A retrospective observational study evaluating the association between vasoactive-inotropic score and mortality after major abdominal surgery.

The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0-5, > 5-15, > 15-30, > 30-45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16-12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09-6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64-0.75) and 0.67 (95% CI 0.62-0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.

Identifying vital nodes for yeast network by dynamic network entropy.

BACKGROUND: The progress of the cell cycle of yeast involves the regulatory relationships between genes and the interactions proteins. However, it is still obscure which type of protein plays a decisive role in regulation and how to identify the vital nodes in the regulatory network. To elucidate the sensitive node or gene in the progression of yeast, here, we select 8 crucial regulatory factors from the yeast cell cycle to decipher a specific network and propose a simple mixed K2 algorithm to identify effectively the sensitive nodes and genes in the evolution of yeast. RESULTS: Considering the multivariate of cell cycle data, we first utilize the K2 algorithm limited to the stationary interval for the time series segmentation to measure the scores for refining the specific network. After that, we employ the network entropy to effectively screen the obtained specific network, and simulate the gene expression data by a normal distribution approximation and the screened specific network by the partial least squares method. We can conclude that the robustness of the specific network screened by network entropy is better than that of the specific network with the determined relationship by comparing the obtained specific network with the determined relationship. Finally, we can determine that the node CDH1 has the highest score in the specific network through a sensitivity score calculated by network entropy implying the gene CDH1 is the most sensitive regulatory factor. CONCLUSIONS: It is clearly of great potential value to reconstruct and visualize gene regulatory networks according to gene databases for life activities. Here, we present an available algorithm to achieve the network reconstruction by measuring the network entropy and identifying the vital nodes in the specific nodes. The results indicate that inhibiting or enhancing the expression of CDH1 can maximize the inhibition or enhancement of the yeast cell cycle. Although our algorithm is simple, it is also the first step in deciphering the profound mystery of gene regulation.

Identifying therapeutic targets for breast cancer: insights from systematic Mendelian randomization analysis.

Background: Breast cancer (BC) exhibits a high incidence rate, imposing a substantial burden on healthcare systems. Novel drug targets are urgently needed for BC. Mendelian randomization (MR) has gained widespread application for identifying fresh therapeutic targets. Our endeavor was to pinpoint circulatory proteins causally linked to BC risk and proffer potential treatment targets for BC. Methods: Through amalgamating protein quantitative trait loci from 2,004 circulating proteins and comprehensive genome-wide association study data from the Breast Cancer Association Consortium, we conducted MR analyses. Employing Steiger filtering, bidirectional MR, Bayesian colocalization, phenotype scanning, and replication analyses, we further solidified MR study outcomes. Additionally, protein-protein interaction (PPI) network was harnessed to unveil latent associations between proteins and prevailing breast cancer medications. The phenome-wide MR (Phe-MR) was employed to assess potential side effects and indications for the druggable proteins of BC. Finally, we further affirmed the drugability of potential drug targets through mRNA expression analysis and molecular docking. Results: Through comprehensive analysis, we identified five potential drug targets, comprising four (TLR1, A4GALT, SNUPN, and CTSF) for BC and one (TLR1) for BC_estrogen receptor positive. None of these five potential drug targets displayed reverse causation. Bayesian colocalization suggested that these five latent drug targets shared variability with breast cancer. All drug targets were replicated within the deCODE cohort. TLR1 exhibited PPI with current breast cancer therapeutic targets. Furthermore, Phe-MR unveiled certain adverse effects solely for TLR1 and SNUPN. Conclusion: Our study uncovers five prospective drug targets for BC and its subtypes, warranting further clinical exploration.

Effects of intravenous lidocaine on postoperative pain and gastrointestinal function recovery following gastrointestinal surgery: a meta-analysis.

