Postoperative pain relief after total knee arthroplasty: A Bayesian network meta-analysis and systematic review of analgesic strategies based on nerve blocks.

STUDY OBJECTIVE: A Bayesian network meta-analysis was performed to compare the analgesic efficacy of the following nerve block techniques: femoral nerve block (FNB), adductor canal block (ACB), infiltration between the popliteal artery and the capsule of the posterior knee (iPACK), and genicular nerve block (GNB) following total knee arthroplasty (TKA). DESIGN: Systematic review and network meta-analysis (NMA). PATIENTS AND MEASUREMENTS: We searched the Web of Science, PubMed, EMBASE, and Cochrane Library databases until September 20, 2022. Patients who were treated by any of the above four nerve block techniques (alone or in combination) after TKA were included. Patients who underwent minimally invasive knee surgery were excluded. The indicators included pain scores during rest and mobilization, opioid consumption after surgery, postsurgical mobilization function (ROM [range of motion], TUG [Timed-Up-and-Go] test) at 24 h and 48 h, and length of hospital stay. The risk of bias was assessed by the Cochrane risk of bias tool. RESULTS: Forty-two studies involving 2857 patients were eligible for this study. This NMA suggested that ACB + iPACK was the most efficacious option for improving ambulation ability and shortening the length of hospital stay. Furthermore, ACB + iPACK was the best regimen for resting-pain and movement-pain relief (78% and 87%, respectively) and for reducing opioid consumption (90%) at 48 h. However, FNB + iPACK was the most efficacious option for relief of resting pain (42%) and reducing opioid consumption (68%) at 24 h; GNB was the most efficacious option for movement pain relief at 24 h (94%). CONCLUSION: Considering both pain control and knee functional recovery, ACB + iPACK may be the optimal analgesic regimen for patients after TKA. At the same time, it significantly reduces pain and opioid consumption at 48 h. However, ACB + iPACK is not the recommended technique for short-term (24 h) pain control. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42022362322).

Identification of renal ischemia reperfusion injury-characteristic genes, pathways and immunological micro-environment features through bioinformatics approaches.

BACKGROUND: Biomarkers and pathways associated with renal ischemia reperfusion injury (IRI) had not been well unveiled. This study was intended to investigate and summarize the regulatory networks for related hub genes. Besides, the immunological micro-environment features were evaluated and the correlations between immune cells and hub genes were also explored. METHODS: GSE98622 containing mouse samples with multiple IRI stages and controls was collected from the GEO database. Differentially expressed genes (DEGs) were recognized by the R package limma, and the GO and KEGG analyses were conducted by DAVID. Gene set variation analysis (GSVA) and weighted gene coexpression network analysis (WGCNA) had been implemented to uncover changed pathways and gene modules related to IRI. Besides the known pathways such as apoptosis pathway, metabolic pathway, and cell cycle pathways, some novel pathways were also discovered to be critical in IRI. A series of novel genes associated with IRI was also dug out. An IRI mouse model was constructed to validate the results. RESULTS: The well-known IRI marker genes (Kim1 and Lcn2) and novel hub genes (Hbegf, Serpine2, Apbb1ip, Trip13, Atf3, and Ncaph) had been proved by the quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, miRNAs targeted to the dysregulated genes were predicted and the miRNA-target network was constructed. Furthermore, the immune infiltration for these samples was predicted and the results showed that macrophages infiltrated to the injured kidney to affect the tissue repair or fibrosis. Hub genes were significantly positively or negatively correlated with the macrophage abundance indicating they played a crucial role in macrophage infiltration. CONCLUSIONS: Consequently, the pathways, hub genes, miRNAs, and the immune microenvironment may explain the mechanism of IRI and might be the potential targets for IRI treatments.

Prevention of spinal hypotension during cesarean section: A systematic review and Bayesian network meta-analysis based on ephedrine, phenylephrine, and norepinephrine.

AIM: The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section. METHODS: The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores. RESULTS: About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 µg norepinephrine and 81-120 mg phenylephrine; 121-150 µg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 µg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 µg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 µg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores. CONCLUSIONS: Based on this study, 5-10 mg ephedrine and 13-16 µg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.

miRNA155-5P participated in DDX3X targeted regulation of pyroptosis to attenuate renal ischemia/reperfusion injury.

