Expert consensus on late stage of critical care management / 中华内科杂志

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.

Effect of Focused Cardiac Ultrasound in Combination with Lung Ultrasound on Critically Ill Patients: A Multicenter Observational Study in China / 中国医学科学杂志(英文版)

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%

Regulatory mechanism of heat shock protein 90 on autophagy-related transcription factor EB in human hepatocellular carcinoma cells / 生理学报

This study was aimed to investigate the regulatory mechanism of heat shock protein 90 (Hsp90) on transcription factor EB (TFEB) during autophagy in liver cancer cells. Human hepatocellular carcinoma cell line HepG2 was treated with Hsp90 N- and C-terminal inhibitors (STA9090 and Novobiocin), respectively. Western blot and RT-PCR were used to detect the expression levels of TFEB and autophagy-related proteins. Chromatin immunoprecipitation (ChIP) assay was used to observe the ability of Hsp90α binding to the TFEB proximal promoter region. The double-luciferase gene reporter experiment was used to determine the activity of TFEB promoter. The results showed that hypoxia induced up-regulation of TFEB protein and mRNA expression levels in the HepG2 cells. The protein expression levels of TFEB, LC3 and P62 were down-regulated significantly by either STA9090 or Novobiocin, under both normoxic and hypoxic conditions. Transfection of Hsp90α-overexpressing plasmids up-regulated TFEB protein levels in either wild-type or Hsp90α knockout HepG2 cells. Hsp90 bound to the TFEB proximal promoter region and was involved in regulating TFEB transcriptional process. Whereas both STA9090 and Novobiocin inhibited Hsp90 to bind to the TFEB proximal promoter region, and decreased the activity of TFEB promoter. These results suggest that Hsp90 promotes TFEB transcription in human hepatocellular carcinoma cells by binding to the proximal promoter region, thereby up-regulating the expression levels of autophagy-related proteins.

Focus on the hotspots of CRRT / 天津医药

With the progress of technology and the development of severe kidney medicine, continuous renal replacement therapy (CRRT) has been extended to kidney support and has been widely used for aiming to rapidly correct fatal complications of several life-threatening renal impairment (AKI). However, there are many controversies and problems, including the timing of initiating CRRT, the dosage of treatment and the choice of filter membrane material for different kinds of critically ill patients. The controversy and study of 60 years have not come to a unanimous conclusion, which reflects the critically clinical complexity. There is no "unchangeable (one size fits all)" treatment model, but rather a "patient-centered, individualized, precision CRRT" treatment. This article was to explore these three hotspots in order to provide more evidences for clinicians to perform rationalized, personalized and precise CRRT, and to make more patients benefit from CRRT.

Temporal and spatial changes of α7nAChR and nNOS in cerebral cortex and hippocampus of Aβ-induced cognitive dysfunction rats / 生理学报

The present study was to explore the temporal and spatial distributions and variations of α7 nicotinic acetylcholine receptor (α7nAChR) and neuronal nitric oxide synthetase (nNOS) in cerebral cortex and hippocampus of Aβ-induced cognitive dysfunction rats. Sixty Sprague-Dawley (SD) rats were randomly divided into six groups. Three experimental groups were intracerebroventricularly (i.c.v.) injected with condensed-amyloid beta peptides 1-42 (Aβ, 2.5 µg/µL, 4 µL) and were observed on day 7 (7 d Aβ group), day 14 (14 d Aβ group) and day 21 (21 d Aβ group), respectively. Three control groups were i.c.v. injected with equivalent volume of normal saline and observed at the same time points as the experimental groups. The learning and memory abilities of rats were tested with Y-maze; the locations and protein expression levels of α7nAChR and nNOS in cerebral cortex and hippocampal CA1, CA3, DG regions were measured by immunohistochemistry and Western blot, respectively. The result showed that, compared with the control groups, the three experimental groups exhibited decreased learning and memory behavioral abilities, and down-regulated expressions of nNOS and α7nAChR in prefrontal cortex and hippocampal regions, especially in superficial layer of prefrontal cortex and hippocampal CA3 region. Comparisons among the three experimental groups showed that the inhibitory effects of Aβ on the abilities of learning and memory and the expressions of α7nAChR and nNOS in prefrontal cortex and hippocampus were time dependent. The results suggest that the coincident declines of α7nAChR and nNOS in prefrontal cortex and hippocampus may be the foundations of the cognitive dysfunction.