INTRODUCTION: The full extent of intravenous lidocaine's effectiveness in alleviating postoperative pain and enhancing gastrointestinal function recovery remains uncertain. EVIDENCE ACQUISITION: We conducted an exhaustive search of databases to identify randomized controlled trials that compared intravenous lidocaine infusion's efficacy to that of a placebo or routine care in patients undergoing gastrointestinal surgery. The primary outcome measure was resting pain scores 24 h postoperatively. We utilized a random-effects model based on the intention-to-treat principle for the overall results. EVIDENCE SYNTHESIS: This study included twenty-four trials with 1533 patients. Intravenous lidocaine significantly reduced resting pain scores 24 h after gastrointestinal surgery (twenty trials, SMD -0.67, 95% CI -1.09 to -0.24, P=0.002, I2 = 90%). This finding was consistent in subgroup analyses and sensitivity analyses. The benefit was also observed at other resting and moving time points (1, 2, 4, and 12 h) postoperatively. Intravenous lidocaine significantly decreased opioid consumption within 24 h after surgery (eleven trials, SMD: -1.19; 95% CI: -1.99 to -0.39; P=0.003). Intravenous lidocaine also shortened the time to bowel sound (MD: -8.51; 95% CI: -14.59 to -2.44; P=0.006), time to first flatus (MD: -6.00; 95% CI: -9.87 to -2.13; P=0.002), and time to first defecation (MD: -9.77; 95% CI: -17.19 to -2.36; P=0.01). CONCLUSIONS: Perioperative intravenous lidocaine can alleviate acute pain and expedite gastrointestinal function recovery in patients undergoing gastrointestinal surgery. However, the results should be interpreted with caution due to substantial heterogeneity. Further large-scale studies are necessary to validate these findings.

TXNIP knockdown protects rats against bupivacaine-induced spinal neurotoxicity via the inhibition of oxidative stress and apoptosis.

Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity.

Cytosolic mtDNA-cGAS-STING axis contributes to sepsis-induced acute kidney injury via activating the NLRP3 inflammasome.

BACKGROUND: NLRP3 inflammasome activation is significantly associated with sepsis-induced acute kidney injury (S-AKI). Cytosolic DNA derived from damaged mitochondria has been reported to activate NLRP3 inflammasome via upregulating the cyclic GMP-AMP synthase (cGAS)-the stimulator of interferon genes (STING) axis in nucleus pulposus cell and cardiomyocytes. However, the regulatory effect of mitochondria DNA (mtDNA)-cGAS-STING axis on the NLRP3 inflammasome in S-AKI remains unclear. METHODS: In the current study, we established an in vivo model of S-AKI by intraperitoneally injecting male C57BL/6 J mice with lipopolysaccharide (LPS). Next, selective cGAS inhibitor RU.521, and STING agonist DMXAA were intraperitoneally injected in the mice; then, blood urea nitrogen (BUN), serum creatinine (CRE), urinary kidney injury molecular-1 (KIM-1), pathological changes, and infiltrated neutrophils were detected to assess kidney injury. We also performed western blot and immunofluorescence assays to evaluate STING, cGAS, TBK-1, p-TBK-1, IRF3, p-IRF3, NF-kB, p-NF-kB, NLRP3, cleaved caspase-1, caspase-1, GSDMD-N, and GSDMD expression levels in kidney tissues. IL-18 and IL-1ß in renal tissue were identified by ELISA. In vitro, we treated HK-2 cells with LPS to establish a cell model of S-AKI. Furthermore, ethidium bromide (EtBr) was administered to deplete mitochondria DNA (mtDNA). LPS-induced cytotoxicity was evaluated by LDH release assay. Protein expression of cGAS, STING, and NLRP3 in was quantified by western blot. Cytosolic mtDNA was detected by immunofluorescence and q-PCR. Released IL-1ß and IL-18 in HK-2 supernatants were detected by ELISA. RESULTS: LPS injection induced S-AKI in mice, as evidenced by neutrophil infiltration, tubular vacuolation, and increased levels of serum creatinine (CRE), blood urea nitrogen (BUN), and urinary KIM-1. In addition, LPS activated the cGAS-STING axis and NLRP3 inflammasome in vivo, illustrated by increased phosphorylation levels of TBK-1, IRF3, and NF-kB protein, increased ratio of cleaved caspase-1 to caspase-1 and GSDMD-N to GSDMD, and increased IL-1ß and IL-18 levels. Moreover, the cGAS inhibitor RU.521 effectively attenuated NLRP3 inflammasome and S-AKI; however, these effects were abolished by treatment with the STING agonist DMXAA. Furthermore, cytosolic release of mtDNA and activation of the cGAS-STING-NLRP3 axis were observed in LPS-treated HK-2 cells. Inhibiting mtDNA replication by Ethidium Bromide (EtBr) treatment reduced cytosolic mtDNA accumulation and downregulated the cGAS-STING-NLRP3 axis, ameliorating the cytotoxicity induced by LPS. CONCLUSION: This study demonstrated that the cGAS-STING axis was triggered by cytosolic mtDNA and participated in the development of S-AKI by activating NLRP3 inflammasome. Reducing cytosolic mtDNA accumulation or inhibiting the cGAS-STING axis may be potential therapeutic targets for S-AKI.

