The impact of perioperative ketamine or esketamine on the subjective quality of recovery after surgery: a meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to evaluate the impact of ketamine/esketamine on postoperative subjective quality of recovery (QoR). METHODS: MEDLINE, Embase, Cochrane library, and Google Scholar were searched for randomised controlled trials (RCTs) that examined the impacts of perioperative ketamine/esketamine use and postoperative QoR. The primary outcome was subjective QoR (QoR-9, QoR-15, QoR-40) on postoperative day (POD) 1-3, whereas the secondary outcomes included pain severity, anxiety scores, depression scores, risk of adverse events (i.e. nausea, vomiting, dizziness, drowsiness), and length of stay. RESULTS: The analysis included 18 RCTs (1554 participants; ketamine: seven trials, esketamine: 11 trials), of which 15 were conducted in China. Ketamine/esketamine improved the QoR scores on PODs 1 and 2 compared with the control (standardised mean difference [SMD]: 0.63, P<0.0001 for POD 1; SMD: 0.56, P=0.04 for POD 2), without beneficial effect on POD 3. Subgroup analyses revealed significant differences in QoR scores on POD 1 by regimen (SMD: esketamine 1.14, ketamine 0.01) and country (SMD: China 0.82, other countries -0.21). The emotional domain of QoR was improved from PODs 1 to 3, whereas the other domains were only improved on POD 1. Lower postoperative anxiety (SMD: -0.48, P=0.003) and depression (SMD: -0.72, P=0.001) scores were also observed with ketamine/esketamine use. Furthermore, pain severity was reduced on PODs 1 and 2, with no difference in the risk of adverse events or length of stay. CONCLUSIONS: This meta-analysis demonstrated that ketamine/esketamine use in the perioperative period is associated with improved early subjective QoR, pain severity, and psychological symptoms without an increase in the likelihood of adverse events. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023477580).

Prediction of early postoperative pain using sleep quality and heart rate variability.

PURPOSE: Accurate predictions of postoperative pain intensity are necessary for customizing analgesia plans. Insomnia is a risk factor for severe postoperative pain. Moreover, heart rate variability (HRV) can provide information on the sympathetic-parasympathetic balance in response to noxious stimuli. We developed a prediction model that uses the insomnia severity index (ISI), HRV, and other demographic factors to predict the odds of higher postoperative pain. METHODS: We recruited gynecological surgery patients classified as American Society of Anesthesiologists class 1-3. An ISI questionnaire was completed 1 day before surgery. HRV was calculated offline using intraoperative electrocardiogram data. Pain severity at the postanesthesia care unit (PACU) was assessed with the 0-10 numerical rating scale (NRS). The primary outcome was the model's predictive ability for moderate-to-severe postoperative pain. The secondary outcome was the relationship between individual risk factors and opioid consumption in the PACU. RESULTS: Our study enrolled 169 women. Higher ISI scores (p = 0.001), higher parasympathetic activity (rMSSD, pNN50, HF; p < 0.001, p < 0.001, p < 0.001), loss of fractal dynamics (SD2, alpha 1; p = 0.012, p = 0.039) in HRV analysis before the end of surgery were associated with higher NRS scores, while laparoscopic surgery (p = 0.031) was associated with lower NRS scores. We constructed a multiple logistic model (area under the curve = 0.852) to predict higher NRS scores at PACU arrival. The five selected predictors were age (OR: 0.94; p = 0.020), ISI score (OR: 1.14; p = 0.002), surgery type (laparoscopic or open; OR: 0.12; p < 0.001), total power (OR: 2.02; p < 0.001), and alpha 1 (OR: 0.03; p < 0.001). CONCLUSION: We employed a multiple logistic regression model to determine the likelihood of moderate-to-severe postoperative pain upon arrival at the PACU. Physicians could personalize analgesic regimens based on a deeper comprehension of the factors that contribute to postoperative pain.

Visualization Analysis of Artificial Intelligence Literature in Forensic Research.

