Empagliflozin ameliorates ventricular arrhythmias by inhibiting sympathetic remodeling via nerve growth factor/tyrosine kinase receptor A pathway inhibition.

BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) can ameliorate arrhythmias; however, the mechanisms underlying their antiarrhythmic effect remain unclear. Therefore, we aimed to test the hypothesis that the SGLT2i empagliflozin (EMPA) ameliorates ventricular arrhythmias caused by myocardial infarction (MI) by inhibiting sympathetic remodeling. METHODS: Male nondiabetic Sprague-Dawley rats were divided into Sham (n = 10), MI (n = 13), low-EMPA (10 mg/kg/day; n = 13), and high-EMPA (30 mg/kg/day; n = 13) groups. Except for the Sham group, MI models were established by ligation of the left anterior descending coronary artery. After 4 weeks, the hearts were removed. Echocardiography, electrical stimulation, hematoxylin-eosin staining and Masson's staining, Western blotting, immunohistochemistry (IHC), and ELISA were performed. RESULTS: Except for left ventricular posterior wall thickness (LVPWT), EMPA treatment significantly ameliorated the left ventricular anterior wall thickness (LVAWT), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF) in MI rats; there was no statistical difference between the low-EMPA and high-EMPA groups. The threshold for ventricular fibrillation induction and myocardial fibrosis was significantly ameliorated in EMPA-treated rats, and there was no statistical difference between the high-EMPA and low-EMPA groups. EMPA decreased the expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA), tyrosine hydroxylase, and growth-associated protein 43 (GAP43) in the left ventricular infarction margin myocardium of MI rats, especially in the high-EMPA group, with a statistically significant difference between the high-EMPA and low-EMPA groups. High-EMPA significantly decreased noradrenaline (NE) levels in the blood of MI rats; however, there was no statistical difference between the low-EMPA and MI groups. CONCLUSION: EMPA ameliorated the occurrence of ventricular arrhythmias in MI rats, which may be related to a reduction in sympathetic activity, inhibition of the NGF/TrkA pathway, inhibition of sympathetic remodeling, and improvement in cardiac function and cardiac structural remodeling.Graphical abstract, http://links.lww.com/JCM/A659.

The role of iron overload and ferroptosis in arrhythmia pathogenesis.

Ferroptosis is a newly discovered form of programmed cell death triggered by intracellular iron overload, which leads to the accumulation of lipid peroxides in various cells. It has been implicated in the pathogenesis and progression of various diseases, including tumors, neurological disorders, and cardiovascular diseases. The intricate mechanism underlying ferroptosis involves an imbalance between the oxidation and antioxidant systems, disturbances in iron metabolism, membrane lipid peroxidation, and dysregulation of amino acid metabolism. We highlight the key molecular mechanisms governing iron overload and ferroptosis, and discuss potential molecular pathways linking ferroptosis with arrhythmias.

A study on the relationship between gut microbiota and intrahepatic cholestasis of pregnancy.

Objective: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology. Methods: This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3-V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined. Results: Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus, Delftia, and Odoribacter demonstrated positive correlations with ALT. Conclusion: The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified.

Elevated CD4+ T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19.

Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4+ Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2+CD4+ T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4+ Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4+ Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4+ Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.

Agreement of zero-heat-flux thermometry with the oesophageal and tympanic core temperature measurement in patient receiving major surgery.