Comparing safety and efficacy: MemoLefort versus watchman for left atrial appendage closure.

BACKGROUND: The MemoLefort is a new plug occluder for left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF). This study compares the safety and efficacy of MemoLefort and the well-established Watchman occluder for LAAC. METHODS: Between January 2021 and September 2022, a cohort of 189 consecutive patients who underwent LAAC with MemoLefort or Watchman at The Second Affiliated Hospital of Wenzhou Medical University were included. Patients with MemoLefort or Watchman devices were compared in terms of the primary safety endpoints encompassing major periprocedural complications and major bleeding events at follow-up, the primary efficacy endpoint of all-cause stroke, systemic embolism and cardiovascular/unexplained death, and the combined hazard endpoint, a composite of all the above-mentioned hazards. RESULTS: Of the MemoLefort group (n = 83) and Watchman group (n = 106), the mean age, CHA2DS2-VASc score, and HAS-BLED score were 67.6 ± 9.2 vs. 69.0 ± 10.6 years, 3.9 ± 1.9 vs. 3.8 ± 1.9, and 1.6 ± 1.0 vs. 1.7 ± 1.2, respectively. After a median follow-up duration of 198 (99-329) vs. 334 (171-497) days, the primary endpoints of efficacy [2/49, 4.1% (MemoLefort) vs. 2/97, 2.1% (Watchman); hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.20-11.08; P = 0.68] and safety (1/49, 2.0% vs. 5/97, 5.2%; HR, 0.26; 95% CI, 0.05-1.31; P = 0.19), as well as the combined hazard endpoint (3/49, 61% vs. 6/97, 6.2%; HR, 0.70; 95% CI, 0.18-2.58; P = 0.59) were similar between groups. CONCLUSIONS: In the short term, LAAC with MemoLefort provided similar efficacy, safety, and net clinical benefit in comparison to Watchman devices.

Resveratrol­mediated activation of SIRT1 inhibits the PERK­eIF2α­ATF4 pathway and mitigates bupivacaine­induced neurotoxicity in PC12 cells.

Endoplasmic reticulum (ER) stress and apoptosis play significant roles in the development of neurotoxicity caused by bupivacaine (BUP). By activating sirtuin 1 (SIRT1), resveratrol (RSV) can regulate various cellular processes associated with anti-oxidative stress, anti-apoptosis and anti-inflammatory responses, thereby exerting neuroprotective effects. However, it remains unknown whether the activation of SIRT1 by RSV is able to attenuate BUP-induced ER stress and apoptosis. Therefore, the present study aimed to explore the effect of RSV on BUP-induced cytotoxicity in PC12 cells and the underlying mechanism. Cell Counting Kit-8 assays, flow cytometry and inverted phase-contrast microscopy were used to assess the viability, apoptosis rate and morphological changes of the cells, respectively. Western blotting and immunofluorescence staining were used to analyze the levels of SIRT1, the apoptosis-related proteins Bax, Bcl-2 and cleaved caspase-3, the ER stress-related proteins glucose-regulated protein 78, caspase-12 and CHOP, and the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2 α (eIF2α)-activating transcription factor 4 (ATF4) pathway-associated proteins phosphorylated (p)-PERK, PERK, p-eIF2α, eIF2α and ATF4. The results revealed that BUP induced cell apoptosis and decreased cell viability, accompanied by the downregulation of SIRT1. However, RSV restored SIRT1 protein expression, downregulated the expression of the pro-apoptotic protein Bax, upregulated the expression of the anti-apoptotic protein Bcl-2, decreased the apoptosis rate of the cells and increased cell viability. Furthermore, the anti-apoptotic effects exhibited by RSV were associated with inhibition of the PERK-eIF2α-ATF4 pathway of ER stress. However, the protective effect of RSV was significantly mitigated by the SIRT1 inhibitor EX527. These results indicate that the activation of SIRT1 by RSV alleviates BUP-induced PC12 cell ER stress and apoptosis via regulation of the PERK-eIF2α-ATF4 pathway. These findings offer insights into the molecular mechanism underlying BUP-induced apoptosis and suggest the potential of RSV as a therapeutic agent against the neurotoxicity caused by BUP.

