMS) suffer heavily from emotional problems, the pathogenesis of which is believed to be related to the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS) and central nervous system (CNS). We took into account all 3 aspects to observed the psychological, physiological and biochemical correlations under anger and sadness in college students with and without PMS. Methods: 33 students with PMS and 24 healthy students participated in the emotion induction experiment, and were required to fill out self-report scales. Their salivary cortisol (SCort), skin conductivity level (SCL), heart rate variability (HRV), blood pressure (BP) and electroencephalogram (EEG) data were collected at the resting stage and 10-15 minutes after each video. Results: Compared to healthy controls, students with PMS showed lower SCort level and higher VLF at rest, and no statistic difference in activities of ANS and HPA axis after emotional videos, but different results in EEG in all conditions. The decreases in SBP during angry video, SCort after angry and neutral videos, and increases in θ band power during sad video were moderately correlated with increases in PMS score. No intergroup differences were found in self-report emotions. Discussion: Students with PMS had lower activity of HPA axis and possibly higher activity of PNS at rest, and different response patterns in CNS in all conditions. Several EEG frequencies, especially θ band, in specific encephalic regions during emotional videos, as well as declined HPA activities in dealing with angry and neutral stressors, in which γ activity in frontal lobe may play a role, showed moderate correlations with more severe PMS.

[Predictive value of HACOR score on the clinical outcome of non-invasive positive pressure ventilation in the treatment of chronic obstructive pulmonary disease with pulmonary encephalopathy].

OBJECTIVE: To explore the predictive value of HACOR score [heart rate (H), acidosis (A), consciousness (C), oxygenation (O), and respiratory rate (R)] on the clinical outcome of non-invasive positive pressure ventilation in patients with pulmonary encephalopathy due to chronic obstructive pulmonary disease (COPD). METHODS: A prospective study was conducted. The patients with COPD combined with pulmonary encephalopathy who were admitted to Henan Provincial People's Hospital from January 1, 2017 to June 1, 2021 and initially received non-invasive positive pressure ventilation were enrolled. Besides non-invasive positive pressure ventilation, standard medical treatments were delivered to these patients according to guidelines. The need for endotracheal intubation was judged as failure of non-invasive ventilation treatment. Early failure was defined as the need for endotracheal intubation within 48 hours of treatment, and late failure was defined as the need for endotracheal intubation 48 hours and later. The HACOR score at different time points after non-invasive ventilation, the length of intensive care unit (ICU) stay, the total length of hospital stay, and the clinical outcome were recorded. The above indexes of patients with non-invasive ventilation were compared between successful and failed groups. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive effect of HACOR score on the failure of non-invasive positive pressure ventilation in the treatment of COPD with pulmonary encephalopathy. RESULTS: A total of 630 patients were evaluated, and 51 patients were enrolled, including 42 males (82.35%) and 9 females (17.65%), with a median age of 70.0 (62.0, 78.0) years old. Among the 51 patients, 36 patients (70.59%) were successfully treated with non-invasive ventilation and discharged from the hospital eventually, and 15 patients (29.41%) failed and switched to invasive ventilation, of which 10 patients (19.61%) were defined early failure, 5 patients (9.80%) were late failure. The length of ICU and the total length of hospital stay of the non-invasive ventilation successful group were significantly longer than those of the non-invasive ventilation failure group [length of ICU stay (days): 13.0 (10.0, 16.0) vs. 5.0 (3.0, 8.0), total length of hospital stay (days): 23.0 (12.0, 28.0) vs. 12.0 (9.0, 15.0), both P < 0.01]. The HACOR score of patients at 1-2 hours in the non-invasive ventilation failure group was significantly higher than that in the successful group [10.47 (6.00, 16.00) vs. 6.00 (3.25, 8.00), P < 0.05]. However, there was no significant difference in HACOR score before non-invasive ventilation and at 3-6 hours between the two groups. The ROC curve showed that the area under the ROC curve (AUC) of 1-2 hour HACOR score after non-invasive ventilation for predicting non-invasive ventilation failure in COPD patients with pulmonary encephalopathy was 0.686, and the 95% confidence interval (95%CI) was 0.504-0.868. When the best cut-off value was 10.50, the sensitivity was 60.03%, the specificity was 86.10%, positive predictive value was 91.23%, and negative predictive value was 47.21%. CONCLUSIONS: Non-invasive positive pressure ventilation could prevent 70.59% of COPD patients with pulmonary encephalopathy from intubation. HACOR score was valuable to predict non-invasive positive pressure ventilation failure in pulmonary encephalopathy patients due to COPD.