To identify and prevent perioperative hypothermia, most surgical patients require a non-invasive, accurate, convenient, and continuous core temperature method, especially for patients undergoing major surgery. This study validated the precision and accuracy of a cutaneous zero-heat-flux thermometer and its performance in detecting intraoperative hypothermia. Adults undergoing major non-cardiac surgeries with general anaesthesia were enrolled in the study. Core temperatures were measured with a zero-heat-flux thermometer, infrared tympanic membrane thermometer, and oesophagal monitoring at 15-minute intervals. Taking the average value of temperature measured in the tympanic membrane and oesophagus as a reference, we assessed the agreement using the Bland-Altman analysis and linear regression methods. Sensitivity, specificity, and predictive values of detecting hypothermia were estimated. 103 patients and one thousand sixty-eight sets of paired temperatures were analyzed. The mean difference between zero-heat-flux and the referenced measurements was -0.03 ± 0.25 °C, with 95% limits of agreement (-0.52 °C, 0.47 °C) was narrow, with 94.5% of the differences within 0.5 °C. Lin's concordance correlation coefficient was 0.90 (95%CI 0.89-0.92). The zero-heat-flux thermometry detected hypothermia with a sensitivity of 82% and a specificity of 90%. The zero-heat-flux thermometer is in good agreement with the reference core temperature based on tympanic and oesophagal temperature monitoring in patients undergoing major surgeries, and appears high performance in detecting hypothermia.

Sodium Butyrate Induces Mitophagy and Apoptosis of Bovine Skeletal Muscle Satellite Cells through the Mammalian Target of Rapamycin Signaling Pathway.

Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. Skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited proliferation, promoted apoptosis of BSCs, and promoted mitophagy in a time- and dose-dependent manner in BSCs. In addition, 1 mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA (mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated. The results showed that 1 mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway. In contrast, the addition of PP242, an inhibitor of the mTOR signaling pathway also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1 and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.

Prognosis of a Chinese patient with chronic lymphocytic leukemia who acquired a TP53 mutation following treatment with a BTK inhibitor.

Chronic lymphocytic leukemia (CLL) is a common type of adult leukemia that occurs in Western countries, and its incidence has gradually increased in China in recent years. The characteristics of CLL are highly heterogeneous. Despite promising response rates achieved with targeted therapy, new targets still need to be expanded due to the heterogeneous of disease. Bruton's tyrosine kinase inhibitor (BTKi) has been used in the treatment of TP53 mutation. In this report, we present a case with myeloid differentiation primary response 88 (MYD88) mutation who developed a TP53 mutation after application of BTKi. Here, the patient was CLL unmutated (U-CLL) with MYD88 (L265P) mutation before initial treatment. After traditional treatment, the effect was not good, and BTKi was used for treatment, then TP53 mutation appeared. It is well known that immunoglobulin heavy chain unmutated (IGHV-U) and TP53 mutation in CLL indicate poor prognosis. The case suggests that whenever TP53 mutation occurs, BTKi is the best choice. This result is considered to be related to signal pathways. We aim to add to the collective knowledge by highlighting this rare cases of CLL with MYD88 (L265P) mutation in an Asian patient.

A randomized controlled trial of iliopsoas plane block vs. femoral nerve block for hip arthroplasty.

BACKGROUND: Iliopsoas plane block (IPB) is a novel analgesic technique for hip surgery that retains quadriceps strength. However, evidence from randomized controlled trial is remains unavailable. We hypothesized that IPB, as a motor-sparing analgesic technique, could match the femoral nerve block (FNB) in pain management and morphine consumption, providing an advantage for earlier functional training in patients underwent hip arthroplasty. METHODS: We recruited ninety patients with femoral neck fracture, femoral head necrosis or hip osteoarthritis who were scheduled for unilateral primary hip arthroplasty were recruited and received either IPB or FNB. Primary outcome was the pain score during hip flexion at 4 h after surgery. Secondary outcomes included quadriceps strength and pain scores upon arrival at post anesthesia care unit (PACU) and at 2, 4, 6, 24, 48 h after surgery, the first time out of bed, total opioids consumption, patient satisfaction, and complications. RESULTS: There was no significant difference in terms of pain score during hip flexion at 4 h after surgery between the IPB group and FNB group. The quadriceps strength of patients receiving IPB was superior to those receiving FNB upon arrival at PACU and at 2, 4, 6 and 24 h after surgery. The IPB group showed a shorter first time out of bed compared to the FNB group. However, there were no significant differences in terms of pain scores within 48 h after surgery, total opioids consumption, patient satisfaction and complications between the two groups. CONCLUSION: IPB was not superior to FNB in terms of postoperative analgesia for hip arthroplasty. However, IPB could serve as an effective motor-sparing analgesic technique for hip arthroplasty, which would facilitate early recovery and rehabilitation. This makes IPB worth considering as an alternative to FNB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055493; registration date: January 10, 2022; enrollment date: January 18, 2022; https://www.chictr.org.cn/searchprojEN.html ).