OBJECTIVES: To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database, to explore research hotspots and developmental trends. METHODS: A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the literature measuring tool CiteSpace. The authors, institution, country (region), title, journal, keywords, cited references and other information of relevant literatures were analyzed. RESULTS: A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries (regions) were identified, with the number of articles published showing an increasing trend year by year. Among them, the United States had the highest number of publications and China ranked the second. Academy of Forensic Science had the highest number of publications among the institutions. Forensic Science International, Journal of Forensic Sciences, International Journal of Legal Medicine ranked high in publication and citation frequency. Through the analysis of keywords, it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technology for sex and age estimation, cause of death analysis, postmortem interval estimation, individual identification and so on. CONCLUSIONS: It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research. Exploring the combination of advanced artificial intelligence technologies with forensic research will be a hotspot and direction for future research.

Impact of intravenous and topical lidocaine on clinical outcomes in patients receiving propofol for gastrointestinal endoscopic procedures: a meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of i.v. or topical lidocaine as an anaesthesia adjunct in improving clinical outcomes in patients receiving gastrointestinal endoscopic procedures under propofol sedation remains unclear. METHODS: Electronic databases (MEDLINE, EMBASE, and Cochrane Library) were searched for RCTs comparing the clinical outcomes with or without lidocaine application (i.v. or topical) in patients receiving propofol for gastrointestinal endoscopic procedures from inception to 29 March 2021. The primary outcome was propofol dosage, while secondary outcomes included procedure time, recovery time, adverse events (e.g. oxygen desaturation), post-procedural pain, and levels of endoscopist and patient satisfaction. RESULTS: Twelve trials (1707 patients) published between 2011 and 2020 demonstrated that addition of i.v. (n=7) or topical (n=5) lidocaine to propofol sedation decreased the level of post-procedural pain (standardised mean difference [SMD]=-0.47, 95% confidence interval [CI]: -0.8 to -0.14), risks of gag events (risk ratio [RR]=0.51, 95% CI: 0.35-0.75), and involuntary movement (RR=0.4, 95% CI: 0.16-0.96). Subgroup analysis demonstrated that only i.v. lidocaine reduced propofol dosage required for gastrointestinal endoscopic procedures (SMD=-0.83, 95% CI: -1.19 to -0.47), increased endoscopist satisfaction (SMD=0.75, 95% CI: 0.21-1.29), and shortened the recovery time (SMD=-0.83, 95% CI: -1.45 to -0.21). Intravenous or topical lidocaine did not affect the incidence of oxygen desaturation (RR=0.72, 95% CI: 0.41-1.24) or arterial hypotension (RR=0.6, 95% CI: 0.22-1.65) and procedure time (SMD=0.21, 95% CI: -0.09 to 0.51). CONCLUSION: This meta-analysis demonstrated that i.v. or topical lidocaine appears safe to use and may be of benefit for improving propofol sedation in patients undergoing gastrointestinal endoscopic procedures. Further large-scale trials are warranted to support our findings.

Interferon-ß suppresses inflammatory pain through activating µ-opioid receptor.

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-ß has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-ß in reducing mechanical allodynia caused by Complete Freund's Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-ß in naïve rats and the rats with CFA-induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-ß in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-ß antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-ß is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-ß at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-ß produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-ß injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/ßR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-ß is through µ-opioid receptors activation in spial cord.

[Bacterial culture of donor semen: Analysis of results from 2008 to 2018].

OBJECTIVE: To investigate the distribution of pathogenic bacteria in donor semen and the effect of bacterial infection on semen quality. METHODS: We performed bacterial culture on and counted the bacterial colonies (BC) in the semen samples collected from 4 897 sperm donors from 2008 to 2018 and divided them into groups A (BC <104 cfu/ml, n = 4 229), B (BC ≥104 cfu/ml, n = 150) and C (BC = 0 cfu/ml, n = 518). Using the biochemical reaction system of the French Biological Merry Emmanuel Company, we identified the bacterial species in group B, subjected all the semen samples to SCA computer assisted semen analysis, and compared the semen quality among different groups. RESULTS: In the 4 897 semen samples, hybrid bacterial contamination was found in 6 (0.12%) and non-hybrid bacteria in 4 379 (89.42%), including 150 (3.43%) in group B. In the semen samples with BC ≥104 cfu/ml, Gram-negative (G－) bacteria were observed in 104 (69.33%), mainly including Escherichia coli, followed by Proteusbacillus vulgaris and Enterobacteria, Gram-positive cocci (G+) in 39 (26.00%), G－ bacteria in 4 (2.67%) and Neisseria gonorrhoeae in 3 (2.00%). Compared with group C, groups A and B showed remarkably reduced total sperm count (P < 0.05) and percentage of progressively motile sperm (P < 0.05) but no statistically significant differences in the semen liquefaction time, semen PH value, total sperm motility or the percentage of morphologically normal sperm (P > 0.05). CONCLUSIONS: Bacterial culture of donor semen revealed a positive rate of 89.42% and varied the bacterial species, mainly including G－ bacteria. And the semen quality decreased with the increase of bacterial colonies.