Perioperative intravenous lidocaine for postoperative pain in patients undergoing breast surgery: a meta-analysis with trial sequential analysis of randomized controlled trials.

Background: The effectiveness of intravenous lidocaine infusion in managing acute and chronic pain following breast surgery has been a topic of debate. This meta-analysis aims to assess the impact of perioperative intravenous lidocaine on the relief of postoperative pain among patients undergoing breast surgery. Methods: A systematic search of databases was conducted to identify randomized controlled trials (RCTs) that compared the effects of intravenous lidocaine infusion with placebo or routine care in patients undergoing breast surgery. The primary outcome of interest was the occurrence of chronic post-surgical pain (CPSP) at the longest follow-up. Meta-analyses, incorporating trial sequential analysis, were performed using a random-effects model to assess the overall effect. Results: A total of twelve trials, involving 879 patients, were included in the analysis. Perioperative intravenous lidocaine demonstrated a significant reduction in the incidence of CPSP at the longest follow-up (risk ratio [RR] 0.62, 95% confidence interval [CI] 0.48-0.81; P = 0.0005; I2 = 6%). Trial sequential analysis (TSA) indicated that the cumulative z curve crossed the trial sequential monitoring boundary for benefit, providing sufficient and conclusive evidence. Furthermore, intravenous lidocaine was associated with decreased opioid consumption and a shorter length of hospital stay. Conclusion: Perioperative intravenous lidocaine is effective in relieving acute and CPSP in patients undergoing breast surgery. Systematic review registration: https://inplasy.com/, identifier INPLASY2022100033.

[Retracted] MicroRNA­132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the flow cytometric data shown in Fig. 2D on p. 1675 had already been submitted in different form in the following paper written by different authors at different research institutes: Tian R, Li Y and Gao M: Shikonin causes cell­cycle arrest and induces apoptosis by regulating the EGFR­NF­κB signalling pathway in human epidermoid carcinoma A431 cells. Biosci Rep 28: e00189, 2015. After having conducted an independent review of the data in this figure in the Editorial Office, the concerns of the reader were found to be validated. Therefore, since the contentious data in the above article had already been submitted for publication prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 47: 1672­1684, 2015; DOI: 10.3892/ijo.2015.3147].

Ferrostatin-1 ameliorates Bupivacaine-Induced spinal neurotoxicity in rats by inhibiting ferroptosis.

Bupivacaine (BUP) has previously been shown to trigger neurotoxicity after spinal anesthesia. Further, ferroptosis has been implicated in the pathological processes associated with various central nervous system diseases. Although the impact of ferroptosis on BUP-induced neurotoxicity in the spinal cord has not been fully understood, this research aims to investigate this relationship in rats. Additionally, this study aims to determine whether ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, can provide protection against BUP-induced spinal neurotoxicity. The experimental model for BUP-induced spinal neurotoxicity involved the administration of 5% bupivacaine through intrathecal injection. Then, the rats were randomized into the Control, BUP, BUP + Fer-1, and Fer-1 groups. BBB scores, %MPE of TFL, and H&E and Nissl stainings showed that intrathecal Fer-1 administration improved functional recovery, histological outcomes, and neural survival in BUP-treated rats. Moreover, Fer-1 has been found to alleviate the BUP-induced alterations related to ferroptosis, such as mitochondrial shrinkage and disruption of cristae, while also reducing the levels of malondialdehyde (MDA), iron, and 4-hydroxynonenal (4HNE). Fer-1 also inhibits the accumulation of reactive oxygen species (ROS) and restores the normal levels of glutathione peroxidase 4 (GPX4), cystine/glutamate transporter (xCT), and glutathione (GSH). Furthermore, double-immunofluorescence staining revealed that GPX4 is primarily localized in the neurons instead of microglia or astroglia in the spinal cord. In summary, we demonstrated that ferroptosis play a pivotal role in mediating BUP-induced spinal neurotoxicity, and Fer-1 ameliorated BUP-induced spinal neurotoxicity by reversing the underlying ferroptosis-related changes in rats.

Resveratrol Suppresses Bupivacaine-Induced Spinal Neurotoxicity in Rats by Inhibiting Endoplasmic Reticulum Stress via SIRT1 Modulation.