Multi-transcriptomics reveals RLMF axis-mediated signaling molecules associated with bovine feed efficiency.

The regulatory axis plays a vital role in interpreting the information exchange and interactions among mammal organs. In this study on feed efficiency, it was hypothesized that a rumen-liver-muscle-fat (RLMF) regulatory axis exists and scrutinized the flow of energy along the RLMF axis employing consensus network analysis from a spatial transcriptomic standpoint. Based on enrichment analysis and protein-protein interaction analysis of the consensus network and tissue-specific genes, it was discovered that carbohydrate metabolism, energy metabolism, immune and inflammatory responses were likely to be the biological processes that contribute most to feed efficiency variation on the RLMF regulatory axis. In addition, clusters of genes related to the electron respiratory chain, including ND (2,3,4,4L,5,6), NDUF (A13, A7, S6, B3, B6), COX (1,3), CYTB, UQCR11, ATP (6,8), clusters of genes related to fatty acid metabolism including APO (A1, A2, A4, B, C3), ALB, FG (A, G), as well as clusters of the ribosomal-related gene including RPL (8,18A,18,15,13, P1), the RPS (23,27A,3A,4X), and the PSM (A1-A7, B6, C1, C3, D2-D4, D8 D9, E1) could be the primary effector genes responsible for feed efficiency variation. The findings demonstrate that high feed efficiency cattle, through the synergistic action of the regulatory axis RLMF, may improve the efficiency of biological processes (carbohydrate metabolism, protein ubiquitination, and energy metabolism). Meanwhile, high feed efficiency cattle might enhance the ability to respond to immunity and inflammation, allowing nutrients to be efficiently distributed across these organs associated with digestion and absorption, energy-producing, and energy-storing organs. Elucidating the distribution of nutrients on the RLMF regulatory axis could facilitate an understanding of feed efficiency variation and achieve the study on its molecular regulation.

Rumen and Fecal Microbiota Characteristics of Qinchuan Cattle with Divergent Residual Feed Intake.

Residual feed intake (RFI) is one of the indicators of feed efficiency. To investigate the microbial characteristics and differences in the gastrointestinal tract of beef cattle with different RFI, a metagenome methodology was used to explore the characteristics of the rumen and fecal microbiota in 10 Qinchuan cattle (five in each of the extremely high and extremely low RFI groups). The results of taxonomic annotation revealed that Bacteroidetes and Firmicutes were the most dominant phyla in rumen and feces. Prevotella was identified as a potential biomarker in the rumen of the LRFI group by the LEfSe method, while Turicibacter and Prevotella might be potential biomarkers of the HRFI and LRFI group in feces, respectively. Functional annotation revealed that the microbiota in the rumen of the HRFI group had a greater ability to utilize dietary polysaccharides and dietary protein. Association analysis of rumen microbes (genus level) with host genes revealed that microbiota including Prevotella, Paraprevotella, Treponema, Oscillibacter, and Muribaculum, were significantly associated with differentially expressed genes regulating RFI. This study discovered variances in the microbial composition of rumen and feces of beef cattle with different RFIs, demonstrating that differences in microbes may play a critical role in regulating the bovine divergent RFI phenotype variations.

Blood transcriptome reveals immune and metabolic-related genes involved in growth of pasteurized colostrum-fed calves.