BACKGROUND: Renal ischemia/reperfusion injury (IRI) induced pathological damage to renal microvessels and tubular epithelial cells through multiple factors. However, studies investigated whether miRNA155-5P targeted DDX3X to attenuate pyroptosis were scarce. RESULTS: The expression of pyroptosis-related proteins (caspase-1, interleukin-1ß (IL-1ß), NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-18) were up-regulated in the IRI group. Additionally, miR-155-5p was higher in the IRI group comparing with the sham group. The DDX3X was inhibited by the miR-155-5p mimic more than in the other groups. DEAD-box Helicase 3 X-Linked (DDX3X), NLRP3, caspase-1, IL-1ß, IL-18, LDH, and pyroptosis rates were higher in all H/R groups than in the control group. These indicators were higher in the miR-155-5p mimic group than in the H/R and the miR-155-5p mimic negative control (NC) group. CONCLUSIONS: Current findings suggested that miR-155-5p decreased the inflammation involved in pyroptosis by downregulating the DDX3X/NLRP3/caspase-1 pathway. METHODS: Using the models of IRI in mouse and the hypoxia-reoxygenation (H/R)-induced injury in human renal proximal tubular epithelial cells (HK-2 cells), we analyzed the changes in renal pathology and the expression of factors correlated with pyroptosis and DDX3X. Real-time reverse transcription polymerase chain reaction (RT-PCR) detected miRNAs and enzyme-linked immunosorbent assay (ELISA) was used to detect lactic dehydrogenase activity. The StarBase and luciferase assays examined the specific interplay of DDX3X and miRNA155-5P. In the IRI group, severe renal tissue damage, swelling, and inflammation were examined.

Role of microRNAs in programmed cell death in renal diseases: A review.

MicroRNAs (miRNAs) regulate gene expression involving kidney morphogenesis and cell proliferation, apoptosis, differentiation, migration, invasion, immune evasion, and extracellular matrix remodeling. Programmed cell death (PCD) is mediated and regulated by specific genes and a wealth of miRNAs, which participate in various pathological processes. Dysregulation of miRNAs can disrupt renal development and induce the onset and progression of various renal diseases. An in-depth understanding of how miRNAs regulate renal development and diseases is indispensable to comprehending how they can be used in new diagnostic and therapeutic approaches. However, the mechanisms are still insufficiently investigated. Hence, we review the current roles of miRNA-related signaling pathways and recent advances in PCD research and aim to display the potential crosstalk between miRNAs and PCD. The prospects of miRNAs as novel biomarkers and therapeutic targets are also described, which might provide some novel ideas for further studies.

A Selective Separation Mechanism for Mono/divalent Cations and Properties of a Hollow-Fiber Composite Nanofiltration Membrane Having a Positively Charged Surface.

Positively charged nanofiltration (NF) technology is considered a green and low-cost method for mono/divalent cation separation. Nevertheless, the separation rejection mechanisms of these NF membranes have yet to be extensively investigated. In this work, we fabricated a thin-film composite (TFC) hollow-fiber (HF) NF membrane with a positively charged surface via modification of the nascent interfacial polymerization layer using a branched polyethyleneimine (BPEI)/ethanol solution. Then, we extensively investigated its selective separation mechanism for mono/divalent cations. We proposed and proved that there exists a double-charged layer near the membrane surface, which helps to repel the divalent cations selectively via Donnan exclusion while promoting the fast penetration of monovalent cations. Meanwhile, the membrane skin layer is loose and hydrophilic due to the loose BPEI structure and the abundance of amine groups, as well as the changed fabrication conditions. In this way, we achieved very good mono/divalent cation selectivity and relatively high water permeance for the as-prepared HF NF membrane. We also obtained good anti-fouling, anti-scaling, and acid resistance, and long-term stability as well, which are urgently needed during practical application. Furthermore, we successfully amplified this HF NF membrane and proved that it has broad application prospects in mono/divalent cation separation.

MircoRNA-29a in Astrocyte-derived Extracellular Vesicles Suppresses Brain Ischemia Reperfusion Injury via TP53INP1 and the NF-κB/NLRP3 Axis.