Structures of bacterial polynucleotide kinase in a Michaelis complex with GTP•Mg2+ and 5'-OH oligonucleotide and a product complex with GDP•Mg2+ and 5'-PO4 oligonucleotide reveal a mechanism of general acid-base catalysis and the determinants of phosphoacceptor recognition.

Clostridium thermocellum polynucleotide kinase (CthPnk), the 5' end-healing module of a bacterial RNA repair system, catalyzes reversible phosphoryl transfer from an NTP donor to a 5'-OH polynucleotide acceptor. Here we report the crystal structures of CthPnk-D38N in a Michaelis complex with GTP•Mg(2+) and a 5'-OH oligonucleotide and a product complex with GDP•Mg(2+) and a 5'-PO4 oligonucleotide. The O5' nucleophile is situated 3.0 Å from the GTP γ phosphorus in the Michaelis complex, where it is coordinated by Asn38 and is apical to the bridging ß phosphate oxygen of the GDP leaving group. In the product complex, the transferred phosphate has undergone stereochemical inversion and Asn38 coordinates the 5'-bridging phosphate oxygen of the oligonucleotide. The D38N enzyme is poised for catalysis, but cannot execute because it lacks Asp38-hereby implicated as the essential general base catalyst that abstracts a proton from the 5'-OH during the kinase reaction. Asp38 serves as a general acid catalyst during the 'reverse kinase' reaction by donating a proton to the O5' leaving group of the 5'-PO4 strand. The acceptor strand binding mode of CthPnk is distinct from that of bacteriophage T4 Pnk.

Structure and mechanism of the 2',3' phosphatase component of the bacterial Pnkp-Hen1 RNA repair system.

Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from many phyla. Pnkp is composed of three catalytic modules: an N-terminal polynucleotide 5' kinase, a central 2',3' phosphatase and a C-terminal ligase. The phosphatase module is a Mn(2+)-dependent phosphodiesterase-monoesterase that dephosphorylates 2',3'-cyclic phosphate RNA ends. Here we report the crystal structure of the phosphatase domain of Clostridium thermocellum Pnkp with Mn(2+) and citrate in the active site. The protein consists of a core binuclear metallo-phosphoesterase fold (exemplified by bacteriophage λ phosphatase) embellished by distinctive secondary structure elements. The active site contains a single Mn(2+) in an octahedral coordination complex with Asp187, His189, Asp233, two citrate oxygens and a water. The citrate fills the binding site for the scissile phosphate, wherein it is coordinated by Arg237, Asn263 and His264. The citrate invades the site normally occupied by a second metal (engaged by Asp233, Asn263, His323 and His376), and thereby dislocates His376. A continuous tract of positive surface potential flanking the active site suggests an RNA binding site. The structure illuminates a large body of mutational data regarding the metal and substrate specificity of Clostridium thermocellum Pnkp phosphatase.

The adenylyltransferase domain of bacterial Pnkp defines a unique RNA ligase family.

Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from ten different phyla. To gain insight to the mechanism and evolution of this repair system, we determined the crystal structures of the ligase domain of Clostridium thermocellum Pnkp in three functional states along the reaction pathway: apoenzyme, ligase • ATP substrate complex, and covalent ligase-AMP intermediate. The tertiary structure is composed of a classical ligase nucleotidyltransferase module that is embellished by a unique α-helical insert module and a unique C-terminal α-helical module. Structure-guided mutational analysis identified active site residues essential for ligase adenylylation. Pnkp defines a new RNA ligase family with signature structural and functional properties.

