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To compare non-pharmacological interventions in their ability to prevent delirium in critically ill patients, and find the optimal regimen for treatment. Literature searches were conducted using PubMed, Embase, CINAHL, and Cochrane Library databases until the end of June 2019. We estimated the risk ratios (RRs) for the incidence of delirium and in-hospital mortality and found the mean difference (MD) for delirium duration and the length of ICU stay. The probabilities of interventions were ranked based on clinical outcomes. The study was registered on PROSPERO (CRD42020160757). Twenty-six eligible studies were included in the network meta-analysis. Studies were grouped into seven intervention types: physical environment intervention (PEI), sedation reducing (SR), family participation (FP), exercise program (EP), cerebral hemodynamics improving (CHI), multi-component studies (MLT) and usual care (UC). In term of reducing the incidence of delirium, the two most effective interventions were FP (risk ratio (RR) 0.19, 95% confidence interval (CI) 0.08 to 0.44; surface under the cumulative ranking curve (SUCRA) = 94%) and MLT (RR 0.43, 95% CI 0.30 to 0.57; SUCRA = 68%) compared with observation. Although all interventions demonstrated nonsignificant efficacy in regards to delirium duration and the length of the patient's stay in the ICU, MLT (SUCRA = 78.6% and 71.2%, respectively) was found to be the most effective intervention strategy. In addition, EP (SUCRA = 97.2%) facilitated a significant reduction in hospital mortality, followed in efficacy by MLT (SUCRA = 73.2%), CHI (SUCRA = 35.8%), PEI (SUCRA = 34.8%), and SR (SUCRA = 31.8%). Multi-component strategies are overall the optimal intervention techniques for preventing delirium and reducing ICU length of stay in critically ill patients by way of utilizing several interventions simultaneously. Additionally, family participation as a method of patient-centered care resulted in better outcomes for reducing the incidence of delirium. •Systematic review of different preventive nonpharmacological interventions for ICU delirium.•Multi-component strategies are overall the optimal intervention for preventing delirium and reducing ICU length of stay.•Exercise program is recommended as the preferable intervention when considering feasibility and cost-effectiveness.•Family participation proved to be a promising intervention for reducing delirium incidence, but requires further research.

To examine whether an abdominal-based early progressive mobilisation program improves gastric motility and reduces feeding intolerance in critically ill patients with endotracheal intubation. A randomised controlled trial was designed. Adult patients admitted to the intensive care unit who were intubated and had an order for enteral nutrition were randomly assigned to partake in an three stages of abdominal-based progressive mobilisation program (passive abdominal massage, bed-side bicycle and ambulating) or standard of care. Gastric antral motility was measured by bedside ultrasound. A total of 83 critically ill patients were included in the study. The intervention group displayed a statistically significant improvement in the antral motility index than the control group (p < .001), as well as in complications of feeding intolerance, including the incidence of abdominal distention (9.8% vs 33.3%, p = .009), vomiting (0% vs 16.7%, p = .019) and diarrhoea (22% vs 50%, p = .008). However, no significant difference for the full enteral feeding rate on the third day was observed between the groups.Furthermore, time on mechanical ventilation (4.52 ± 2.77 days vs 6.24 ± 3.90 days, p = .023) was shorter in intervention group, but no significant difference of length of intensive care unit stay was observed between the groups. Implementation of an abdominal-based early progressive mobilisation program can improve gastric motility and feeding intolerance in critically ill patients with an endotracheal tube.

At the present stage，China's project guarantee system is not perfect, there are problems such as the same guarantor guarantee the owner and the contractor, the risk consciousness of the construction project market is not strong, the guarantee issued by guarantee agencies is not standard, and the guarantee rate of the engineering is not unified. Such serious problems have influenced the development of China's construction market, reducing the competitiveness of China's construction enterprises in the international market. Actual survey raised a number of recommended countermeasures, such as actively carry out publicity and training work, strengthen legislation and perfect contract management, combination of compulsory and voluntary implementation, actively cultivate the professional guarantee gompanies and engineering guarantee market, perfect social credit system and social security systemm, and determine the reasonable project guarantee fees to establish a correct sense of risk, aiming to further improve our project guarantee system.