The quality of colostrum is a key factor contributing to healthy calf growth, and pasteurization of colostrum can effectively reduce the counts of pathogenic microorganisms present in the colostrum. Physiological changes in calves fed with pasteurized colostrum have been well characterized, but little is known about the underlying molecular mechanisms. In this study, key genes and functional pathways through which pasteurized colostrum affects calf growth were identified through whole blood RNA sequencing. Our results showed that calves in the pasteurized group (n = 16) had higher body height and daily weight gain than those in the unpasteurized group (n = 16) in all months tested. Importantly, significant differences in body height were observed at 3 and 4 months of age (p < 0.05), and in daily weight gain at 2, 3, and 6 months of age (p < 0.05) between the two groups. Based on whole blood transcriptome data from 6-months old calves, 630 differentially expressed genes (DEGs), of which 235 were upregulated and 395 downregulated, were identified in the pasteurized compared to the unpasteurized colostrum groups. Most of the DEGs have functions in the immune response (e.g., CCL3, CXCL3, and IL1A) and metabolism (e.g., PTX3 and EXTL1). Protein-protein interaction analyses of DEGs revealed three key subnetworks and fifteen core genes, including UBA52 and RPS28, that have roles in protein synthesis, oxidative phosphorylation, and inflammatory responses. Twelve co-expression modules were identified through weighted gene co-expression network analysis. Among them, 17 genes in the two modules that significantly associated with pasteurization were mainly involved in the tricarboxylic acid cycle, NF-kappa B signaling, and NOD-like receptor signaling pathways. Finally, DEGs that underwent alternative splicing in calves fed pasteurized colostrum have roles in the immune response (SLCO4A1, AKR1C4, and MED13L), indicative of potential roles in immune regulation. Results from multiple analytical methods used suggest that differences in calf growth between the pasteurized and unpasteurized groups may be due to differential immune activity. Our data provide new insights into the impact of pasteurization on calf immune and metabolic-related pathways through its effects on gene expression.

Identification and characterization of hypothalamic circular RNAs associated with bovine residual feed intake.

Residual feed intake (RFI) is crucial economic indicator used for calculating the feed efficiency of growing beef cattle. circRNA plays an important biological role in gene transcriptional regulation, but little is known about its potential functional regulation underlying RFI phenotypic variation. As the core center of regulation of animal feeding, the hypothalamus is closely associated with RFI. Therefore, the present study aimed to identify the key genes and functional pathways contributing to variance in cattle RFI phenotypes using RNA sequencing from hypothalamic tissue samples, in order to gain insight into the potential regulatory role of circRNAs in bovine RFI phenotypic variation. Differentially expressed genes were detected by RNA sequencing for beef cattle in the high and low RFI groups, followed by GO, KEGG enrichment, and circRNA-miRNA co-expression network analysis. A total of 257 circRNAs were differentially expressed between the two groups, with 128 significantly upregulated and 129 significantly downregulated genes in H group compared to L group. Among them, 9 unique circRNAs were present in group L and 4 unique circRNAs were present in group H. GO and KEGG enrichment analysis of the source genes of the differentially expressed circRNAs revealed that they were mainly involved in metabolic processes, such as cellular metabolic processes, cellular macromolecular metabolic processes, and regulatory pathways related to nutrient metabolism, including protein and amino acid metabolism, as well as vitamin metabolism and pancreatic secretion associated with the animal feeding behavior. The circRNAs detected in this study were mostly novel, and have not been investigated directly to be associated with the RFI phenotype. Interestingly, most miRNAs of differentially expressed circRNAs predicted based on the circRNA-miRNA co-expression network analysis by using top 50 differentially expressed circRNAs and 13 unique circRNAs, have been reported to be related to animal RFIs, implying that circRNAs in bovine hypothalamic tissue may regulate phenotypic variation in RFI through miRNAs. The study results illustrate the complex biological functions of the hypothalamus in regulating feed efficiency and showing the potential role of circRNAs in the feeding behavior regulation of livestock, which would contributing to expanding the understanding of circRNA.

Impact of cigarette smoking on rheumatoid arthritis-associated lung diseases: a retrospective case control study on clinical and radiological features and prognosis.

