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.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective:To investigate the protective effect of adeno-associated virus (AAV) vector-mediated heme oxygenase-1 ( HO-1) gene overexpression on retinitis pigmentosa (RP) models in rats. Methods:Eighty healthy male SD rats were selected and randomized into the blank control group, RP model group, AAV-GFP group and AAV-HO-1-GFP group, with 20 rats in each group.The RP model was established via tail vein injection of 1% sodium iodate solution at the dose of 50 mg/kg.Rats in the RP model group, AAV-GFP group and AAV-HO-1-GFP group were subretinally injected with normal saline, AAV-GFP virus and AAV-HO-1-GFP virus according to grouping.Rats in the blank control group were administrated with subretinal injection of equal volume of normal saline.The eyeballs of rats were enucleated on 14th day after molding.The retinal structure and thickness were detected by hematoxylin-eosin staining; apoptosis in retinal tissue was detected by TUNEL assay; the expression levels of cysteinyl aspartate specific proteinase 3 (caspase 3), B-lymphoma-2 (bcl-2) and HO-1 protein in rats retina was identified by Western blot.The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology (ARVO). The study protocol was approved by an Ethics Committee of The Second Affiliated Hospital of Fujian Medical University (No.202188).Results:Hematoxylin-eosin staining results showed normal retinal structure in the blank control group, obvious retinal structure damage with thinned and wavy outer nuclear layer in the RP model group and AAV-GFP group, and mild retinal structure damage with slightly thinned outer nuclear layer in the AAV-HO-1-GFP group.Compared with the blank control group, the outer nuclear layer was significantly thinner in the RP model group and AAV-GFP group (both at P<0.05). Relative expression level of HO-1 protein in the RP model group, AAV-GFP group, and AAV-HO-1-GFP group was 0.76±0.21, 0.76±0.16, 0.92±0.05, respectively, which were all significantly higher than 0.48±0.25 in the blank control group (all at P<0.05). The relative expression level of HO-1 protein in the AAV-HO-1-GFP group was significantly higher than that in the RP model group and the AAV-GFP group (both at P<0.05). There were significant differences in apoptosis rate, the relative expression levels of bcl-2 and caspase 3 protein among the four groups ( F=1 596.333, 1 043.806, 364.331; all at P<0.01). The apoptosis rate and the relative expression level of caspase 3 were significantly higher, and the relative expression level of bcl-2 was lower in the RP model group and AAV-GFP group than those in the AAV-HO-1-GFP group (all at P<0.05). Conclusions:AAV-mediated overexpression of HO-1 gene can protect the retina of RP rats.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

OBJECTIVE: To analyze the characteristic change of fingertip vibrotactile perception threshold(VPT) at two different frequencies among mine drilling workers. METHODS: A total of 48 mine drilling workers exposed to hand-transmitted vibration for at least 1.0 year were selected from mines in Hubei Province as the vibration exposure group by using the random number table method, and workers without hand-transmitted vibration exposure were selected as the control group. An HVLab vibrotactile perception meter was used to measure the fingertip VPT at 31.5 and 125.0 Hz in workers of these two groups. RESULTS: None of the workers in these two groups showed any clinical symptoms associated with occupational hand-arm vibration diseases. At 31.5 and 125.0 Hz, the fingertip VPT in the vibration exposure group was higher than that in the control group(P<0.01), the fingertip VPT of the little fingers was higher than that of the index fingers(P<0.01). At 125.0 Hz, the fingertip VPT of the fingers in dominant hands was higher than that in non-dominant hands in workers of the vibration exposure group(P<0.01). CONCLUSION: The mine drilling workers with hand-transmitted vibration exposure had higher fingertip VPT. There were differences of VPT in fingers and dominant hands.

OBJECTIVE: To explore the effect of ultra-high frequency radiation on psychomotor neurological behavior in workers with exposure. METHODS: A total of 85 workers who exposed to 40.68 MHz radiofrequency were recruited as the exposure group by judgment sampling method. A group of 121 workers without occupational EMR exposure were recruited as the control group. Workers in both groups were from the same shoe factory. The electric field intensity(EFI) of ultra-high frequency radiation of workplace in the exposure group was measured. The computerized neurobehavioral evaluation system in Chinese version 3 was used to evaluate the psychomotor neurobehavioral function which included the neurobehavioral ability index(NAI) of simple visual reaction time(SVRT), digital screening and fit curve and the general NAI(GNAI) of the above 3 indexes. RESULTS: The median of the workplace EFI of ultra-high frequency radiation in the exposure group was 119.0 V/m, and all of them exceeded the national occupational exposure limit. NAI of digital screening in exposure group was lower than that in the control group(P<0.05). There is no statistically significant difference in the NAI of SVRT, fit curve and GNAI(P>0.05). Meanwhile, there is no statistically significant difference in abnormal rate of NAI of SVRT, digital screening, fit curve and GNAI(P>0.05). The results of multiple linear regression analysis showed that the ultra-high frequency radiation EFI exposure was negatively correlated with NAI of digital screening(P<0.05) after eliminating the influence of confounding factors such as age, working age, gender, education level, smoking, drinking and staying up late. CONCLUSION: The digital screening of psychomotor neurobehavioral function in the exposure workers was adversely affected by the ultra-high frequency radiation. The neural behavioral ability of eye-hand coordination and precise movement may be the specific performance.