Structures of bacterial polynucleotide kinase in a michaelis complex with nucleoside triphosphate (NTP)-Mg2+ and 5'-OH RNA and a mixed substrate-product complex with NTP-Mg2+ and a 5'-phosphorylated oligonucleotide.

Clostridium thermocellum polynucleotide kinase (CthPnk), the 5'-end-healing module of a bacterial RNA repair system, catalyzes reversible phosphoryl transfer from a nucleoside triphosphate (NTP) donor to a 5'-OH polynucleotide acceptor, either DNA or RNA. Here we report the 1.5-Šcrystal structure of CthPnk-D38N in a Michaelis complex with GTP-Mg(2+) and a 5'-OH RNA oligonucleotide. The RNA-binding mode of CthPnk is different from that of the metazoan RNA kinase Clp1. CthPnk makes hydrogen bonds to the ribose 2'-hydroxyls of the 5' terminal nucleoside, via Gln51, and the penultimate nucleoside, via Gln83. The 5'-terminal nucleobase is sandwiched by Gln51 and Val129. Mutating Gln51 or Val129 to alanine reduced kinase specific activity 3-fold. Ser37 and Thr80 donate functionally redundant hydrogen bonds to the terminal phosphodiester; a S37A-T80A double mutation reduced kinase activity 50-fold. Crystallization of catalytically active CthPnk with GTP-Mg(2+) and a 5'-OH DNA yielded a mixed substrate-product complex with GTP-Mg(2+) and 5'-PO4 DNA, wherein the product 5' phosphate group is displaced by the NTP γ phosphate and the local architecture of the acceptor site is perturbed.

Structure and mechanism of the polynucleotide kinase component of the bacterial Pnkp-Hen1 RNA repair system.

Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from many phyla. Pnkp is composed of three catalytic modules: an N-terminal polynucleotide 5'-kinase, a central 2',3' phosphatase, and a C-terminal ligase. Here we report the crystal structure of the kinase domain of Clostridium thermocellum Pnkp bound to ATP•Mg²âº (substrate complex) and ADP•Mg²âº (product complex). The protein consists of a core P-loop phosphotransferase fold embellished by a distinctive homodimerization module composed of secondary structure elements derived from the N and C termini of the kinase domain. ATP is bound within a crescent-shaped groove formed by the P-loop (¹5GSSGSGKST²³) and an overlying helix-loop-helix "lid." The α and ß phosphates are engaged by a network of hydrogen bonds from Thr23 and the P-loop main-chain amides; the γ phosphate is anchored by the lid residues Arg120 and Arg123. The P-loop lysine (Lys21) and the catalytic Mg²âº bridge the ATP ß and γ phosphates. The P-loop serine (Ser22) is the sole enzymic constituent of the octahedral metal coordination complex. Structure-guided mutational analysis underscored the essential contributions of Lys21 and Ser22 in the ATP donor site and Asp38 and Arg41 in the phosphoacceptor site. Our studies suggest a catalytic mechanism whereby Asp38 (as general base) activates the polynucleotide 5'-OH for its nucleophilic attack on the γ phosphorus and Lys21 and Mg²âº stabilize the transition state.

Lactobacillus Plantarum intake mitigates neuropathic pain behavior via enhancing macrophage M2 polarization in a rat model of peripheral neuropathy.