Bupivacaine (BUP) may cause neurotoxic effects after spinal anesthesia. Resveratrol (RSV), a natural agonist of Silent information regulator 1 (SIRT1), protects various tissues and organs from damage by regulating endoplasmic reticulum (ER) stress. The aim of this study is to explore whether RSV could alleviate the neurotoxicity induced by bupivacaine via regulating ER stress. We established a model of bupivacaine-induced spinal neurotoxicity in rats using intrathecal injection of 5% bupivacaine. The protective effect of RSV was evaluated by injecting intrathecally with 30 µg/µL RSV in total of 10 µL per day for 4 consecutive days. On day 3 after bupivacaine administration, tail-flick latency (TFL) tests and the Basso, Beattie, and Bresnahan (BBB) locomotor scores were assessed to neurological function, and the lumbar enlargement of the spinal cord was obtained. H&E and Nissl staining were used to evaluate the histomorphological changes and the number of survival neurons. TUNEL staining was conducted to determine apoptotic cells. The expression of proteins was detected by IHC, immunofluorescence, and western blot. The mRNA level of SIRT1 was determined by RT-PCR. Bupivacaine caused spinal cord neurotoxicity by inducing cell apoptosis and triggering ER stress. RSV treatment promoted the recovery of neurological dysfunction after bupivacaine administration by suppressing neuronal apoptosis and ER stress. Furthermore, RSV upregulated SIRT1 expression and inhibited PERK signaling pathway activation. In summary, resveratrol suppresses bupivacaine-induced spinal neurotoxicity in rats by inhibiting endoplasmic reticulum stress via SIRT1 modulation.

Prognostic value of elevated plasma angiotensin-converting enzyme 2 in cardiometabolic diseases: A review.

Angiotensin-converting enzyme 2, as an internal anti regulator of the renin-angiotensin hormone cascade reaction, plays a protective role in vasodilation, inhibition of fibrosis, and initiation of anti-inflammatory and antioxidative stress by degrading angiotensin II and generating angiotensin (1-7). Multiple studies have shown that plasma angiotensin-converting enzyme 2 activity is low in healthy populations without significant cardiometabolic disease, and elevated plasma angiotensin-converting enzyme 2 levels can be used as a novel biomarker of abnormal myocardial structure and/or adverse events in cardiometabolic diseases. This article aims to elaborate the determinants of plasma angiotensin-converting enzyme 2 concentration, the relevance between angiotensin-converting enzyme 2 and cardiometabolic disease risk markers, and its relative importance compared with known cardiovascular disease risk factors. Confronted with the known cardiovascular risk factors, plasma angiotensin-converting enzyme 2 (ACE2) concentration uniformly emerged as a firm predictor of abnormal myocardial structure and/or adverse events in cardiometabolic diseases and may improve the risk prediction of cardiometabolic diseases when combined with other conventional risk factors. Cardiovascular disease is the leading cause of death worldwide, while the renin-angiotensin system is the main hormone cascade system involved in the pathophysiology of cardiovascular disease. A multi-ancestry global cohort study from the general population by Narula et al revealed that plasma ACE2 concentration was strongly associated with cardiometabolic disease and might be an easily measurable indicator of renin-angiotensin system disorder. The association between this atypical hormone disorder marker and cardiometabolic disease is isolated from conventional cardiac risk factors and brain natriuretic peptide, suggesting that a clearer comprehending of the changes in plasma ACE2 concentration and activity may help us to improve the risk prediction of cardiometabolic disease, guide early diagnosis and feasible therapies, and develop and test new therapeutic targets.

The association between mortality and door-to-antibiotic time: a systematic review and meta-analysis.

