We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Objectives: To evaluate the immunogenicity of Methods: Protein extracts from Results: Immunization with Conclusion This is the advanced study to investigate the immunogenicity of
Animals ; Antibodies, Bacterial/immunology* ; Antigens, Bacterial/immunology* ; Bacterial Proteins/immunology* ; Cross Reactions ; Cytokines/immunology* ; Female ; Genome, Bacterial ; Immunoglobulin G/immunology* ; Immunoglobulin M/immunology* ; Macrophages/immunology* ; Mice, Inbred BALB C ; Mycobacterium avium Complex/immunology* ; Mycobacterium tuberculosis/immunology* ; Tuberculosis Vaccines/administration & dosage* ; Whole Genome Sequencing

【Objective】To investigate the expression of FosB in invasive breast cancer and its correlation to the ultrasound findings and clinical significance.【Methods】Immunohistochemical and ultrasound examination were performed for 155 cases with invasive breast cancer，36 cases with paracancerous tissue and 30 cases with normal breast tissue. To investigate the correlations between the different expression of FosB with histological grade ，lymph nodes，and ultrasound findings.【Results】①The expression of FosB in paracancerous tissue and normal breast tissue was higher than that in invasive breast cancer（P＜0.01）. ②Based on immunohistochemical staining，high positive expression rate of FosB was associated with low histological grade，ER positive and PR positive（P＜0.05）. There was no correlation between FosB and age，tumor diameter，lymph nodes，Her2 and clinical stages（P＞0.05）③The expression of FosB was higher in microcalcification positive and lymph nodes bigger tissues（P＜0.05）. There was no correlation between FosB and tumor size， regular shape，boundary，posterior attenuation ratio and blood flow（P＞0.05）.【Conclusion】The expression of FosB in invasive breast cancer was lower than that in paracancerous tissue and normal breast tissue. The different expression of FosB was correlated with histological grade，ER positive and PR positive. To study the expression of FosB in invasive breast cancer may be helpful for differential diagnosis and targeted treatment. The different expression of FosB was correlated with microcalcification，lymph nodes，and combined FosB with ultrasound findings may contribute to prognostic evaluation of breast cancer.

【Objective】ToinvestigatetheexpressionandclinicalsignificanceofJunDinmolecularsubtypesofinva⁃ sivebreastcarcinoma，benignandmalignantbreastlesions.【Methods】Immunohistochemicalexaminationwasperformed for160patientswithinvasivebreastcarcinoma，191patientswithbreastintraductalproliferativelesionsand20patients withnormalbreasttissue.【Results】①ComparisonwithothersubtypesshowedthattheexpressionofJunDwassignificantly increasedinTBNCsubtype（P＜0.05）anddifferencesbetweenothersubtypeswerenotstatisticallysignificant（P＞0.05） . ②TheexpressionofJunDininvasivebreastcarcinomawaslowerthanthatinbreastintraductalproliferativelesionsand normalbreasttissuse（P <0.01） .③Basedonimmunohistochemicalstaining，highpositiveexpressionrateofJunDwas associatedwithlowhistologicalgrade（P <0.01）.ThereisnocorrelationbetweenJunDandtumordiameter，age，lymph nodes，ER，PRandhistologicalgrade（P >0.05） .【Conclusions】TheexpressionofJunDwassignificantlyincreasedin TBNCsubtype.TostudytheexpressionofJunDinTBNCsubtypeofinvasivebreastcarcinomamayprovideanevaluation intargetedtreatment.ThedifferentexpressionofJunDinbenignandmalignantbreastlesionsmaybehelpfulfortheir differentialdiagnosis.

