Predictive value of the hemoglobin-albumin-lymphocyte-platelet (HALP) index for ICU mortality in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).

The combined index of hemoglobin, albumin, lymphocyte, and platelet (HALP) is a novel indicator reflecting systemic inflammation and nutritional status. To explore the relationship between HALP score and ICU mortality risk in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A total of 1533 AECOPD patients from the eICU Collaborative Research Database (eICU-CRD) between 2014 and 2015 were included in this retrospective cohort study. Univariate and multivariate Cox proportional hazards models were utilized to investigate the association of HALP score, platelet-to-lymphocyte ratio (PLR) score, and lymphocyte-to-monocyte ratio (LMR) score with the ICU mortality risk in patients with AECOPD. Stratified analyses were performed based on patients' ICU admission type, body mass index (BMI), and Acute Physiology, Age and Chronic Health Evaluation IV (APACHE IV) score. Of these 1533 AECOPD patients, 123 (8.00%) patients died in the ICU. Low HALP score [hazard ratio (HR) = 1.69; 95% confidence interval (CI) 1.14-2.53] and low LMR score (HR = 1.60; 95% CI 1.07-2.39) were associated with an increased ICU mortality risk in patients with AECOPD after adjusting for all confounders. Stratified analyses indicated that low HALP score were still associated with a higher ICU mortality risk in patients admitted to ICU by emergency (HR = 1.81; 95% CI 1.11-2.96), obese patients (HR = 2.81; 95% CI 1.29-6.10), and patients with low APACHE scores (HR = 2.87; 95% CI 1.75-4.69). Low HALP score was associated with an increased risk of ICU mortality in patients with AECOPD, suggesting that the HALP score may be a novel prognostic predictor in patients with AECOPD.

[Lung sounds can be used as an indicator for assessing severity of chronic obstructive pulmonary disease at the initial diagnosis].

OBJECTIVE: To assess the value of pulmonary auscultation for evaluating the severity of chronic obstructive pulmonary disease (COPD) at the initial diagnosis. METHODS: The patients with newly diagnosed COPD in our hospital between May, 2016 and May, 2019 were enrolled in this study. According to the findings of pulmonary auscultation, the lung sounds were classified into 5 groups: normal breathing sounds, weakened breathing sounds, weakened breathing sounds with wheezing, obviously weakened breathing sounds, and obviously weakened breathing sounds with wheezing. The pulmonary function of the patients was graded according to GOLD guidelines, and the differential diagnosis of COPD from asthmatic asthma COPD overlap (ACO) was made based on the GOLD guidelines and the European Respiratory Criteria. RESULTS: A total of 1046 newly diagnosed COPD patients were enrolled, including 949 male and 97 female patients with a mean age of 62.6± 8.71. According to the GOLD criteria, 88.1% of the patients were identified to have moderate or above COPD, 50.0% to have severe or above COPD; a further diagnosis of ACO was made in 347 (33.2%) of the patients. ANOVA analysis showed significant differences in disease course, FEV1, FEV1%, FEV1/FVC, FVC, FVC% and mMRC among the 5 auscultation groups (P < 0.001), but FENO did not differ significantly among them (P=0.097). The percentage of patients with wheezing in auscultation was significantly greater in ACO group than in COPD group (P < 0.001). Spearman correlation analysis showed that lung sounds was significantly correlated with disease severity, FEV1, FEV1%, FVC and FVC% of the patients (P < 0.001); Multiple linear regression analysis showed that a longer disease course, a history of smoking and lung sounds were all associated with poorer lung functions and a greater disease severity. CONCLUSIONS: Lung sounds can be used as an indicator for assessing the severity of COPD at the initial diagnosis.

Anxiolytic-like effects of 4-O-methylhonokiol isolated from Magnolia officinalis through enhancement of GABAergic transmission and chloride influx.

Abstract This study investigated the anxiolytic-like effects of 4-O-methylhonokiol, a neolignan compound of Magnolia officinalis, by using the experimental paradigms of anxiety and compared the results with those of a known anxiolytic, diazepam. A single treatment with 4-O-methylhonokiol (0.1, 0.2, and 0.5 mg/kg, p.o.) or treatment for 7 days (0.5 mg/kg in drinking water) increased the percentage of time spent in the open arms and the number of open arms entries in the elevated plus-maze test. However, the 4-O-methylhonokiol-increased percentage of time spent in the open arm was abolished by treatment with flumazenil, a benzodiazepine receptor antagonist (10 mg/kg). 4-O-Methylhonokiol also increased the number of head dips in the hole-board test, but decreased locomotor activity. Molecular experiments revealed that the α1-subunit of γ-aminobutyric acid (GABA) type A receptors was overexpressed in the cortex of brains of mice after treatment with 4-O-methylhonokiol for 7 days. In addition, 4-O-methylhonokiol also increased chloride influx in cultured cortical cells. It is concluded that 4-O-methylhonokiol may have anxiolytic-like effects and that these effects may be mediated by GABAergic transmission with the increase of Cl(-) channel opening.

