Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To study the pharmacokinetics of the broad-spectrum antifungal drug butenafine nanomicelles (BTF-NM) after topical instillation.Methods:The self-assembly method was used to prepare BTF-NM.The particle size, Zeta potential, and polydispersity index (PDI) of BTF-NM were measured by a nano-particle size-Zeta potential analyzer, and the encapsulation efficiency was determined by high-performance liquid chromatography (HPLC). Forty-two healthy New Zealand white rabbits without eye disease were randomly divided into the BTF-NM group and the BTF suspension (BTF-S) group.The corresponding drugs were instilled in the conjunctival sac with a single instillation of 50 μl.The 7.5 mm filter paper was placed in the conjunctival sac of rabbit eye for 1 minute at 5, 15, 30, 60, 120, 180, 240 minutes after the administration.Then the rabbits were sacrificed by intravenous injection of 4% sodium pentobarbital solution through the ears of the rabbits.The aqueous humor was extracted and the corneal tissue was dissected.The drug concentration of BTF in different tissues was measured by HPLC.The study was approved by the Life Science Ethics Review Committee of Henan Eye Hospital (No.HNEECA-2019-01).Results:The particle size and PDI of BTF-NM were (15.65±0.04)nm and 0.11±0.01, respectively, the Zeta potential was (-0.29±0.36)mV, the encapsulation rate was (98.38±0.29)%.The peak time of the drug both in tears and corneal tissues after BTF-NM application was 5 minutes.The peak concentrations of the drug in tears and corneas of the BTF-NM group were (485.21±66.29) μg/g and (12.53±2.32) μg/g, which were 5.6 and 78 times than that of the BTF-S group, respectively.Within the observation time, the mass fractions of the drug in tears and corneas of the BTF-NM group at each time point were significantly higher than those of BTF-S group at corresponding time points (all at P<0.01), respectively.The area under the concentration-time curve (AUC) 0-240 minutes in tears and corneas of the BTF-NM group was 7 488.90 (μg/g)·minute and 829.01 (μg/g)·minute, which was 7.2 and 52 times than that of the BTF-S group, respectively.No drugs were detected in the aqueous humor of the BTF-NM group and the BTF-S group. Conclusions:BTF-NM is an ideal agent with a simple preparing process, high drug encapsulation efficiency and small particle size.Compared with BTF suspension, BTF-NM can significantly improve the bioavailability of BTF in rabbit corneas.

Objective:To investigate the pharmacokinetics of econazole solid lipid nanoparticles (E-SLNs) after administration of one single dose in rabbit eyes.Methods:E-SLNs with 0.2% econazole was prepared by microemulsion method.Its antifungal activity against Fusarium isolated from the eyes of patients with fungal keratitis was evaluated in vitro and was compared with natamycin eye drops.Four healthy New Zealand white rabbits were assigned to the blank control group without any drug interference during the experimental period, and other matched 21 rabbits were randomized into 7 groups according to the specimen-collected time, with 3 rabbits in each group.E-SLNs of 50 μl was singly applied to conjunctival sac in both eyes in the 21 rabbits, and tear was collected using a filter paper at 5, 15, 30, 60, 90, 120 and 180 minutes following administration of the drug.The cornea specimen was collected at above-mentioned time points respectively.The drug levels in each sample were assayed by high performance liquid chromatography.The accuracy, recovery rate, stability and antifungal activity of the drugs in tear fluid and cornea were detected.This study protocol was approved by the Life Science Ethics Review Committee of Henan Eye Hospital (No.HENNCA-2017-22). Results:For the tear samples and corneal tissue samples, the relative standard deviation ( RSD) of the accuracy of the drug was 2.34%-4.04%; the stability analysis result showed that the RSD of the drugs was less than 10%.The 50% minimum inhibitory concentration (MIC 50) and 90% minimum inhibit concentration (MIC 90) of E-SLNs were 0.37 μg/ml and 0.89 μg/ml, respectively.The MIC 50 and MIC 90 of natamycin were 1.15 μg/ml and 1.70 μg/ml, respectively.After one single dose application of E-SLNs eye drops, the peak time of the drug in tears fluids and cornea of rabbits were 5 minutes and maximum concentrations in tears and cornea were 597.64 μg/g and 33.15 μg/g, respectively. Conclusions:The drug levels in tears and cornea achieved are higher than MIC against Fusarium.