Pro-inflammatory macrophages (M1-polarized) play a crucial role in neuroinflammation and neuropathic pain following nerve injury. Redirecting macrophage polarization toward anti-inflammatory (M2-polarized) phenotypes offers a promising therapeutic strategy. Recognized for their anti-inflammatory and immunomodulatory properties, probiotics are becoming a focal point of research. This study investigated the effects of Lactobacillus plantarum on macrophage polarization, nerve protection, and neuropathic pain behavior following chronic constriction injury (CCI) of the median nerve. Rats received daily oral doses of L. plantarum for 28 days before and 14 days after CCI. Subsequently, behavioral and electrophysiological assessments were performed. The M1 marker CD86 levels, M2 marker CD206 levels, and concentrations of pro-inflammatory and anti-inflammatory cytokines in the injured median nerve were assessed. L. plantarum administration effectively reduced neuropathic pain behavior and the Firmicutes to Bacteroidetes ratio after CCI. Moreover, L. plantarum treatment increased serum short-chain fatty acids (SCFAs) levels, preserved myelination of the injured median nerve, and suppressed injury-induced discharges. In CCI rats treated with L. plantarum, there was a reduction in CD86 and pro-inflammatory cytokine levels, accompanied by an increase in CD206 and the release of anti-inflammatory cytokines. Furthermore, receptors for anti-inflammatory cytokines were localized on Schwann cells, and their expression was significantly upregulated in the injured nerves of CCI rats receiving L. plantarum. In conclusion, L. plantarum shifts macrophage phenotypes from M1 to M2 by promoting the production of SCFAs and enhancing the release of anti-inflammatory cytokines. Ultimately, this process preserves nerve fiber integrity and impedes the onset of neuropathic pain.

Structural and biochemical analysis of the phosphate donor specificity of the polynucleotide kinase component of the bacterial pnkp•hen1 RNA repair system.

Clostridium thermocellum Pnkp is the end-healing and end-sealing subunit of a bacterial RNA repair system. CthPnkp is composed of three catalytic modules: an N-terminal 5'-OH polynucleotide kinase, a central 2',3' phosphatase, and a C-terminal ligase. The crystal structure of the kinase domain bound to ATP•Mg(2+) revealed a rich network of ionic and hydrogen-bonding contacts to the α, ß, and γ phosphates. By contrast, there are no enzymic contacts to the ribose and none with the adenine base other than a π-cation interaction with Arg116. Here we report that the enzyme uses ATP, GTP, CTP, UTP, or dATP as a phosphate donor for the 5'-OH kinase reaction. The enzyme also catalyzes the reverse reaction, in which a polynucleotide 5'-PO4 group is transferred to ADP, GDP, CDP, UDP, or dADP to form the corresponding NTP. We report new crystal structures of the kinase in complexes with GTP, CTP, UTP, and dATP in which the respective nucleobases are stacked on Arg116 but make no other enzymic contacts. Mutating Arg116 to alanine elicits a 10-fold increase in Km for ATP but has little effect on kcat. These findings illuminate the basis for nonspecific donor nucleotide utilization by a P-loop phosphotransferase.

Is Circulating Vitamin D Status Associated with the Risk of Venous Thromboembolism? A Meta-Analysis of Observational Studies.

BACKGROUND: Although vitamin D is antithrombotic, associations between serum vitamin D status and the risk of venous thromboembolism (VTE) remain inconsistent. METHODS: We searched the EMBASE, MEDLINE, Cochrane Library, and Google Scholar databases from inception to June 2022 to identify observational studies examining associations between vitamin D status and VTE risk in adults. The primary outcome presented as odds ratio (OR) or hazard ratio (HR) was the association of vitamin D levels with the risk of VTE. Secondary outcomes included the impacts of vitamin D status (i.e., deficiency or insufficiency), study design, and the presence of neurological diseases on the associations. RESULTS: Pooled evidence from a meta-analysis of sixteen observational studies, including 47648 individuals published from 2013 to 2021, revealed a negative relationship between vitamin D levels and the risk of VTE either based on OR (1.74, 95% confidence interval (CI): 1.37 to 2.20, p < 0.00001; I2 = 31%, 14 studies, 16074 individuals) or HR (1.25, 95% CI: 1.07 to 1.46, p = 0.006; I2 = 0%, 3 studies, 37,564 individuals). This association remained significant in subgroup analyses of the study design and in the presence of neurological diseases. Compared to individuals with normal vitamin D status, an increased risk of VTE was noted in those with vitamin D deficiency (OR = 2.03, 95% CI: 1.33 to 3.11) but not with vitamin D insufficiency. CONCLUSIONS: This meta-analysis demonstrated a negative association between serum vitamin D status and the risk of VTE. Further studies are required to investigate the potential beneficial effect of vitamin D supplementation on the long-term risk of VTE.