Anxiolytic-like effects of sanjoinine A isolated from Zizyphi Spinosi Semen: possible involvement of GABAergic transmission.

This experiment was performed to investigate the anxiolytic-like effects of sanjoinine A, one of the major alkaloid compounds in Zizyphi Spinosi Semen (ZSS), by using experimental paradigms of anxiety in comparison with a known anxiolytic, diazepam. Sanjoinine A (2.0 mg/kg) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of time spent in the center zone and the center zone locomotor distance in the open field box experiment. However, sanjoinine A (0.5, 1.0, 2.0 mg/kg) had no effect on locomotor activity, while diazepam (2.0 mg/kg) significantly reduced locomotor activity. Sanjoinine A (0.5, 1.0, 2.0 mg/kg) did not influence the grip force in the grip strength meter test either. Molecular experiments showed that sanjoinine A (2.0, 5.0 microM) increased chloride influx in cultured cerebellar granule cells. In addition, sanjoinine A (5.0 microM) treatment resulted in over-expression of alpha- and gamma-subunits of GABA(A) receptors and glutamic acid decarboxylase (GAD65/67) in cultured cerebellar granule cells. It is concluded that sanjoinine A may have anxiolytic-like effects in the elevated plus-maze, hole-board test and open field test, and these effects may be mediated by GABAergic transmission.

Cyclopeptide alkaloid fraction from Zizyphi Spinosi Semen enhances pentobarbital-induced sleeping behaviors.

This study aimed to investigate effects of cyclopeptide alkaloid fraction of ZSS (CAFZ) on pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by gamma-aminobutyric acid (GABA) receptors Cl(-) channel activation, using a Western blot technique and Cl(-) sensitive fluorescence probe. GABA receptors subunits expression and Cl(-) influx were investigated in cultured cerebellar granule cells. CAFZ shortened sleeping onset and prolonged sleeping time induced by pentobarbital (42 mg/kg). It also significantly increased the falling asleep rate and duration of sleeping time at a sub-hypnotic dosage of pentobarbital (28 mg/kg). In addition, CAFZ in combination with GABA A receptors agonist, muscimol, synergistically prolonged pentobarbital-induced sleeping time. Both of CAFZ and pentobarbital treatment decreased GABA A receptors alpha-subunit expression, but did not change beta- and gamma-subunit expression. However, we found CAFZ and pentobarbital increased Cl(-) influx, CAFZ showed similar effects with muscimol in potentiating Cl(-) influx inducing effects of low-dose pentobarbital. In conclusion, it is suggested that the enhancement of Cl(-) influx by CAFZ may play an important role in the potentiation of pentobarbital-induced sleeping behaviors.

Sanjoinine A isolated from Zizyphi Spinosi Semen augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems.

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of insomnia in oriental countries. This experiment was performed to investigate whether sanjoinine A, one of major alkaloid compounds of ZSS, has hypnotic effects and/or enhances pentobarbital-induced sleeping behaviors through the gamma-aminobutyric acid (GABA)-ergic systems. Sanjoinine A itself did not induce sleeping at the higher dose used in this experiment. However, sanjoinine A prolonged sleeping time and reduced the sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a GABA(A) receptor agonist. Sanjoinine A also increased sleeping rate and sleeping time when administered combined with pentobarbital at a sub-hypnotic dosage and showed synergistic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. In addition, both sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A also showed similar effects with muscimol in potentiating chloride influx inducing effects of low dose pentobarbital. Sanjoinine A decreased GABA(A) receptor alpha-subunit expression and increased gamma-subunit expression, and had no effects on the abundance of beta-subunits in primary cultured cerebellar granule cells, showing different subunit expression from pentobarbital. In addition, we found that sanjoinine A also enhanced expression of glutamic acid decarboxylase (GAD), but pentobarbital did not. In conclusion, sanjoinine A itself does not induce sleeping, but it augments pentobarbital-induced sleeping behaviors through the modification of GABA-ergic systems.