Objective To investigate the demographic characteristics, clinical features, diagnosis and treatment of patients with gout in China.Methods Clinical data of 6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or autonomous regions in China were collected and analyzed. Results (1)The ratio of male to female in patients with gout was 14.7:1.The mean age of onset was(48.8 ± 15.1)years old.Mean serum urate level was(526.7 ± 132.3)μmol/L.Patients'education background was of U-shaped distribution; (2) Hypertension was the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity[51.9%(3 536/6 814)];(3)Alcohol and high-purine food intake were dominant triggering factors in men. The diagnosis of gout was made after onset in majority of patients with cardinal symptom arthralgia.Most patients had the disease less than 5 years,and the longer the course,the more flares in the previous year of entry;(4)Febuxostat was the mostly used urate-lowering medication.20.7%(1 412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in 4 weeks, 12 weeks and 24 weeks after registration,and 18.9%(267/1 412),29.1%(215/739)and 38.1%(101/265)of them reached the control target of serum urate levels,respectively.After treatment,patients'liver function was not affected,but serum creatinine levels decreased significantly. Conclusions The proportion of gout patients who reach target serum urate level is very low.Further steps including education and survey need to be carried on.

Objective This study is aimed to investigate the possible role of Th1/Th2 cell in the pathogenesis of primary gout arthritis. Methods The peripheral blood of 21 acute gout patients (AG), 20 intermittent gout patients (IG) and 20 healthy controls (HC) were collected. The clinical data and laboratory indicators of them were enrolled. The percentages of Th1 and Th2 cells were detected by flow cytometry (FCM). The expression of GATA-3, T-bet, IL-4 and interferon (IFN)-γ mRNA in Peripheral blood mononuclear cells (PBMCs) were measured using Real time quantitative polymerase chain reaction (PCR). The protein expression levels of IL-4 and IFN-γ in serum were detected by enzyme-linked immuno sorbent assay (ELISA). The measurement data were compared by one factor analysis of variance test. The correlation between variables was used by Spearman correlation analysis. Results The percentage of Th1 cells in peripheral blood of the AG group was [(23.2 ±8.3)％], and the IG group was [(20.5 ±9.3)％], which were significantly higher (F=6.520, P<0.05) than the percentage of HC group [(14.8±3.8)％]. There was no significant difference between AG group and IG group. The percentage of Th2 cells in peripheral blood of AG group were [(1.9 ±0.7)％], which was significantly lower (F=8.267, P<0.05) than and the percentage of HC group [(3.4±1.8)％] and IG group [(3.3± 1.2)％]. There was no significant difference between the IG group and the HC group. And the proportion of TH1/Th2 cells in the AG group was higher than that of the IG group and the HC group (F=10.406, P<0.01). The expression of T-bet mRNA and IFN-γ mRNA in the AG group and IG group were higher than that in the HC group (F=4.942, P=0.010)、(F=4.458, P=0.016). However, there was no significant difference between IG group and AG group. The expression of GATA-3 mRNA and IL-4 mRNA was significantly lower (F=3.564, P=0.035) (F=5.385, P=0.007) in the AG group and IG group when compared to the HC group. And there was no significant difference between the AG and the IG group. The IFN-γ level increased in the AG and IG group compared to the HC group (F=7.659, P=0.001). The IL-4 levels in the AG group was lower (F=7.099, P=0.002) than those of the IG and HC group. Conclusion Th1 cells in the peripheral blood of patients with GA are increased and accompanied with the decrease of Th2 cells. The results of this study suggest that the imbalance of Th1/Th2 cells in the inflammatory and immune response plays a critical role in the pathogenesis of GA.