Objective To observe the difference between continuous subcutaneous insulin infusion (CSII) at acupoint and CSII at non-acupoint in treating type 2 diabetes, for providing a novel option in selecting the insulin injection site. Method Sixty-six subjects with type 2 diabetes were randomized into a treatment group of 32 cases and a control group of 34 cases. The treatment group was intervened by CSII at acupoint, while the control group was intervened by CSII at non-acupoint. The body mass index (BMI), fasting plasma glucose (FPG), 2 h-postprandial plasma glucose (P2hPG), bedtime blood sugar, glycated hemoglobin (HbA1c), consumption of insulin, and the score of diabetes symptom grading and quantification of the two groups were compared. Result The blood sugar level, insulin consumption, HbA1c level and symptom score declined significantly after treatment in both groups (P<0.05);the BMI and initial dosage of insulin in the treatment group dropped significantly after treatment in the treatment group (P<0.05); after treatment, the BMI, FPG level, initial dosage of insulin and symptom score in the treatment group were markedly lower than those in the control group (P<0.05); there were no significant differences between the treatment group and the control group in the P2 hBG level, bedtime glucose sugar level, HbA1c level, pre-prandial insulin dose and total effective rate (P>0.05). Conclusion CSII at acupoint and at non-acupoint both can effectively improve the disease condition of type 2 diabetes. The treatment group is superior to the control group in controlling BMI and FPG, reducing the initial level of insulin, and improving the symptoms, and the treatment group presents a higher total effective rate with the increase of treatment duration compared with the control group. It is indicated that insulin infusion at abdominal acupoint has a certain advantage in the treatment of type 2 diabetes.

Objective To investigate the effects of 72 h sleep deprivation(SD)on circadian clock gene expression in the rat liver.Methods Twelve rats were randomly divided into control group and SD group.An SD instrument was used to deprive the rats′sleep for 72 h.Then the abdominal cavity was exposed to obtain liver,and the expression of clock genes was detected by RT-PCR and Western blotting analysis, respectively.Results Compared with the control group, the mRNA levels of clock,npas2 and rev-erbαstrikingly decreased in the livers of the SD group rats.However,per1,per2 and rorαmRNA levels obviously increased.bmal1 and cry1 mRNA expression hardly changed in the control and SD groups. Meanwhile,the protein levels of liver BMAL1,CLOCK,NPAS2,CRY1 and REV-ERBαwere significantly down-regulated and PER1,PER2 and RORαprotein levels were up-regulated in SD group compared with control group.Conclusion 72 h SD can result in abnormal expressions of several circadian clock genes in the rat liver at both transcriptional and translational levels.

Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.
Animals ; Biomarkers ; Chromatography, High Pressure Liquid ; methods ; Diterpenes ; toxicity ; Epoxy Compounds ; toxicity ; Glycyrrhiza ; Male ; Metabolomics ; Phenanthrenes ; toxicity ; Plant Extracts ; therapeutic use ; Principal Component Analysis ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; methods

Objective To investigate the effects of 72 h sleep deprivation (SD) on circadian clock gene expression in the rat spleen.Methods The rats were randomly divided into control group and SD group.An SD instrument was used to deprive the rats of sleep for 72 h.Then the lymphocytes from the spleen were obtained by Ficoll seperation medium before the expression of clock genes was detected by RT-PCR and Western blotting analysis respectively.Results Compared with the control group,the mRNA levels of bmal1,clock,per2 and rev-erbα strikingly decreased in the spleens of the SD group rats.However,npas2,per1,rorα and cry1 mRNA expression hardly changed in the control and SD group.Meanwhile,the protein levels of spleen BMAL1,NPAS2,CRY1 and RORα were significantly down-regulated and PER1 protein levels were up-regulated in SD group compared with control group.However REV-ERBα protein expression remained unchanged in the control and SD group.Conclusion 72 h SD can result in abnormal expressions of several circadian clock genes in lymphocytes of the spleen at both transcription and translation levels.

The amount of sulfur dioxide residue is currently employed by Chinese Pharmacopoeia (CP) as an index to screen sulfur-fumigated herbs, but it is unclear if this index can objectively reflect the quality of sulfur-fumigated herbs. In the present study, sulfur-containing derivatives were confirmed in sulfur-fumigated Moutan Cortex (MC) by UPLC-QTOF-MS/MS analysis, and the contents of sulfur-containing derivatives and sulfur dioxide residues were statistically analyzed both in self-made and commercially available sulfur-fumigated and non-fumigated MC as well as the samples thereof before and after eight-month storage. The amount of sulfur dioxide was significantly decreased, but that of the newly-generated sulfur-containing markers was not, after eight-month storage of the sulfur-fumigated MC samples, indicating that the amount of sulfur dioxide residue may not be positively correlated with the quality of sulfur-fumigated MC. Therefore, sulfur dioxide residue index alone may not objectively reflect the sulfur-fumigation extent (quality change extent) of MC, more specific method using characteristic sulfur-containing derivatives as chemical markers should be developed to supplement the sulfur dioxide residue determination in the quality control of sulfur-fumigated MC.