The synergetic effects of nitric oxide and nicotinic acetylcholine receptor on learning and memory of rats / 生理学报

The aim of the present study is to explore the interaction of nitric oxide (NO) and nicotinic acetylcholine receptor (nAChR) on learning and memory of rats. Rats were intracerebroventricularly (i.c.v.) injected with L-arginine (L-Arg, the NO precursor) (L-Arg group) or choline chloride (CC, an agonist of α7nAChR) (CC group), and with combined injection of L-Arg and CC (L-Arg+CC group), and methyllycaconitine (MLA, α7nAChR antagonist) or N(ω)-nitro-L-arginine methylester (L-NAME, nitric oxide synthase inhibitor) i.c.v. injected first and followed by administration of L-Arg combined with CC (MLA+L-Arg+CC group or L-NAME+L-Arg+CC group), respectively, and normal saline was used as control (NS group). The learning and memory ability of rats was tested with Y-maze; the level of NO and the expressions of neuronal nitric oxide synthase (nNOS) or α7nAChR in hippocampus were measured by NO assay kit, immunohistochemistry or Western blot. The results showed that compared with L-Arg group or CC group, the rats' learning and memory behavioral ability in Y-maze was observably enhanced and the level of NO, the optical density of nNOS-like immunoreactivity (LI) or α7nAChR-LI in hippocampus were significantly increased in L-Arg+CC group; Compared with L-Arg+CC group, the ability of learning and memory and the level of NO as well as the expressions of nNOS-LI or α7nAChR-LI were obviously decreased in MLA+L-Arg+CC group or in L-NAME+L-Arg+CC group. In conclusion, i.c.v. administration of L-Arg combined with CC significantly improved the action of the L-Arg or CC on the content of NO and the nNOS or α7nAChR expressions in hippocampus along with the learning and memory behavior of rats; when nNOS or α7nAChR was interrupted in advance, the effects of L-Arg combined with CC were also suppressed. The results suggest that there are probably synergistic effects between NO and nAChR on learning and memory.

Quantitative assessment of bladder neck compliance by using transvaginal real-time elastography of women.

To assess the feasibility of using ultrasound real-time elastography (RTE) to measure bladder neck compliance, we performed real-time elastography measurements by manually applying repetitive compression with the transducer on the scan position of the bladder neck. Instant elastography index (EI) and mean EI of anterior and posterior lips of the bladder neck were calculated. The EI values of anterior and posterior lips of the bladder neck were analyzed in relation to age, body surface area, body mass index, detrusor wall thickness and length, width and thickness of the bladder neck in healthy women. The intra-observer and inter-observer repeatability of measurements in different parts of the bladder neck were assessed using intra-class correlation coefficients with 95% confidence intervals and Bland-Altman analysis. There were no statistically significant differences between elastography measurements made by the same or two different observers in each area measured. There was no significant difference between anterior and posterior lip thickness of the bladder neck. The distribution of the elastography measurements indicated that the anterior lip of the bladder neck was slightly harder than the posterior lip. On the whole, from the results of the study, it was clear that EIs of the bladder neck were related to age in healthy women. Stepwise multiple regression analysis results revealed that age was the only independent factor modulating compliance of the bladder neck in healthy women. It is possible to provide a reproducible semi-quantification of real-time elastography in bladder neck compliance.

TLR4 mediates MAPK-STAT3 axis activation in bladder epithelial cells.

