Combination of hyperoxygenation and targeted temperature management improves functional outcomes of post cardiac arrest syndrome irrespective of causes of arrest in rats.

BACKGROUND: The high mortality rates of patients who are resuscitated from cardiac arrest (CA) are attributed to post cardiac arrest syndrome (PCAS). This study evaluated the effect of hyperoxygenation and targeted temperature management (TTM) on PCAS in rats with different causes of CA. METHODS AND RESULTS: One hundred and sixty-eight Sprague-Dawley rats were equally divided into asphyxial and dysrhythmic groups. Animals were further randomized into four subgroups immediately after resuscitation: 1) Normoxia-normothermia (NO-NT): ventilated with 21% oxygen under normothermia; 2) Hyperoxia-normothermia (HO-NT): ventilated with 100% oxygen for 3 h under normothermia; 3) Normoxia-hypothermia (NO-HT): ventilated with 21% oxygen for 3 h under hypothermia; 4) Hyperoxia-hypothermia (HO-HT): ventilated with 100% oxygen for 3 h under hypothermia. Post resuscitation cardiac dysfunction, neurological recovery, and pathological analysis were assessed.For asphyxial CA, HO-NT and HO-HT (68.8% and 75.0%) had significantly higher survival than NO-NT and NO-HT (31.3% and 31.3%). For dysrhythmic CA, NO-HT and HO-HT (81.3% and 87.5%) had significantly higher survival than NO-NT and HO-NT (44.0% and 50.0%). When all of the rats were considered, the survival rate was much higher in HO-HT (81.3%). Compared with NO-NT (57.7 ± 14.9% and 40.3 ± 7.8%), the collagen volume fraction and the proportion of fluoro-jade B-positive area in HO-HT (14.0 ± 5.7% and 28.0 ± 13.3%) were significantly reduced. CONCLUSIONS: The beneficial effects of hyperoxygenation and TTM are dependent on the cause of arrest: hyperoxygenation benefits asphyxial whereas TTM benefits dysrhythmic CA. The combination of hyperoxygenation and TTM could effectively improve the functional outcome of PCAS regardless of the cause of CA.

Role of interleukin­32 in cancer progression (Review).

Interleukin (IL)-32 is induced by pro-inflammatory cytokines and promotes the release of inflammatory cytokines. Therefore, it can promote inflammatory responses. The present review article summarized the role of the receptors required for IL-32 action, the biological function of IL-32 and its mechanism of action in tumors. Moreover, it assessed the significance of aberrant IL-32 expression in associated diseases and analyzed the effects of IL-32 on four key types of cancer: Colorectal, gastric, breast and lung. However, the mechanism of action of IL-32 needs to be further demonstrated by assessing the role of this cytokine in cancer to elucidate novel and reliable targets for future cancer treatments.

Disulfidptosis-related signatures for prognostic and immunotherapy reactivity evaluation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and a nonnegligible health concern on a worldwide scale. Disulfidptosis is a novel mode of cell death, which is mainly caused by the collapse of the actin skeleton. Although many studies have demonstrated that various types of cell death are associated with cancer treatment, the relationship between disulfidptosis and HCC has not been elucidated. METHODS: Here, we mainly applied bioinformatics methods to construct a disulfidptosis related risk model in HCC patients. Specifically, transcriptome data and clinical information were downloaded from the Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) database. A total of 45 co-expressed genes were extracted between the disulfidptosis-related genes (DRGs) and the differential expression genes (DEGs) of liver hepatocellular carcinoma (LIHC) in the TCGA database. The LIHC cohort was divided into two subgroups with different prognosis by k-mean consensus clustering and functional enrichment analysis was performed. Subsequently, three hub genes (CDCA8, SPP2 and RDH16) were screened by Cox regression and LASSO regression analysis. In addition, a risk signature was constructed and the HCC cohort was divided into high risk score and low risk score subgroups to compare the prognosis, clinical features and immune landscape between the two subgroups. Finally, the prognostic model of independent risk factors was constructed and verified. CONCLUSIONS: High DRGs-related risk score in HCC individuals predict poor prognosis and are associated with poor immunotherapy response, which indicates that risk score assessment model can be utilized to guide clinical treatment strategy.