China has been experiencing an unprecedented urbanization process. In 2011, China＇s urban population reached 691 million with an urbanization rate of 51.27%. Urbaniza- tion level is expected to increase to 70% in China in 2030, reflecting the projection that nearly 300 million people would migrate from rural areas to urban areas over this period. At the same time, the total fertility rate of China＇s population is declining due to the combined effect of economic growth, environmental carrying capacity, and modern social consciousness. The Chinese government has loosened its ＂one-child policy＂ gradually by allowing childbearing couples to have the second child as long as either of them is from a one-child family. In such rapidly developing country, the natural growth and spatial migration will consistently reshape spatial pattern of population. An accurate prediction of the future spatial pattern of population and its evolution trend are critical to key policy-making processes and spatial planning in China including urbanization, land use development, ecological conservation and environ- mental protection. In this paper, a top-down method is developed to project the spatial dis- tribution of China＇s future population with considerations of both natural population growth at provincial level and the provincial migration from 2010 to 2050. Building on this, the spatial pattern and evolution trend of Chinese provincial population are analyzed. The results sug- gested that the overall spatial pattern of Chinese population will be unlikely changed in next four decades, with the east area having the highest population density and followed by central area, northeast and west area. Four provinces in the east, Shanghai, Beijing, Tianjin and Jiangsu, will remain the top in terms of population density in China, and Xinjiang, Qinghai and Tibet will continue to have the lowest density of population. We introduced an index system to classify the Chinese provinces into three categories in terms of provincial population densities Fast Changing Populated Region （FCPR）, Low Changing Populated Region （LCPR） and Inactive Populated Region （IPR）. In the FCPR, China＇s population is projected to continue to concentrate in net immigration leading type （NILT） area where receives nearly 99% of new accumulated floating population. Population densities of Shanghai, Beijing, Zhejiang will peak in 2030, while the population density in Guangdong will keep increasing until 2035. Net emigration leading type （NELT） area will account for 75% of emigration population, including Henan, Anhui, Chongqing and Hubei. Natural growth will play a dominant role in natural growth leading type area, such as Liaoning and Shandong, because there will be few emi- gration population. Due to the large amount of moving-out labors and gradually declining fertility rates, population density of the LCPR region exhibits a downward trend, except for Fujian and Hainan. The majority of the western provinces will be likely to remain relatively low population density, with an average value of no more than 100 persons per km^2.

Soft electronics are rising electronic technologies towards applications spanning from healthcare monitoring to medical implants. However, poor adhesion strength and significant mechanical mismatches inevitably cause the interface failure of devices. Herein we report a self-adhesive conductive polymer that possesses low modulus (56.1-401.9 kPa), high stretchability (700%), high interfacial adhesion (lap-shear strength >1.2 MPa), and high conductivity (1-37 S/cm). The self-adhesive conductive polymer is fabricated by doping the poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) composite with a supramolecular solvent (β-cyclodextrin and citric acid). We demonstrated the solution process-based fabrication of self-adhesive conductive polymer-based electrodes for various soft devices, including alternating current electroluminescent devices, electromyography monitoring, and an integrated system for the visualization of electromyography signals during muscle training with an array of alternating current electroluminescent devices. The self-adhesive conductive polymer-based electronics show promising features to further develop wearable and comfortable bioelectronic devices with the physiological electric signals of the human body readable and displayable during daily activities. Poor adhesion and mechanical mismatches may cause interface failure of soft devices. Here, authors report a supramolecular solvent-doped, soft, adhesive, yet conductive polymer composite for stretchable, wearable, and comfortable electronic devices.