[Establishment of rat model of ischemic stroke with qi deficiency and blood stasis syndrome and its evaluation system].

OBJECTIVE: To probe into the establishing method and the evaluating system for rat model of ischemic stroke with qi deficiency and blood stasis syndrome (QDBS). METHODS: A rat model of ischemic stroke of QDBS was established by continual exhaustive swimming followed with middle cerebral artery occlusion (MCAO), and evaluated by analyzing the changes of exterior signs, tongue figure, hemorrheologic characters and brain histomorphology in the model rats. RESULTS: The model rats showed a state of QDBS in the course of continual exhaustive swimming, such as slower weight gain, postponed food intake, darker tongue and longer sublingual veins; and presented the characteristics of cerebral ischemia with QDBS syndrome after MCAO, they were inactive, weak, and hemiplegic, with dark purple tongue and longer blue sublingual veins. Moreover, hemorrheologic examinations showed blood hyperviscosity and high platelet aggregation rate, and histomorphologic examinations showed a special figure of ischemic changes. CONCLUSION: Continual exhausting swimming followed by MCAO is a method for establishing a rat model of ischemic stroke with QDBS syndrome, and its evaluating system could be constituted by multiple criteria, including exterior signs, tongue figure, hemorrheologic and histomorphologic indexes, etc.

Downregulation of microRNA­30a in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis patients.

MicroRNAs (miRs) are short, highly conserved small noncoding RNA molecules with fundamental roles in regulating gene expression. To identify miR biomarkers associated with idiopathic pulmonary fibrosis (IPF), the expression pattern of miRs in exosomes from bronchoalveolar lavage fluid (BALF) of elderly patients with IPF were evaluated. High­throughput quantitative detection of miR expression using a microarray indicated that miR­125b, miR­128, miR­21, miR­100, miR­140­3p and miR­374b were upregulated in patients with IPF, while let­7d, miR­103, miR­26 and miR­30a­5p were downregulated. The expression level of miR­30a­5p was further examined, and its potential target genes were predicted using target gene prediction analysis software. A direct regulatory association was confirmed between miR­30a­5p and TGF­ß activated kinase 1/MAP3K7 binding protein 3 (TAB3) via a dual­luciferase reporter assay. Overexpression of miR­30a­5p decreased TAB3, α­smooth muscle actin and fibronectin expression in A549 cells with or without transforming growth factor­ß1 treatment. The decreased expression of miR­30a in the BALF of patients with IPF, along with the consequential increase in TAB3 expression, may be a crucial factor in IPF progression.

[Effects of dexmedetomidine hydrochloride on ERK1/2 activation in a rat model of ventilator-induced lung injury].

OBJECTIVE: To investigate the effect of dexmedetomidine hydrochloride on inflammatory lung injury and phosphorylation of extracellular regulated protein (ERK1/2) in a rat model of ventilator-induced lung injury (VILI). METHODS: Thirty-six adult male SD rats were randomized into 3 groups (n=12) to receive a 4-h standard ventilation (group C, with tidal volume of 8 ml/kg and respiratory rate of 90/min), high-tidal volume ventilation (group H, with tidal volume of 20 ml/kg and respiratory rate of 50 /min), and high-tidal volume ventilation plus 0.5 µg·kg(-1)·h(-1) dexmedetomidine infusion (group D), with the maintenance of a positive end expiratory pressure (PEEP) of 0 cmH(2)O. After mechanical ventilation the rats were sacrificed to collect the lung lavage liquid and lung tissue to examine the pulmonary inflammatory changes and tumor necrosis factor-α (TNF-α) expression as well as the expressions of ERK1/2 and p-ERK1/2. RESULTS: Groups H and D showed obvious lung injury and significant elevations of the total protein, WBC, MPO, TNF-α, and ERK1/2 phosphorylation as compared with those of group C. The rats in group D showed milder lung pathologies with significantly lower levels of phosphorylation of ERK1/2 and TNF-α compared with those in group H. CONCLUSION: Dexmedetomidine can significantly attenuate VILI, decrease the production of the inflammatory molecules, and inhibit the activation of ERK1/2, demonstrating a protective effect against VILI.