PURPOSE: Previous studies evaluating the impact of antibiotic timing on mortality in sepsis have shown conflicting results. We performed a meta-analysis to evaluate the association between door-to-antibiotic time (each hour of delay) and mortality in sepsis. METHODS: We searched PubMed and Embase through 10 November 2022 to identity cohort studies that evaluated the adjusted association between door-to-antibiotic time (each hour of delay) and mortality in adult patients with sepsis. The primary outcome was mortality. Analysis was based on inverse-variance weighting using a fixed-effects model. The variances were derived from the logarithms of the reported confidence intervals (CIs) for associations. We estimated the odds ratio, 95% CI, and number needed to treat for the pooled data. RESULTS: Fifteen cohort studies involving 106 845 patients were included in the meta-analysis. Door-to-antibiotic time (each hour of delay) was associated with increased risk of mortality (odds ratio: 1.07; 95% CI: 1.06-1.08; P < 0.0001; number needed to treat = 91), with high heterogeneity (I2 = 82.2%). The association was robust in sensitivity analyses and consistent in subgroup analyses. No publication bias was found. CONCLUSION: In adult patients with sepsis, each hour of delay in antibiotic administration is associated with increased odds of mortality. Key messages What is already known on this topic Sepsis is a common and lethal syndrome that affects millions of people worldwide. The updated 2018 Surviving Sepsis Campaign guidelines recommended initiating empirical broad-spectrum antibiotic coverage within 1 hour of identification of sepsis and septic shock. Delay in antibiotic administration may increase the risk of mortality in patients with sepsis. What this study adds This meta-analysis evaluates and quantifies the association between door-to-antibiotic time (each hour of delay) and mortality in patients with sepsis. Each hour of delay in antibiotic administration is associated with increased odds of mortality in sepsis. The number needed to treat (NNT) with delayed antibiotic administration for one additional death was 91. How this study might affect research, practice, or policy: More efforts should be made to speed up the diagnosis of sepsis or sepsis shock.

Subtask analysis of process data through a predictive model.

Response process data collected from human-computer interactive items contain detailed information about respondents' behavioural patterns and cognitive processes. Such data are valuable sources for analysing respondents' problem-solving strategies. However, the irregular data format and the complex structure make standard statistical tools difficult to apply. This article develops a computationally efficient method for exploratory analysis of such process data. The new approach segments a lengthy individual process into a sequence of short subprocesses to achieve complexity reduction, easy clustering and meaningful interpretation. Each subprocess is considered a subtask. The segmentation is based on sequential action predictability using a parsimonious predictive model combined with the Shannon entropy. Simulation studies are conducted to assess the performance of the new method. We use a case study of PIAAC 2012 to demonstrate how exploratory analysis for process data can be carried out with the new approach.

Accurate Assessment via Process Data.

Accurate assessment of a student's ability is the key task of a test. Assessments based on final responses are the standard. As the infrastructure advances, substantially more information is observed. One of such instances is the process data that is collected by computer-based interactive items and contain a student's detailed interactive processes. In this paper, we show both theoretically and with simulated and empirical data that appropriately including such information in the assessment will substantially improve relevant assessment precision.

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial.

This current phase II clinical trial was to compare the effect and safety of adamgammadex, a new cyclodextrin-based selective relaxant binding agent, with sugammadex to reverse rocuronium-induced neuromuscular block. Patients were randomised to receive adamgammadex (4 or 6 mg kg-1) or sugammadex (2 mg kg-1, as a positive control group) at the reappearance of the second twitch (T2) in response to TOF stimulation. The standard safety data were collected. The 4 mg kg-1 (n = 16) and 6 mg kg-1 (n = 20) adamgammadex- and 2 mg kg-1 (n = 20) sugammadex-induced recovery time of TOF ratio to 0.9 were 2.3, 1.6, and 1.5 min, respectively (p = 0.49). The 4 mg kg -1 adamgammadex-induced median recovery time was longer than that of 2 mg kg-1 sugammadex (p = 0.01), and there was no difference between the 6 mg kg -1 adamgammadex group and 2 mg kg-1 sugammadex group (p = 0.32). Then, the number of patients who experienced adverse events (AEs) was 6, 11, and 14 for adamgammadex at 4, 6 mg kg-1 and sugammadex at 2 mg kg-1, respectively. The treatment emergent AEs that occurred more than twice were detailed as follows: incision site pain, hypotension, emesis, fever, throat pain, blood bilirubin increase, abnormal T-wave of ECG, dizziness, incision site swelling, postoperative fever, expectoration, and nausea. For drug-related AEs, the increased urine acetone bodies and first-degree atrioventricular block were observed in two patients from sugammadex group. Then, the previously reported AEs were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block as sugammadex.

Advances in the research of plant-derived natural products against retinoblastoma.

Retinoblastoma (RB) is a highly aggressive ocular tumor, and due to socioeconomic and medical constraints, many children receive treatment only in the metaphase and advanced clinical stages, resulting in high rates of blindness and disability. Although several approaches exist in the treatment of RB, some children with the disease do not have satisfactory results because of various factors. Plant-derived natural products have shown definite therapeutic effects in the treatment of various tumors and are also widely used in the study of RB. We review plant-derived natural products used in the study of anti-RB to provide ideas for the clinical application of these drugs and the development of new therapeutic drugs.