Background and purpose: The technique of dynamic contrast-enhanced MRI (DCE-MRI) is widely applied in differential diagnosis between benign and malignant tumor and therapeutic estimation of neoadjuvant chemotherapy in clinic. However, there is no standard quantitative measurement method. This study aimed to assess the variability of different region of interest (ROI) selections for tumor bed of breast cancer using DCE-MRI, and to ascertain the optimal ROI delineation. Methods: We retrospectively analyzed DCE-MRI of 30 patients diagnosed with breast cancer by pathology. The ROIs were delineated by 2 different observers using iCAD software with 4 methods, including whole tumor (Whole), the slice containing the most enhancing voxels (SliceMax), 3 slices centered in SliceMax (Partial) and the 5％ most enhancing contiguous voxels within SliceMax (5Max), to generate the volume transfer constant (Ktrans), the extracellular volume fraction (Ve) and rate constant (Kep). And the reproducibilities of the measurements were assessed using the Bland-Altman method. Results: In the analysis of ROIs delineation, the Ktrans, Ve and Kep reported by different observers were 1.26±0.54 vs 1.25±0.53, 0.75±0.23 vs 0.73±0.22 and 1.93±1.46 vs 1.95±1.51 (P＞0.05) using the method of Whole, and 1.28±0.43 vs 1.26±0.43, 0.74±0.21 vs 0.80±0.27, 1.95±1.53 vs 1.93±1.43 (P＞0.05) using the method of Partial, and 1.30±0.33 vs 1.32±0.33, 0.77±0.20 vs 0.73±0.24, 1.82±1.53 vs 1.87±1.45 (P＞0.05) using the method of SliceMax, and 1.31±0.35 vs 1.35±0.33, 0.77±0.20 vs 0.98±0.25, 1.97±1.36 vs 1.73±1.55 using the method of 5Max (P＜0.05). Using the methods of ROI delineation except 5Max, there was no significant difference between Ktrans, Ve and Kep reported by different observers. The bias vs limits of agreement were 0.002 vs-0.013 to 0.012,-0.003 vs-0.023 to 0.017, 0.006 vs-0.018 to 0.029,-0.035 vs-0.054 to 0.018 measured with Whole method, SliceMax, Partial and 5Max respectively using the Bland-Altman method. Conclusion: It may be reliable to measure functional parameters of primary tumors in breast cancer using DCE-MRI according to the methods of Whole, Partial and SliceMax.

Objective To analyze the changes of levels of plasma diamine oxidase(DAO),D-lactate and endotoxin in children with different severity of hand-foot-mouth disease(HFMD),explore the changes of the function of intestinal mucosal barrier in children with HFMD,and investigate the sensitivity and early warning effect of the indexes described previously on the damage of intestinal mucosal barrier in children with severe HFMD.Methods Four hundred and seventy inpatient children in Xi′an Children′s Hospital from March 2016 to June 2017 suffered from HFMD were selected as the study group,and one hundred healthy children were selected as the control group in the same period.Children in the study group were divided into common group(n=300),severe group(n=110)and critical condition group(n=60)according to the sever-ity of the disease.The levels of plasma DAO,D-lactate and endotoxin from children in each group were com-pared.Results The plasma D-lactate level of the children in the study group was significantly higher than that in the control group,and the difference was statistically significant[(27.670 ± 6.273)mg/L vs.(25.585 ± 5.177)mg/L;t=3.515,P<0.05];but the differences of DAO and endotoxin compared with the control group were not statistically significant[(3.205 ± 0.956)U/L vs.(3.135 ± 0.884)U/L,P>0.05;(1.186 ± 0.486)U/L vs.(1.091 ± 0.494)U/L,P>0.05].The comparison of multiple groups showed that the differ-ence of plasma D-lactate levels was statistically significant(F=33.488,P<0.05),while the differences of the levels of DAO and endotoxin were not statistically significant among different severity groups(F=0.709, F=2.296,P>0.05).The level of plasma D-lactate in critical condition group[(32.502 ± 4.756)mg/L]was significantly higher than those in the severe group[(29.872 ± 6.468)mg/L],the common group [(25.896 ± 5.691)mg/L] and the control group,and the differences were statistically significant(P <0.05);the difference in plasma D-lactate levels in the severe and non-severe groups was statistically signifi-cant(P<0.05),and the difference between common group and control group was not statistically significant (P>0.05).Conclusion The intestinal permeability and intestinal mucosal barrier are impaired in children with severe and critical HFMD.Plasma D-lactate is significantly elevated in the early stage of intestinal barri-er injury.Compared with DAO and endotoxin,D-lactate is a sensitive and early warning index suggesting the impaired intestinal mucosal barrier function in severe and critical cases of HFMD.

Objective To study the role of mesenchymal stem cells (MSC) in an animal model combining ischemia-reperfusion with 85％ liver resection.Methods Eight-week-old male SD rats received BM-MSC by tail vein and then underwent 30-min ischemia followed by 85％ liver resection.The survival rate was monitored for 7 days after surgery.Liver regeneration was assessed on day 2 after hepatectomy.Liver damage,liver cell apoptosis,and cytokine expression in the first 24 h after hepatectomy were also assessed.Results BM-MSC mostly homed to the spleen.Transplantation significantly inhibited myeloperoxidase [(19.9 ± 6.0) mg/g vs.(41.4 ± 10.2) mg/g] and downregulated proinflammatory cytokines.BM-MSC significantly reduced the ALT and AST levels [AST (1 475 ± 275) IU/L vs.(2 550 ± 441) IU/L,P ＜ 0.05;ALT (738 ± 101) IU/L vs.(1 113 ± 268) IU/L,P ＜ 0.05].The attenuation of liver injury was also verified histologically 24 h after surgery.Liver cell apoptosis was markedly reduced.Moreover,BM-MSC infusion significantly promoted remnant liver regeneration.As a result,the survival rate was improved by BM-MSC treatment in this model (95％ vs 70％,P ＜ 0.05).Conclusion In an animal model combining ischemia-reperfusion with 85％ liver resection,BM-MSC infusion attenuated liver injury and promoted hepatocyte regeneration,resulting in improved survival rate.