Brain ischemia reperfusion injury (BIRI) is defined as a series of brain injury accompanied by inflammation and oxidative stress. Astrocyte-derived extracellular vesicles (EVs) are importantly participated in BIRI with involvement of microRNAs (miRs). Our study aimed to discuss the functions of miR-29a from astrocyte-derived EVs in BIRI treatment. Thus, astrocyte-derived EVs were extracted. Oxygen and glucose deprivation (OGD) cell models and BIR rat models were established. Then, cell and rat activities and pyroptosis-related protein levels in these two kinds of models were detected. Functional assays were performed to verify inflammation and oxidative stress. miR-29a expression in OGD cells and BIR rats was measured, and target relation between miR-29a and tumor protein 53-induced nuclear protein 1 (TP53INP1) was certified. Rat neural function was tested. Astrocyte-derived EVs improved miR-29a expression in N9 microglia and rat brains. Astrocyte-derived EVs inhibited OGD-induced injury and inflammation in vitro, reduced brain infarction, and improved BIR rat neural functions in vivo. miR-29a in EVs protected OGD-treated cells and targeted TP53INP1, whose overexpression suppressed the protective function of EVs on OGD-treated cells. miR-29a alleviated OGD and BIRI via downregulating TP53INP1 and the NF-κB/NLRP3 pathway. Briefly, our study demonstrated that miR-29a in astrocyte-derived EVs inhibits BIRI by downregulating TP53INP1 and the NF-κB/NLRP3 axis.

Dexmedetomidine inhibits endoplasmic reticulum stress to suppress pyroptosis of hypoxia/reoxygenation-induced intestinal epithelial cells via activating the SIRT1 expression.

Dexmedetomidine (Dex) can protect the intestine against ischemia/reperfusion (I/R)-induced injury. Sirtuin 1 (SIRT1) pathway, which could be activated by Dex, was reported to inhibit I/R injury. Pyroptosis plays an important role in intestinal diseases. We aimed to investigate whether Dex could attenuate pyroptosis of hypoxia/reoxygenation (H/R)-induced intestinal epithelial cells via activating SIRT1. The intestinal epithelial cell line IEC-6 with or without SIRT1 knockdown after H/R treatment was exposed to Dex, then cell viability, endoplasmic reticulum stress (ERS), apoptosis, pyroptosis, inflammatory cytokines production and SIRT1 expression were detected. Results showed that Dex treatment had no significant effect on IEC-6 cell viability but rescued the H/R-reduced cell viability. The expression of proteins involved in ERS including Grp78, Gadd153 and caspase 12 was enhanced upon H/R stimulation, but was reversely reduced by Dex. The cell apoptosis increased by H/R was also decreased by Dex. Additionally, Dex inhibited pyroptosis and inflammation, which were markedly promoted upon H/R stimulation. The expression of SIRT1, which was reduced after H/R treatment was also partially rescued by Dex. Finally, the above effects of Dex were all blocked by SIRT1 knockdown. In conclusion, Dex could inhibit H/R-induced intestinal epithelial cells ERS, apoptosis and pyroptosis via activating SIRT1 expression.

Copolymerization of Phenylselenide-Substituted Maleimide with Styrene and Its Oxidative Elimination Behavior.

Selenium-containing monomer monophenyl maleimide selenide (MSM) was synthesized and copolymerized with styrene (St) using reversible addition-fragmentation chain transfer (RAFT) polymerization. Copolymers with controlled molecular weight and narrow molecular weight distribution were obtained. The structure of the copolymer was characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrum, Fourier transform infrared spectroscopy (FT-IR) and Ultraviolet⁻visible spectroscopy (UV-vis) spectroscopy. The copolymer can be oxidized by H2O2 to form carbon-carbon double bonds within the main chain due to the unique sensitivity of selenide groups in the presence of oxidants. Such structure changing resulted in an interesting concentration-related photoluminescence emission enhancement.

Impact of diabetes mellitus on clinical outcomes of pancreatic cancer after surgical resection: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its impact on postoperative outcomes and long-term survival after cancer resection remains controversial. A meta-analysis of published studies was conducted to address this issue. METHODS: An extensive electronic search of four databases was performed for relevant articles. Data were processed for meta-analysis using Review Manager version 5.1. RESULTS: Seventeen observational studies involving 5407 patients were subjected to the analysis. Overall morbidity or any type of complications and mortality were comparable between diabetic and non-diabetic subjects. Overall DM has a significant negative impact on survival (risk ratio [RR], 1.24, 95% confidence interval [CI], 1.05-1.45; P = 0.01). Stratification by the type of DM revealed that new-onset DM (<2 years duration, RR, 1.54, 95% CI, 1.24-1.91; P <0.001) but not long-standing DM (≥2 years duration, RR, 1.74, 95% CI, 0.86-3.52; P = 0.12) was associated with reduced survival. CONCLUSIONS: Diabetes mellitus does not affect perioperative outcomes in patients undergoing surgery for pancreatic cancer. However, new-onset DM confers a negative impact on survival of pancreatic cancer in patients undergoing surgical resection.