Background The role of dexmedetomidine in preventing postoperative delirium (POD) after cardiac surgery remains controversial because of several recent trials with negative results. We aimed to perform an updated meta-analysis of randomized controlled trials (RCTs) to clarify this controversy. Methods RCTs investigating the perioperative administration of dexmedetomidine in cardiac surgery were retrieved from PubMed, Web of Science, and the Cochrane library until August,27,2020. Two researchers independently screened the literature, collected the data and evaluated the bias risk of the included studies. The meta-analysis was performed with the RevMan 5.3. Results A total of 15 studies including 2813 patients were included in the study. A pooled result showed that dexmedetomidine could reduce the risk of POD in adult population underwent cardiac surgery (OR 0.56, 95%CI 0.36–0.89, P  = 0.0004, I 2  = 64%). The subgroup analysis demonstrated that the protective effect of dexmedetomidine was only present in the patients injected with dexmedetomidine after surgery but not from the start of surgery, in the adult patients without specific age limitation but not in the elderly, and in the studies in comparison with other sedatives but not with placebo. There were no statistical differences when analyzing the secondary outcomes including hypotension (OR 1.13; 95% CI 0.54–2.37, P  < 0.00001, I 2  = 85%), bradycardia (OR 1.72; 95% CI 0.84–3.53, P  = 0.04, I 2  = 58%) and atrial fibrillation (OR 0.87; 95% CI 0.70–1.08, P  = 0.43, I 2  = 0). Conclusions Dexmedetomidine can reduce the incidence of POD compared to other sedatives and opioids after cardiac surgery in adult patients. The proper population and timing for perioperative use of dexmedetomidine after cardiac surgery remain to be further investigated.

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient’s life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects. Quercetin (Que) is a common flavonol in nature. Numerous studies have examined the therapeutic applications of Que. However, a comprehensive review of the anti-osteoporotic effects of Que has not yet been conducted. This review aimed to describe the recent studies on the anti-osteoporotic effects of Que, including its biological, pharmacological, pharmacokinetic, and toxicological properties. The outcomes demonstrated that Que could enhance OP by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity via the pathways of Wnt/β-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Thus, Que is a promising novel drug for the treatment of OP.

Autophagy, an evolutionarily conserved process, plays an important role in maintaining cellular homeostasis under physiological and pathophysiological conditions. It is widely believed that mitochondria influence the development of disease by regulating cellular metabolism. When challenged by different stimuli, mitochondria may experience morphological disorders and functional abnormalities, leading to a selective form of autophagy—mitophagy, which can clear damaged mitochondria to promote mitochondrial quality control. Sepsis is a complex global problem with multiple organ dysfunction, often accompanied by manifold mitochondrial damage. Recent studies have shown that autophagy can regulate both innate and acquired immune processes to protect against organ dysfunction in sepsis. Sepsis-induced mitochondrial dysfunction may play a pathophysiological role in the initiation and progression of sepsis-induced organ failure. Mitophagy is reported to be beneficial for sepsis by eliminating disabled mitochondria and maintaining homeostasis to protect against organ failure. In this review, we summarize the recent findings and mechanisms of mitophagy and its involvement in septic organ dysfunction as a potential therapeutic target.

Generative drug design facilitates the creation of compounds effective against pathogenic target proteins. This opens up the potential to discover novel compounds within the vast chemical space and fosters the development of innovative therapeutic strategies. However, the practicality of generated molecules is often limited, as many designs focus on a narrow set of drug-related properties, failing to improve the success rate of subsequent drug discovery process. To overcome these challenges, we develop TamGen, a method that employs a GPT-like chemical language model and enables target-aware molecule generation and compound refinement. We demonstrate that the compounds generated by TamGen have improved molecular quality and viability. Additionally, we have integrated TamGen into a drug discovery pipeline and identified 14 compounds showing compelling inhibitory activity against the Tuberculosis ClpP protease, with the most effective compound exhibiting a half maximal inhibitory concentration (IC 50 ) of 1.9 μM. Our findings underscore the practical potential and real-world applicability of generative drug design approaches, paving the way for future advancements in the field. Generative AI holds promise for creating novel compounds. Here, authors introduce TamGen, a GPT-like model designed to generate molecules tailored to specific target proteins. TamGen identified 14 potent compounds against the Tuberculosis ClpP protease, showing its potential for drug discovery.

Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.