Prognostic Worth of Nrf2/BACH1/HO-1 Protein Expression in the Development of Breast Cancer.

OBJECTIVES: Nrf2/BACH1/HO-1 proteins have been implicated in the development and progression of tumors. However, their clinical relevance in breast cancer remains unclear and understudied. This study evaluated Nrf2/BACH1/HO-1 protein expression and its relationship with age, tumor grade, tumor stage, TNM, ER, PR, HER2, and histologic type. METHODS: 114 female breast cancer and 30 noncancerous tissues were evaluated for Nrf2/BACH1/HO-1 protein expression using immunohistochemistry and Western blot. The relationships between the expression and clinicopathologic factors were assessed using the χ2 test. RESULTS: 74% of the cancerous samples had high Nrf2 protein expression, and 26% of them had low Nrf2 protein expression. Regarding the non-cancer samples, 43% had high Nrf2 protein expression and 57% had low Nrf2 protein expression (p < 0.002). 39% of the cancerous samples had high BACH1 protein expression, and 61% had low BACH1 protein expression. For the non-cancer samples, 80% had high BACH1 protein expression and 20% had low BACH1 protein expression (p < 0.031). 67% of the cancerous samples had high HO-1 protein expression, and 33% had low HO-1 protein expression. However, for the non-cancer samples, 17% of them had high HO-1 protein expression and 83% had low HO-1 protein expression (p < 0.001). The expression of Nrf2 and HO-1 significantly correlated with tumor grade, while BACH1 was significantly associated with tumor stage (p < 0.05). CONCLUSION: Nrf2, BACH1, and HO-1 could be explored as a biomarker for cancer stage, progression, and prognosis.

Sex-specific effect of P2Y2 purinergic receptor on glucose metabolism during acute inflammation.

The sex of an animal impacts glucose sensitivity, but little information is available regarding the mechanisms causing that difference, especially during acute inflammation. We examined sex-specific differences in the role of the P2Y2 receptor (P2Y2R) in glucose flux with and without LPS challenge. Male and female wild-type and P2Y2R knockout mice (P2Y2R-/-) were injected with LPS or saline and glucose tolerance tests (GTT) were performed. P2Y2R, insulin receptor, and GLUT4 transporter gene expression was also evaluated. Female mice had reduced fasting plasma glucose and females had reduced glucose excursion times compared to male mice during GTT. P2Y2R-/- males had significantly decreased glucose flux throughout the GTT as compared to all female mice. Acute inflammation reduced fasting plasma glucose and the GTT area under the curve in both sexes. While both wild-type and P2Y2R-/- male animals displayed reduced fasting glucose in LPS treatment, female mice did not have significant difference in glucose tolerance, suggesting that the effects of P2Y2R are specific to male mice, even under inflammatory conditions. Overall, we conclude that the role for the purinergic receptor, P2Y2R, in regulating glucose metabolism is minimal in females but plays a large role in male mice, particularly in the acute inflammatory state.

Identification of the novel markers of PPAR signalling affecting immune microenvironment and immunotherapy response of lung adenocarcinoma patients.