Our study aimed to investigate the clinical and radiological features and prognosis of male smoker patients with rheumatoid arthritis (RA). We consecutively enrolled male inpatients with RA who received chest HRCT during hospitalization in Peking University Third Hospital from Jan 1st, 2012 to August 1st, 2021. 154 male patients with RA were eligible for analysis, of whom 76.6% (n = 118) were current smokers or had a history of cigarette smoking. Compared to never-smokers, smoker patients had more respiratory symptoms, including cough (31.4% vs 5.6%, p = 0.002) and sputum production (26.3% vs 2.8%, p = 0.002), and a higher positive rate of rheumatoid factor (RF) (77.6% vs 58.8%, p = 0.030). A higher percentage of smoker patients showed emphysema (45.8% vs 16.7%, p = 0.002) and signs of lung fibrosis (51/54, 94.4% vs 7/13, 53.8%, p < 0.001) in those with interstitial lung disease (ILD, n = 67) on chest HRCT. The overall survival rate was different between smoker and never-smoker patients (p = 0.031), but instead of cigarette smoking, lung fibrosis on HRCT was the risk factor for survival of our patients. In conclusion, male patients with RA who were current smokers or had a history of cigarette smoking presented more respiratory symptoms and a higher positive rate of RF. They also showed more emphysema and signs of lung fibrosis on chest HRCT. Cigarette smoking impacted on the overall survival as a confounding factor in this cohort of male patients with RA.

Anesthetic considerations for inadvertent severe hypertension in a patient with osteogenesis imperfecta during the perioperative period.

Osteogenesis imperfecta is a rare genetic syndrome caused by mutations of bone matrix protein type I collagen coding genes, which is characterized by increased bone fragility and recurrent fractures. We report a patient undergoing general anesthesia with additional nerve block for wrist and hip fracture repair. Preoperatively, we were confronted with an inadvertent severe hypertension without significant triggers and history, which prompted us to be vigilant for hypertensive emergencies due to the fragile vessel regulation capacity in osteogenesis imperfecta patients.

Bronchiectasis in patients with antineutrophil cytoplasmic antibody-associated vasculitis: a case control study on clinical features and prognosis.

BACKGROUND: Bronchiectasis was reported in 2%-40% of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), but there were no studies on the prevalence, risk factors and impact of AAV-associated bronchiectasis in Chinese patients. RESEARCH DESIGN AND METHODS: AAV patients were retrospectively enrolled. The clinical, laboratory and imaging features and the prognosis were analyzed and compared between those with and without bronchiectasis. RESULTS: Bronchiectasis was present in 48/212 (22.6%) of our AAV patients, among whom 41 were confirmed in 210 patients (19.5%) who received chest HRCT at the initial diagnosis of AAV. There were more women and fewer smokers in those with bronchiectasis as compared to those without. Cases with positive anti-MPO were more likely to have bronchiectasis (26.2%), and those with bronchiectasis were more likely to be anti-MPO positive (93.8%). Patients who had a diagnosis of bronchiectasis before AAV were more likely to have nervous system involvement, while patients without bronchiectasis had higher 24h proteinuria. The presence of bronchiectasis showed no significant effect on the 1, 3, 5-year survival. CONCLUSIONS: Nearly 20% of patients showed bronchiectasis on chest HRCT at the initial diagnosis of AAV, and positivity of anti-MPO was associated with bronchiectasis in a Chinese cohort of AAV patients.

The effect of continuous adductor canal block combined with distal interspace between the popliteal artery and capsule of the posterior knee block for total knee arthroplasty: a randomized, double-blind, controlled trial.