Effect of patient decision aids on choice between sugammadex and neostigmine in surgeries under general anesthesia: a multicenter randomized controlled trial.

BACKGROUND: Shared decision making using patient decision aids (PtDAs) was established over a decade ago, but few studies have evaluated its efficacy in Asian countries. We therefore evaluated the application of PtDAs in a decision conflict between two muscle relaxant reversal agents, neostigmine and sugammadex, and sequentially analyzed the regional differences and operating room turnover rates. METHODS: This multicenter, outcome-assessor-blind, randomized controlled trial included 3,132 surgical patients from two medical centers admitted between March 2020 and August 2020. The patients were randomly divided into the classical and PtDA groups for pre-anesthesia consultations. Their clinicodemographic characteristics were analyzed to identify variables influencing the choice of reversal agent. On the day of the pre-anesthesia consultation, the patients completed the four SURE scale (sure of myself, understand information, risk-benefit ratio, encouragement) screening items. The operating turnover rates were also evaluated using anesthesia records. RESULTS: Compared with the classical group, the PtDA group felt more confident about receiving sufficient medical information (P < 0.001), felt better informed about the advantages and disadvantages of the medications (P < 0.001), exhibited a superior understanding of the benefits and risks of their options (P < 0.001), and felt surer about their choice (P < 0.001). Moreover, the PtDA group had a significantly greater tendency to choose sugammadex over neostigmine (P < 0.001). CONCLUSIONS: PtDA interventions in pre-anesthesia consultations provided surgical patients with clear knowledge and better support. PtDAs should be made available in other medical fields to enhance shared clinical decision-making.

GMI, a fungal immunomodulatory protein, ameliorates SARS-CoV-2 envelope protein-induced inflammation in macrophages via inhibition of MAPK pathway.

Clinically, COVID-19 is often accompanied by a severe immune response (cytokine storm) which produces a large number of cytokines, such as TNF-α, IL-6 and IL-12, and consequently causes acute respiratory distress syndrome (ARDS). GMI is a type of fungal immunomodulatory protein that is cloned from Ganoderma microsporum and acts as modulating immunocyte for various inflammatory diseases. This study identifies GMI as a potential anti-inflammatory agent and determines the effects of GMI on the inhibition of SARS-CoV-2-induced cytokine secretion. Functional studies showed that SARS-CoV-2 envelope (E) protein induces inflammatory process in murine macrophages RAW264.7 and MH-S cells and in phorbol 12-myristate 13-acetate (PMA)-stimulated human THP-1 cells. GMI exhibits a strong inhibitory effect for SARS-CoV-2-E-induced pro-inflammatory mediators, including NO, TNF-α, IL-6, and IL-12 in macrophages. GMI reduces SARS-CoV-2-E-induced intracellular inflammatory molecules, such as iNOS and COX-2, and inhibits SARS-CoV-2-E-stimulated phosphorylation of ERK1/2 and P38. GMI also downregulates pro-inflammatory cytokine levels in lung tissue and serum after the mice inhale SARS-CoV-2-E protein. In conclusion, this study shows that GMI acts as an agent to alleviate SARS-CoV-2-E-induced inflammation.

Mutational analysis of the 5'-OH oligonucleotide phosphate acceptor site of T4 polynucleotide kinase.

T4 polynucleotide kinase/phosphatase (Pnkp) exemplifies a family of bifunctional enzymes with 5'-kinase and 3'-phosphatase activities that function in nucleic acid repair. The N-terminal kinase domain belongs to the P-loop phosphotransferase superfamily. The kinase is distinguished by a tunnel-like active site with separate entrances on opposite sides of the protein for the NTP phosphate donor and a 5'-OH single-stranded oligonucleotide phosphate acceptor. Here, we probed by mutagenesis the roles of individual amino acids that comprise the acceptor binding site. We thereby identified Glu57 as an important residue, by virtue of its participation in a salt bridge network with two catalytic residues identified previously: Arg38, which binds the 3'-phosphate of the terminal 5'-OH nucleotide, and the putative general base Asp35 that contacts the nucleophilic 5'-OH group. The 5'-OH nucleoside fits into a pocket lined by aliphatic amino acids (Val131, Pro132 and Val135) that make van der Waals contacts to the nucleobase. Whereas subtraction of these contacts by single alanine substitutions for Val131 or Val135 and glycine for Pro132 had modest effects on kinase activity, the introduction of bulkier phenylalanines for Val131 and Val135 were deleterious, especially V131F, which severely impeded both substrate binding (increasing K(m) by 15-fold) and catalysis (decreasing k(cat) by 300-fold).

