Facile and Programmable Capillary-Induced Assembly of Prototissues via Hanging Drop Arrays.

An important goal for bottom-up synthetic biology is to construct tissue-like structures from artificial cells. The key is the ability to control the assembly of the individual artificial cells. Unlike most methods resorting to external fields or sophisticated devices, inspired by the hanging drop method used for culturing spheroids of biological cells, we employ a capillary-driven approach to assemble giant unilamellar vesicles (GUVs)-based protocells into colonized prototissue arrays by means of a coverslip with patterned wettability. By spatially confining and controllably merging a mixed population of lipid-coated double-emulsion droplets that hang on a water/oil interface, an array of synthetic tissue-like constructs can be obtained. Each prototissue module in the array comprises multiple tightly packed droplet compartments where interfacial lipid bilayers are self-assembled at the interfaces both between two neighboring droplets and between the droplet and the external aqueous environment. The number, shape, and composition of the interconnected droplet compartments can be precisely controlled. Each prototissue module functions as a processer, in which fast signal transports of molecules via cell-cell and cell-environment communications have been demonstrated by molecular diffusions and cascade enzyme reactions, exhibiting the ability to be used as biochemical sensing and microreactor arrays. Our work provides a simple yet scalable and programmable method to form arrays of prototissues for synthetic biology, tissue engineering, and high-throughput assays.

The Effect of Metabolic Syndrome and Its Individual Components on Renal Function: A Meta-Analysis.

BACKGROUND: Observational studies have reported inconsistent findings in the relationship between metabolic syndrome (MetS), its components, and loss of renal function, mainly including eGFR decline, new-onset CKD, and ESRD. This meta-analysis was performed to investigate their potential associations. METHODS: PubMed and EMBASE were systematically searched from their inception to 21 July 2022. Observational cohort studies in English assessing the risk of renal dysfunction in individuals with MetS were identified. Risk estimates and their 95% confidence intervals (CIs) were extracted and pooled using the random-effects approach. RESULTS: A total of 32 studies with 413,621 participants were included in the meta-analysis. MetS contributed to higher risks of renal dysfunction (RR = 1.50, 95% CI = 1.39-1.61) and, specifically, rapid decline in eGFR (RR 1.31, 95% CI 1.13-1.51), new-onset CKD (RR 1.47, 95% CI 1.37-1.58), as well as ESRD (RR 1.55, 95% CI 1.08-2.22). Moreover, all individual components of MetS were significantly associated with renal dysfunction, while elevated BP conveyed the highest risk (RR = 1.37, 95% CI = 1.29-1.46), impaired fasting glucose with the lowest and diabetic-dependent risk (RR = 1.20, 95% CI = 1.09-1.33). CONCLUSIONS: Individuals with MetS and its components are at higher risk of renal dysfunction.

Effects of Sevoflurane and Propofol on Posttraumatic Stress Disorder After Emergency Trauma: A Double-Blind Randomized Controlled Trial.

Objective: Posttraumatic stress disorder (PTSD) is a frequent and disabling consequence of traumatic events. A previous study found that early use of propofol was a potential risk factor for PTSD. This prospective study aimed to investigate the effect of propofol and sevoflurane on PTSD after emergency surgery in trauma patients. Methods: A total of 300 trauma patients undergoing emergency surgery were randomly divided into two groups and anesthetized with propofol and/or sevoflurane. Perioperative clinical data were collected. The incidence of PTSD was evaluated with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) in the two groups 1 month after the operation. The relevance of the injury time and CAPS-5 scores was assessed by Spearman correlation analysis. Logistic regression analysis was used to analyze the risk factors for PTSD. Results: The incidence of PTSD in the propofol group was higher than that in the sevoflurane group 1 month postoperatively (23.2 vs. 12.2%, P = 0.014). The injury time was negatively correlated with the CAPS-5 score in the propofol group (r = -0.226, P < 0.001). In the logistic regression analysis, the utilization of propofol was an independent risk factor for PTSD (P = 0.017). Conclusion: Early use of propofol general anesthesia in emergency surgery for trauma patients may increase the risk of PTSD. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR2100050202.