BACKGROUND: The optimal analgesia for total knee arthroplasty (TKA) requires excellent analgesia while preserving muscle strength. This study aimed to determine the hypothesis that continuous adductor canal block (CACB) combined with the distal interspace between the popliteal artery and the posterior capsule of the knee (IPACK) block could effectively alleviate the pain of the posterior knee, decrease opioids consumption, and promote early recovery and discharge. METHODS: Patients undergoing unilateral, primary TKA were allocated into group CACB+SHAM (receiving CACB plus sham block) or group CACB+IPACK (receiving CACB plus IPACK block). The primary outcome was cumulative opioid consumption. Secondary outcomes included the incidence of postoperative pain originated from the posterior knee, visual analogue scale (VAS) score, range of motion, ambulation distance, and satisfaction for pain management. RESULTS: The incidence of moderate-severe pain of the posterior knee was lower in group CACB+IPACK than that of the group CACB+SHAM at 4 hours (17.1% vs. 42.8%; p = 0.019), 8 hours (11.4% vs. 45.7%; p = 0.001), and 24 hours (11.4% vs. 34.3%; p = 0.046) after TKA. The VAS scores of the posterior knee were lower in group CACB+IPACK than that of the group CACB+SHAM at 4 hours [2 (2) vs. 3 (2-4); p = 0.000], 8 hours [1 (1, 2) vs. 3 (2-4); p = 0.001], and 24 hours [1(0-2) vs. 2 (1-4); p = 0.002] after TKA. The overall VAS scores were lower in group CACB+IPACK than that of the group CACB+SHAM at 4 hours [3 (2, 3) vs. 3 (3, 4); p = 0.013] and 8 hours [2 (2, 3) vs. 3 (2-4); p = 0.032] at rest and 4 hours [3 (3, 4) vs. 4 (4, 5); p = 0.001], 8 hours [3 (2-4) vs. 4 (3-5); p = 0.000], 24 hours [2 (2, 3) vs. 3 (2-4); p = 0.001] during active flexion after TKA. The range of motion (59.11 ± 3.90 vs. 53.83 ± 5.86; p = 0.000) and ambulation distance (44.60 ± 4.87 vs. 40.83 ± 6.65; p = 0.009) were superior in group CACB+IPACK than that of the group CACB+SHAM in postoperative day 1. The satisfaction for pain management was higher in group CACB+IPACK than that of the group CACB+SHAM [9 (8, 9) vs. 8 (7-9); p = 0.024]. There was no difference in term of cumulative opioids consumption between group CACB+IPACK and group CACB+SHAM [120(84-135) vs. 120(75-135); p = 0.835]. CONCLUSION: The combination of CACB and distal IPACK block could decrease the incidences of moderate-severe posterior knee pain, improve the postoperative pain over the first 24 hours after TKA, as well as promoting recovery of motor function. However, the opioids consumption was not decreased by adding distal IPACK to CACB. TRIAL REGISTRATION: This study was registered at Chinese Clinical Trial Registry ( ChiCTR2200059139 ; registration date: 26/04/2022; enrollment date: 16/11/2020; http://www.chictr.org.cn ).

Efficacy of ICS versus Non-ICS Combination Therapy in COPD: A Meta-Analysis of Randomised Controlled Trials.

Background: Several large randomized clinical trials (RCTs) have assessed the efficacy and safety of inhaled corticosteroid (ICS) combination regimens versus non-ICS therapy in patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbation risk with mixed results. Methods: We performed a systematic literature review and meta-analysis of RCTs comparing the effect of ICS-containing combination therapy and non-ICS regimen in patients with COPD. Results: A total of 54 RCTs (N = 57,333) reported treatment effects on various outcomes and were eligible for inclusion. Overall, the number of patients experiencing moderate/severe exacerbations was significantly lower for ICS-containing combination therapy versus non-ICS therapy (RR: 0.86 [95% CI: 0.80-0.93]). The annual rate of exacerbations was also significantly reduced by 22% (0.78 [0.72-0.86]) with ICS-containing versus non-ICS therapy. The annual rate of exacerbations requiring hospitalisation was reduced by 31% versus non-ICS therapy (0.69 [0.54-0.88]); similar reduction was observed for exacerbations requiring oral steroids (0.69 [0.66-0.73]). Overall, the effect on trough FEV1 was comparable between ICS-containing and non-ICS therapies (follow-up: 6-52 weeks); however, a significant improvement in lung function (trough FEV1) was observed for ICS/LABA versus LABA (MD: +0.04 L [0.03-0.05]) and ICS/LABA/LAMA versus LAMA (MD: +0.09 L [0.05-0.13]) regimens. In addition, a significant improvement in QoL was observed with ICS-containing versus non-ICS therapy (MD in SGRQ score: -0.90 [-1.50, -0.31]). Conclusion: This meta-analysis demonstrated that a wide range of patients with COPD could benefit from dual and triple ICS-containing therapy.