Objective To investigate the changes aad possible role of estrogen and its receptor ERα、ERβ、GPR30 in the pathogenesis of asymptomatic hyperuricemia.Methods The peripheral blood of 62 asymptomatic hyperuricemia patients (AH) and 68 healthy controls (HC) were collected.The expression of estradial (E2) in serum was detected by the chemilluminescent microparticle immunoassay (CMIA).The expression of ERα,ERβ,GPR30 mRNA in peripheral blood mononuclear cells (PBMCs) was measured using Real time quantitative polymerase chain reaction (RT-qPCR).Statistical Package form Soci-science (SPSS) 17.0 statistical software was used for data analysis.The measurement data were compared by t test,rank sum test or one factor analysis of variance test.The correlation between variables was used by Spearman correlation analysis.Results ① The expression of E2 in serum of the HC group was higher than that in the AH group [(38.7±10.2) pg/ml vs (33.7±8.6) pg/ml,Z=-0.356,P＜0.05].② The expression of ERα,GPR30 mRNA in PBMCs of HC group was increased,compared with that in the AH group (0.000 17±0.000 23 vs 0.000 12± 0.000 12,0.002 0±0.002 1 vs 0.001 5±0.000 8,Z=-2.112,-2.147,P＜0.05,respectively).No significant difference in PBMCs ERβ mRNA levels was found between HC group and AH group,while a slight but not significant increase was observed in HC group.③ The Spearman correlation analysis found that the expression of ERα and ERβ mRNA,E2 and GR,ERβ and GLU in the AH group were positively related (r=0.259,0.251,0.260,P＜0.05,respectively).Conclusion The expression of E2,ERα,ERβ,GPR30 mRNA in the peripheral blood of patients with AH is decreased,suggesting that the estrogen and its receptor may be involved in the patho-genesis of hyperuricemia.

Objective To investigate the expression profile variation of long non-coding RNAs (lncRNAs) in ankylosing sporidylitis (AS) and explore the role of lncRNAs in the pathogenesis of AS.Methods The peripheral blood mononuclear cells of AS patients and health controls (HC) were used to detect for differently expressed lncRNAs by microarray.The roles of lncRNAs were predicted with GO and pathway analysis.The results were verified by real time-polymerase chain reaction (PCR).Results A total of 148 lncRNAs and 134 mRNAs were detected,which had more than 2-fold differentially expressed in AS patients.Bioinformatics analysis found that GO term enrichment included protein binding,regulation of transcription,metabolism,signal transduction,et al.and might involve in toll-like receptor pathway,protein kinase,complement pathway,notch signaling pathway and so on.The expressions of three lncRNAs were estimated by real time-PCR which found that consistent with that of microarrays.Among these,D90064 was the most aberrantly expressed lncRNAs.Conclusions Several lncRNAs expression was changed significantly in AS patients in comparison with HC,which implies that those different lncRNAs may have an important role in the development and progression of AS.

Objective To explore the effect of paracrine extracts derived from human adipose stem cells on white matter injury of neonatal rats and to compare the difference of therapeutive effect between the cerebellum medulla oblongata pool injection and the jugular vein injection.Method A total of 73 three-day-old SD rats were chosen to establish the model of white mater injury.After 24 hours,the 73 rats were randomized into the experimental group (n =46) and the control group (n =27).Then the experimental group was reclassified into ventricular group (n =23) and intravenous group (n =23).In the ventricular group,the paracrine extracts of human adipose stem cells was injected locally into the cerebellum medulla oblongata pool injection,while the extracts was injected into the jugular vein in the intravenous group.The control group was reclassified ventricular control group (n =15) and intravenous control group (n =12),and equivoluminal saline was injected the same way as the experimental group.Frozen sections of the brain tissue from 3 rats of each experimental group one day after injection were stained with fluorescein-conjugated streptavidin to study the distribution of the extracts.The brain tissue of 3 rats from each subgroup 3 days after injection were stained with hematoxylin eosin (HE) to observe the pathomorphological changes.While 7 days later,myelin basic protein (MBP) of white matter which was obtained from 7 rats of each group was detected by immunofluorescence staining.28 days after injection,the remaining rats were assessed by neurobehavior tests.For the rats that died during the experiment,the same number of the rats would be substituted in this study.Result The paracrine extracts were found to transfer to the brain lesion area,and the amount of the extracts was more in the ventricular group.The results of the HE staining showed that the white matter injury was more severe in the ventricular control group,and extensive area of infarction were found in this group.White matter injury was mild in the experimental group,and the structure of the corpus callosum was more complete in the ventricular group.MBP semi-quantitative scores of the ventricular group (0.7 ± 0.3) and intravenous group (1.7 ± 0.3) were lower than those of ventricular control group (3.4 ± 0.4)and intravenous control group(3.3 ±0.3).And the MBP scores of ventricular group was significantly lower than that of intravenous group (P ＜ 0.05).The scores of the neurobehavioral tests of the experimental group were significantly higher than those of the control group,while the scores of the ventricular group were significantly higher than those of the intravenous group (P ＜ 0.05).Conclusion The paracrine extracts derived from adipose stem cells could improve the prognosis of white matter injury,and cerebellum medulla oblongata pool injection showed better curative effect than the jugular vein injection.