Ultrasound-Guided Posterior Quadratus Lumborum Block for Acute Postoperative Analgesia in Adult Patients: A Meta-Analysis of Randomized Controlled Trials.

Objective: The quadratus lumborum block provides postoperative analgesia for patients undergoing abdominal surgery, although there are three common approaches to perform this block. The present meta-analysis investigated the effectiveness of posterior quadratus lumborum block (QLB2) after surgery. Methods: PubMed, Embase, and the Cochrane Central Register were searched from inception to 26 August 2021 for randomized controlled trials that evaluated the analgesic efficacy of QLB2 vs control (placebo or no block). The primary outcomes were pain scores at 6 h, 12 h, and 24 h after surgery. The secondary outcomes were morphine consumption at 24 h after surgery and the postoperative complications. Results: The present meta-analysis included 14 studies conducted with a total of 1001 patients. In comparison to control group, the QLB2 group presented significantly lower rest pain scores at 6 h (SMD -0.59; 95% CI: -1.05, -0.12; p = 0.01, I2 = 84%; GRADE = moderate), 12 h (SMD: -0.83; 95% CI: -1.47, -0.19; p = 0.01; I2 = 88%; GRADE = low), and 24 h (SMD: -0.37; 95% CI: -0.71, -0.03; p = 0.03; I2 = 80%; GRADE = moderate) after surgery. The dynamic pain scores were significantly reduced, compared to control, in the QLB2 group at 12 h (SMD: -0.93; 95% CI: -1.52, -0.33; p = 0.002; I2 = 83%; GRADE = low) and 24 h (SMD: -0.52; 95% CI: -0.93, -0.11; p = 0.01; I2 = 83%; GRADE = moderate) after surgery. In addition, the QLB2 group presented reduced postoperative opioid consumption at 24 h (SMD: -0.45; 95% CI: -0.86, -0.03; p = 0.03; I2 = 78%; GRADE = moderate). The subgroup analyses revealed that the analgesic benefit of QLB2 did not persist beyond 24 h when the patients were under spinal anesthesia. Conclusion: Ultrasound-guided QLB2 could provide effective analgesia for patients under general anesthesia by decreasing the intensity of pain and opioid requirement when used within 24 h after abdominal surgery.

Ultrasound-guided quadratus lumborum block for postoperative analgesia in renal surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Quadratus lumborum block (QLB) guided by ultrasound is a novel local block anesthesia technique, which can be used in various surgeries for multimodal analgesia. Its analgesic effectiveness for renal surgery is still uncertain. The aim of this meta-analysis was to assess the postoperative analgesic efficacy of QLB in adult patients undergoing renal surgery. METHODS: We systematically searched randomized controlled trials (RCTs) through the databases of Cochrane Library, Embase, and PubMed until June 21, 2021. Postoperative consumption of opioid in the first 24-h was set as the primary outcome. The risk of bias was evaluated by Cochrane methodology. RESULTS: Ten RCTs involving 577 patients were eligible for our inclusion criteria. Ultrasound-guided QLB significantly reduced postoperative consumption of opioid in the first 24 h after surgery (mean differences [MD] - 17.58, 95% confidence interval [CI] - 23.14 to - 12.02, P < 0.00001, I2 = 98%). Similarly, the results were consistent in subgroups analysis of both different types of renal surgeries and different QLB approaches. The QLB also significantly decreased postoperative static pain scores at different time points, and reduced the incidence of postoperative nausea and vomiting (PONV) (risk ratio [RR] = 0.48, 95% CI 0.33 to 0.70, P = 0.0002, I2 = 0%) and the number of rescue analgesia patients (RR = 0.34, 95% CI 0.20 to 0.58, P < 0.0001, I2 = 0%). No major complications related to QLB were reported in the included studies. CONCLUSIONS: Ultrasound-guided QLB improves postoperative analgesic efficacy and reduces PONV in adult patients undergoing renal surgery. There is currently limited evidence concerning the analgesic effects of different QLB approaches after renal surgery, and further research is required in this area. PROSPERO REGISTRATION: PROSPERO Registration CRD42021260821.