The activation of SIRT3 by dexmedetomidine mitigates limb ischemia-reperfusion-induced lung injury.

Background: The lung is one of the most sensitive organs, and is vulnerable to injury caused by limb ischemia-reperfusion (LIR). Dexmedetomidine, an anesthetic adjunct, has been shown to have therapeutic effects on lung injury secondary to LIR. This study aimed to investigate the role of dexmedetomidine in ameliorating LIR-induced lung injury in a mouse model of bilateral hind LIR. Methods: In this study, 75 mice were randomly divided into 5 groups to prepare the LIR model. After the model was established, arterial blood was extracted for blood gas analysis. The pathological changes of lung tissue, lung wet/dry weight ratio, arterial blood gas analysis, detection of myeloperoxidase (MPO) activity, the content of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in oxidative stress indexes, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content and cytochrome c content were measured, and the relative protein expression levels of sirtuin-3 (SIRT3) and apoptosis factor Bcl-2 related X protein (Bax), B-cell Lymphoma 2 (Bcl-2), cleaved caspase 3, and nuclear factor erythroid 2-related factor 2 (Nrf2) and cytoplasmic heme oxygenase-1 (HO-1). Results: Pretreatment with dexmedetomidine dramatically ameliorated LIR-induced lung injury, the wet/dry weight ratio, the arterial blood gas parameters, and enhanced SIRT3 expression. Moreover, dexmedetomidine significantly inhibits ROS and MDA level and restores antioxidant enzyme activities (SOD, GSH-Px). Of note, dexmedetomidine suppressed LIR-induced lung tissue apoptosis by modulating apoptosis-associated protein such as Bax, Bcl-2, and cleaved caspase 3. Moreover, dexmedetomidine inhibited the LIR-induced decreases in MMP, ATP levels, and the release of cytochrome c of LIR to maintain mitochondrial function. Latest study has shown that activating Nrf2 could promote SIRT3 expression to alleviate IR injury. Intriguingly, dexmedetomidine could facilitate nuclear Nrf2 and cytoplasmic HO-1 expression. Conclusions: Our findings suggest that dexmedetomidine protects against LIR-induced lung injury by inhibiting the oxidative response, mitochondrial dysfunction and apoptosis. The mechanism appears to be at least partly mediated through the upregulation of SIRT3 expression.

Analgesic effect of iliopsoas plane block for hip fracture.

BACKGROUND: Hip fracture and surgery are associated with moderate to severe pain, which hampers early mobilization and extends the hospital stay. Femoral nerve block and fascia iliaca compartment block could provide effective postoperative pain relief. Unfortunately, they could weaken the strength of the quadriceps muscle and increase the risk of falls. Iliopsoas plane block (IPB) is a novel motor-sparing regional technique, which targets the sensory branches of the hip joint originating from the femoral nerve. However, the analgesic effect of IPB has not been confirmed yet. CASE PRESENTATION: In the present case series, IPB and lateral femoral cutaneous nerve block were implemented under the guidance of ultrasound for eight patients with hip fractures. The median (IQR) visual analog scale (VAS) score (0-10; 0: no pain, 10: worst pain) decreased from 1.5 (0.25-2) before IPB to 0 (0-0) 0.5h after IPB at rest. The median (IQR) VAS score decreased from 8 (7-8) before IPB to 2 (1-2) 0.5h after IPB during flexion of hip 30°. Pain score was no more than one at rest and three during flexion of the hip 30° within 48h after surgery. Furthermore, the MMT grades of quadriceps strength were no less than four after IPB. CONCLUSIONS: Our case series firstly highlights that IPB might be an effective analgesic technique for hip fracture and surgery, while retaining motor function.