Efficacy of Intravenous Lidocaine for Pain Relief in the Emergency Department: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the efficacy of intravenous (IV) lidocaine with standard analgesics (NSAIDS, opioids) for pain control due to any cause in the emergency department. METHODS: The electronic databases of PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar were explored from 1st January 2000 to 30th March 2021 and randomized controlled trials (RCTs) comparing IV lidocaine with a control group of standard analgesics were included. RESULTS: Twelve RCTs including 1,351 patients were included. The cause of pain included abdominal pain, renal or biliary colic, traumatic pain, radicular low back pain, critical limb ischemia, migraine, tension-type headache, and pain of unknown origin. On pooled analysis, we found no statistically significant difference in pain scores between IV lidocaine and control group at 15 min (MD: -0.24 95% CI: -1.08, 0.61 I 2 = 81% p = 0.59), 30 min (MD: -0.24 95% CI: -1.03, 0.55 I 2 = 86% p = 0.55), 45 min (MD: 0.31 95% CI: -0.66, 1.29 I 2 = 66% p = 0.53), and 60 min (MD: 0.59 95% CI: -0.26, 1.44 I 2 = 75% p = 0.18). There was no statistically significant difference in the need for rescue analgesics between the two groups (OR: 1.45 95% CI: 0.82, 2.56 I 2 = 41% p = 0.20), but on subgroup analysis, the need for rescue analgesics was significantly higher with IV lidocaine in studies on abdominal pain but not for musculoskeletal pain. On meta-analysis, there was no statistically significant difference in the incidence of side-effects between the two study groups (OR: 1.09 95% CI: 0.59, 2.02 I 2 = 48% p = 0.78). CONCLUSION: IV lidocaine can be considered as an alternative analgesic for pain control in the ED. However, its efficacy may not be higher than standard analgesics. Further RCTs with a large sample size are needed to corroborate the current conclusions.

Ultrasound-guided continuous thoracic paravertebral block alleviates postoperative delirium in elderly patients undergoing esophagectomy: A randomized controlled trial.

BACKGROUND: Delirium is a common postoperative complication in older patients undergoing thoracic surgery and presages poor outcomes. Postoperative pain is an important factor in the progression of delirium. The purpose of this study was to test whether continuous thoracic paravertebral block (PVB), a more effective approach for analgesia, could decrease the incidence of delirium in elderly patients undergoing esophagectomy. METHODS: A total of 180 geriatric patients undergoing esophagectomy were randomly divided into 2 groups and treated with PVB or patient-controlled analgesia (PCA). Perioperative plasma CRP, IL-1ß, IL-6, and TNF-α levels were detected in all patients. Pain intensity was measured by a numerical rating scale. Delirium was assessed using the confusion assessment method. RESULTS: The incidence of postoperative delirium was significantly lower in the PVB group than in the PCA group. Patients in the PVB group had lower plasma CRP, IL-1ß, IL-6, and TNF-α levels and less pain when coughing after surgery. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral block improved analgesia, reduced the inflammatory reaction and decreased the occurrence of delirium after surgery.

Blocking mammalian target of rapamycin alleviates bone cancer pain and morphine tolerance via µ-opioid receptor.

The current study was to examine the underlying mechanisms responsible for the role of mammalian target of rapamycin (mTOR) in regulating bone cancer-evoked pain and the tolerance of systemic morphine. Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats and this evoked significant mechanical and thermal hyperalgesia. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) as well as phosphatidylinositide 3-kinase (p-PI3K) pathways were amplified in the superficial dorsal horn of the spinal cord of bone cancer rats compared with control rats. Blocking spinal mTOR by using rapamycin significantly attenuated activities of PI3K signaling pathways as well as mechanical and thermal hyperalgesia. Additionally, rapamycin enhanced attenuations of protein kinase Cɛ (PKCɛ)/protein kinase A (PKA) induced by morphine and further extended analgesia of morphine via µ-opioid receptor (MOR). Our data for the first time revealed specific signaling pathways leading to bone cancer pain, including the activation of mTOR and PI3K and downstream PKCɛ/PKA, and resultant sensitization of MOR. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of bone cancer pain often observed in clinics.