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

Phosphodiesterase-4 (PDE4) functions as a catalyzing enzyme targeting hydrolyzation of intracellular cyclic adenosine monophosphate (cAMP) and inhibition of PDE4 has been proven to be a competitive strategy for dermatological and pulmonary inflammation. However, the pathological role of PDE4 and the therapeutic feasibility of PDE4 inhibitors in chronic ulcerative colitis (UC) are less clearly understood. This study introduced apremilast, a breakthrough in discovery of PDE4 inhibitors, to explore the therapeutic capacity in dextran sulfate sodium (DSS)-induced experimental murine chronic UC. In the inflamed tissues, overexpression of PDE4 isoforms and defective cAMP-mediating pathway were firstly identified in chronic UC patients. Therapeutically, inhibition of PDE4 by apremilast modulated cAMP-predominant protein kinase A (PKA)-cAMP-response element binding protein (CREB) signaling and ameliorated the clinical symptoms of chronic UC, as evidenced by improvements on mucosal ulcerations, tissue fibrosis, and inflammatory infiltrations. Consequently, apremilast maintained a normal intestinal physical and chemical barrier function and rebuilt the mucosal homeostasis by interfering with the cross-talk between human epithelial cells and immune cells. Furthermore, we found that apremilast could remap the landscape of gut microbiota and exert regulatory effects on antimicrobial responses and the function of mucus in the gut microenvironment. Taken together, the present study revealed that intervene of PDE4 provided an infusive therapeutic strategy for patients with chronic and relapsing UC.

Objective: To study the clinical pathological characteristics, immunophenotype, molecular changes and prognosis of the papillary renal neoplasm with reverse polarity (PRNRP). Methods: Nine cases of PRNRP, diagnosed from 2013 to 2019, were retrieved from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histomorphology, immunophenotype and molecular genetics were analyzed with review of the literatures. Results: There were five male and four female patients, aged from 49 to 70 years, with an average age of 60.1 years. During a mean follow-up of 29 months, one patient died for other cause, and the others survived without disease. Microscopically, the tumor cells arranged in papillary structure with a fibrovascular core, the surface of which was covered with a single layer of cuboidal or columnar cells. The most prominent feature was that the tumor nuclei located at the top of the cytoplasm far from the basement membrane, and they were monotonous in size and arranged neatly with no or few nucleoli. Immunohistochemically, all nine cases of PRNRP showed diffuse positive expression of CK7 and E-cadherin, various degrees of P504s expression, and no expression of CD10 and CD117, with a Ki-67 index of 1%-3%. Unlike other papillary renal cell carcinoma, the nine cases of PRNRP all showed characteristic positive expression of GATA3. The fluorescence in situ hybridization assay showed that the majority of PRNRPs (8/9) did not have triploids on chromosomes 7 and 17. The sequencing of the KRAS gene confirmed the presence of a nonsense KRAS mutation in 8 of the 9 cases. Conclusions: PRNRP is a subtype of papillary renal cell carcinoma with characteristic morphological, immunophenotypic and molecular features, and indolent behaviors. More data are needed to define PRNRP as "carcinoma", and a definitive diagnosis of PRNRP is of great significance for proper treatment choice and accurate prognostication.
Biomarkers, Tumor ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney ; Kidney Neoplasms/genetics* ; Male ; Middle Aged ; Prognosis

Humans ; Liposarcoma/genetics* ; Liposarcoma, Myxoid/genetics* ; Transcription Factor CHOP/genetics*

Objective: miR-663a has been reported to be downregulated by X-ray irradiation and participates in radiation-induced bystander effect via TGF-β1. The goal of this study was to explore the role of miR-663a during radiation-induced Epithelium-to-mesenchymal transition (EMT). Methods: TGF-β1 or IR was used to induce EMT. After miR-663a transfection, cell migration and cell morphological changes were detected and the expression levels of miR-663a, TGF-β1, and EMT-related factors were quantified. Results: Enhancement of cell migration and promotion of mesenchymal changes induced by either TGF-β1 or radiation were suppressed by miR-663a. Furthermore, both X-ray and carbon ion irradiation resulted in the upregulation of TGF-β1 and downregulation of miR-663a, while the silencing of TGF-β1 by miR-663a reversed the EMT process after radiation. Conclusion Our findings demonstrate an EMT-suppressing effect by miR-663a via TGF-β1 in radiation-induced EMT.
Down-Regulation ; Epithelial-Mesenchymal Transition ; Epithelium/metabolism* ; MicroRNAs/metabolism* ; Transforming Growth Factor beta1/pharmacology*

Panacis Quinquefolii Radix is the dry root of Panax quinquefolium, which is a perennial plant of Araliaceae. The plant has a long growth cycle and serious growth barrier problem, which leads to the use of pesticides. As a result, the pesticide residues in Panacis Quinquefolii Radix are arousing great concern. This paper reviews the research findings on the investigation, detection methods, content analysis and risk assessment of pesticide residues in Panacis Quinquefolii Radix since 1993, and compares the pesticide residue limit standards of different countries and regions. The pesticide residues in Panacis Quinquefolii Radix have been changing from organochlorines with high toxicity to triazines and triazoles with low toxicity. The pesticide residues are generally low, while the pollution of pentachloronitrobenzene and other pesticides still exist. The detection method has evolved from chromatography to chromatography-mass spectrometry. There are no reports of health risks caused by pesticide residues of Panacis Quinquefolii Radix. Pesticide residue is a major factor restricting the sound development of Panacis Quinquefolii Radix industry in China. Therefore, we suggest to improve the registration of pesticides applied to the plant, popularize mature ecological planting mode and supporting technology, and strengthen the research on the risk assessment and limit standard of pesticide residue in Panacis Quinquefolii Radix.
Drugs, Chinese Herbal/chemistry* ; Ginsenosides/analysis* ; Mass Spectrometry ; Panax/chemistry* ; Pesticide Residues/analysis*

Lonicera Japonica Flos is the dried bud or nascent flower of Lonicera japonica(Caprifoliaceae). The plant suffers from various diseases and pests in the growth period and thus pesticides are often used. As a result, the resultant pesticide residues in Lonicera Japonica Flos have aroused great concern. This review summarized the investigation, detection methods, content analysis, and risk assessment of pesticide residues in Lonicera Japonica Flos since 1996, and compared the maximum residue limits among different countries and regions. The results showed that the pesticide residues were detected in Lonicera Japonica Flos from different production areas, and only some exceeded the limits. The residual pesticides have changed from organochlorines to new types such as tebuconazole and nitenpyram. The detection method has upgraded from chromatography to chromatography-mass spectrometry. Most pesticide residues will not cause health risks, except carbofuran. Pesticide residues limit the development of Lonicera Japonica Flos industry in China. In practice, we should improve the drug registration of Lonicera Japonica Flos, promote ecological prevention and control technology, and formulate and promote pesticide residue limit standard of Lonicera Japonica Flos.
Flowers/chemistry* ; Lonicera/chemistry* ; Mass Spectrometry ; Pesticide Residues/analysis* ; Pesticides/analysis*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Background::The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years.Methods::The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population.Results::The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine.Conclusions::Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD.

Objective:To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China.Methods:A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia.Results:A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95% CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95% CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion:Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.