The role of Toll-like receptor 4 (TLR4) in immune cells is well characterized, but its biological properties in bladder epithelial cells (BECs), especially reciprocal crosstalk between mitogen-activated protein (MAP) kinase pathway and signal transducer and activator of transcription (STAT)3-mediated signal transduction elicited by TLR4 have not been demonstrated so far. The present studies were to demonstrate the signal transduction and inflammatory cytokine response elicited through activation of TLR4 in BECs with a special focus on the crosstalk between the MAPK-pathway and STAT3-mediated signals and its regulatory relevance for the inflammatory response towards lipopolysaccharide (LPS). We selected human bladder cancer T24 cell line in the present study and examined its expression of TLR4 by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The expression of p38, extracellular signal regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and STAT3 were performed by RT-PCR, quantitative PCR, and Western blotting. Signal transduction was analyzed by Western blotting. Interleukin-6 (IL-6) and interleukin-10 (IL-10) secretion in culture supernatants were tested by human enzyme-linked immunosorbent assay (ELISA) kit. BECs of rat infection in vivo model and patients with cystitis glandularis (CG) were analyzed as described above. Our study demonstrated that TLR4 was significantly upregulated following LPS treatment, with the maximum mRNA expression occurring at 4 h after stimulation. Activation of TLR4 signaling by LPS resulted in phosphorylation of MAPK and STAT pathways and upregulation of IL-10 in dose- and time-dependent manners in T24 cells. Pretreatment of cells with SB203580 (inhibitor of p38) and SP600125 (inhibitor of JNK) attenuated LPS-induced IL-10 expression, whereas it markedly inhibited the STAT3 expression. IL-10 mRNA expression was increased in inflamed lesions compared to noninflamed tissue in rats and patients with CG disease. Our results demonstrate that activation of TLR4 signaling in BECs induces IL-10 expression via activation of p38 and JNK, and the activation of STAT-3 was upregulated. Our data indicated that the reciprocal crosstalk between the MAPK pathway and STAT3-mediated signal transduction forms a critical axis successively activated by LPS in BECs.

Clinical application of IPS-empress 2 pressable all-ceramic crowns / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical prosthetic effect of IPS-Empress 2 pressahie ceramic crowns.</p><p><b>METHODS</b>198 teeth of 70 patients were restored with IPS-Empress 2 pressahie ceramic crowns. The patients were asked to return in one week and every half year. The clinical prosthetic effect was evaluated.</p><p><b>RESULTS</b>Through follow-up of 3-38 months, the veneer porcelain crowns of 3 teeth were broken. 2 crowns fall off due to teeth fracture, gingivitis occurred in 2 teeth, pulpitis or periapical periodontitis occurred in 3 teeth. The shades of 3 crowns were darkening. The prosthetic effect of 185 teeth was satisfied. The rate of satisfaction was 93.4%.</p><p><b>CONCLUSION</b>IPS-Empress 2 pressable all-ceramic crown has the advantages of aesthetic effect, good hiocompatihility and simple fabrication. But its strength is not enough for posterior teeth and it can not cover the deep color of non-vital teeth and metal materials.</p>

Expression of Thraustochytrium sp.FJN-10 ?~4-Desaturase Gene in Saccharomyces cerevisiae / 微生物学通报

1.6 kb ?4-desaturase gene(FAD4)was amplified by PCR using plasmid pGEM-TFAD4 as template.The fragment was subcloned into the HindⅢ/XbaⅠrestriction site of pYES2.0 vector.Recombinant plasmid pYFAD4 was transformed into Saccharomyces cerevisiae strain INVScl for expression.It was found to exhibit ?4-fatty acid desaturase activity in the recombinant S.cerevisiae YFAD4 in the presence of exogenous fatty acid substrate docosapentaenoic acid(100?mol/L)under introduction of GAL1.Expression of the FAD4 under appropriate media and temperature conditions led to the production of DHA and it reached 41.13% of the total yeast fatty acid by GC detection.It was suggested that the protein encoded by FAD4 could specifically catalyze DPA into DHA.