Objective To investigate the role of long noncoding RNA-AJ227913 in the pathogenesis of primary gout arthritis (GA). Methods The subjects were divided into three groups:30 acute gout patients (AGA), 30 non-acute gout patients (NAGA), 30 healthy controlsand 30 hyperuricemia patients (HUA). Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to examine the expression of AJ227913 in peripheral blood mononuclear cells(PBMCs) from four groups. 100 μg/ml monosodium urate (MSU) was used to stimulate the peripheral blood of NAGA and healthy controls patients. Then the expression ofAJ227913 was detected by RT-qPCR. Kruskal-Wallis test, Mann-Whitney test, Spearman correlations were used for statistical analysis. Results The expression level of AJ227913 in the AGA group (0.0557 ±0.0156) was higher than that in the NAGA group (0.0223±0.018) and healthy controls group (0.0038±0.0013). There was significant difference between the NAGA group and healthy controls group (P>0.05). Compared with the control group, the expression of AJ227913 in NAGA group which were stimulated by MSU was significantly increased. The Spearman correlation analysis found that the AJ227913 expression levels in GA groups were correlated with UREA (r=0.608, P<0.01), CREA (r=0.337, P<0.05), CYSC (r=0.422, P<0.01). Conclusion Altered expression of AJ227913 may be involved in the inflammatory process of GA and the balance of uricacid.

Objective: To compare the efifcacy of direct and pre-dilated atherectomy (RA) for treating the patients with calciifed coronary lesions. Methods: A total of 137 coronary artery disease (CAD) patients received RA treatment in our hospital from 2010-04 to 2014-09 were retrospectively studied. The ischemic related lesions were all deifned as calciifed coronary lesions. The patients were divided into 2 groups: Direct RA group,n=81 and Pre-dilated RA group, the patients received balloon dilatation followed by RA,n=56. The procedural features, complications, in-hospital and 1 year occurrence rates of major cardiaccerebral vascular events (MACCE) were compared between 2 groups. Results: Compared with Pre-dilated RA group, Direct RA group had the less pre-stent balloon application,P=0.000 and the higher maximum post-dilatationpressure,P=0.004; lower rate of in-operative complication (14.8% vs 32.1%),P=0.016; higher rate of acute lumen gain (128.52±75.77) % vs (77.12±27.01) %,P=0.004; lower MACCE occurrencerate(7.3% vs 23.6%) at 1 year period,P=0.006.Cox regression analysis presented that the following indexes were related to MACCE occurrence within 1 year of RA treatment: balloon dilatation before RA (HR=8.166, 95% CI 1.872-35.614,P=0.005), left main disease (HR=13.649, 95% CI 2.983-62.440,P=0.001), minimum post-operative lumen area (HR=0.583, 95% CI 0.378-0.879,P=0.010), post-dilatation (HR=0.066, 95% CI 0.013-0.332,P=0.001) and EF>40% (HR=0.019, 95% CI 0.002-0.158, P=0.000). Conclusion: Direct RA had the lower MACCE occurrence rate at 1 year period, this might be related to less operative complication and the optimal lumen gain.