Association of Prognostic Nutritional Index with Severity and Mortality of Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

The associations of prognostic nutritional index (PNI) with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19) remain unclear. Electronic databases, including MEDLINE, EMBASE, Google scholar, and Cochrane Library, were searched from inception to 10 May 2022. The associations of PNI with risk of mortality (primary outcome) and disease severity (secondary outcome) were investigated. Merged results from meta-analysis of 13 retrospective studies (4204 patients) published between 2020 and 2022 revealed a lower PNI among patients in the mortality group [mean difference (MD): −8.65, p < 0.001] or severity group (MD: −5.19, p < 0.001) compared to those in the non-mortality or non-severity groups. A per-point increase in PNI was associated with a reduced risk of mortality [odds ratio (OR) = 0.84, 95% CI: 0.79 to 0.9, p < 0.001, I2 = 67.3%, seven studies] and disease severity (OR = 0.84, 95% CI: 0.77 to 0.92, p < 0.001, I2 = 83%, five studies). The pooled diagnostic analysis of mortality yielded a sensitivity of 0.76, specificity of 0.71, and area under curve (AUC) of 0.79. Regarding the prediction of disease severity, the sensitivity, specificity, and AUC were 0.8, 0.61, and 0.65, respectively. In conclusion, this study demonstrated a negative association between PNI and prognosis of COVID-19. Further large-scale trials are warranted to support our findings.

Association of preoperative vitamin D deficiency with the risk of postoperative delirium and cognitive dysfunction: A meta-analysis.

STUDY OBJECTIVE: Despite vitamin D deficiency (VDD) associated with cognitive dysfunction in the general population, the impacts of preoperative VDD on postoperative delirium (POD) and cognitive dysfunction (POCD) remain to be clarified. DESIGN: Meta-analysis of cohort studies. SETTING: Postoperative care. INTERVENTION: Preoperative VDD as the prognostic factor. PATIENTS: Adult patients undergoing surgery. MEASUREMENTS: Databases including MEDLINE, EMBASE, Google scholar, and the Cochrane Library databases were searched from inception to September 2021. Random-effects modeling was applied to the pooling of results on the association between preoperative VDD and POD/POCD. The primary outcome was the association of VDD with the risk of POD/POCD, while the secondary outcomes included other prognostic factors (e.g., hypertension) with the risk of POD/POCD. A prediction interval (PI) was calculated to indicate the range of a true effect size of a future study in 95% of all populations. MAIN RESULTS: Meta-analysis of seven observational studies involving 2673 patients showed that the pooled incidence of POD/POCD was 29% (95% confidence interval (CI): 18% to 44%). Our results demonstrated that preoperative VDD increased the risk of POD/POCD [odds ratio (OR) = 1.54, 95% CI: 1.21-1.97, p < 0.01; I2 = 29.2%, seven studies, 2673 patients; 95% PI: 0.89-2.67], while vitamin D insufficiency was not associated with a higher risk of POD/POCD (OR = 0.88, 95% CI: 0.49-1.57, p = 0.66; I2 = 62.6%, four studies, 1410 patients; 95% PI: 0.09-8.79). The PI in our primary outcome (i.e., 0.89 to 2.67) containing 1.0 suggested the possibility of inconsistent results in future studies. Patients with POD/POCD were older compared to those without. Hypertension, diabetes mellitus, male gender, or smoking was not recognized as risk factors for POD/POCD. CONCLUSIONS: Our results demonstrated that preoperative vitamin D deficiency was associated with postoperative cognitive impairment. Given the prediction interval, more future studies are needed to elucidate associations between VDD and POD/POCD.