Peroxisome proliferator-activated receptors (PPARs) are essential for cellular physiological processes. However, there is less research on the PPAR-related genes in lung adenocarcinoma (LUAD). Open-access data were get from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. All the analysis were conducted in the R software based on different R packages. In this study, we gauged the PPAR score employing a set of 72 PPAR-associated genes and probed the biological impact of this score on lung adenocarcinoma (LUAD). Subsequently, we established a unique signature composed of eight PPAR-related genes (ANGPTL4, ACSL3, ADIPOQ, FABP1, SLC27A1, ACOX2, PPARD and OLR1) to forecast the prognosis of LUAD. The signature's effectiveness in predicting survival was validated through the receiver operating characteristic curve in the TCGA-LUAD cohort. As per the pathway enrichment analysis, several crucial oncogenic pathways and metabolic processes were enriched in high-risk individuals. Further, we observed that these high-risk patients exhibited heightened genomic instability. Additionally, compared to the low-risk cohort, high-risk patients demonstrated diminished immune components and function. Intriguingly, high-risk patients exhibited a potential heightened sensitivity to immunotherapy and certain drugs, including Gefitinib, Afatinib, Erlotinib, IAP_5620, Sapitinib, LCL161, Lapatinib and AZD3759. The prognosis model based on eight PPAR-related genes has satisfactory prognosis prediction efficiency. Meanwhile, our results can provide direction for future studies in the relevant aspects.

Clinical characteristics and correlation analysis of IVIG resistance in children with kawasaki disease complicated with hip synovitis: case-control study.

Objective: To investigate the clinical characteristics and risk factors of Kawasaki disease (KD) complicated with hip synovitis. Methods: Children with KD admitted from January 1, 2011, to December 31, 2020, in the KD database of Yuying Children's Hospital Affiliated with Wenzhou Medical University were retrospectively included. We selected KD children with hip synovitis as the case group and KD children without hip synovitis as the control group to analyze the possible risk factors of hip synovitis in KD children. Results: Among 2,871 KD children admitted to our center in recent years, 28 had hip synovitis. In this study 140 KD children were enrolled, including 28 KD children with hip synovitis and 112 children with general KD (within one month of admission). The onset age of KD patients with hip synovitis was 30.92 (23.23-49.99) months, and there were 17 cases of bilateral hip involvement. The course of synovitis (limited movement, joint pain, lameness, unwillingness to stand, etc.) ranged from 1 to 19 days, with an average of (8.8 ± 4.6) days. We treated all KD children with IVIG (Intravenous immunoglobulin) plus aspirin, among which five patients in the case group developed coronary artery damage, six acquired IVIG resistance, and synovial inflammation disappeared within two weeks. Age, weight, length of stay, and incidence of IVIG resistance significantly differed between the two groups (P = 0.001, 0.005, <0.001, and 0.035, respectively). Logistic regression analysis showed that KD combined with hip synovitis was an independent risk factor for developing propyl pellet resistance, with an OR value of 4.625 (95% CI: 1.095, 19.526). Conclusion: KD combined with hip synovitis mainly involves bilateral hip joints, and joint pain and limited movement are the main clinical features. The symptoms are mild and self-limiting. KD combined with hip synovitis is a risk factor for IVIG resistance. Hip synovitis is a good predictor of IVIG resistance.

tsRNA-04002 alleviates intervertebral disk degeneration by targeting PRKCA to inhibit apoptosis of nucleus pulposus cells.

BACKGROUND: Intervertebral disk degeneration (IDD) is a degenerative disease that underlies various musculoskeletal and spinal disorders and is positively correlated with age. tRNA-derived small RNAs (tsRNA), as a new small noncoding RNAs, its function in IDD is unclear. Herein, our goal was to find the key tsRNA that affects IDD independently of age and explore the underlying mechanisms. METHODS: Small RNA sequencing was performed in nucleus pulposus (NP) tissues of traumatic lumbar fracture individuals, young IDD (IDDY) patients, and old IDD (IDDO) patients. The biological functions of tsRNA-04002 in NP cells (NPCs) were investigated by qRT-PCR, western blot, and flow cytometry analysis. The molecular mechanism of tsRNA-04002 was demonstrated by luciferase assays and rescue experiments. Furthermore, the therapeutic effects of tsRNA-04002 on IDD rat model were used and evaluated in vivo. RESULTS: Compared with fresh traumatic lumbar fracture patients, a total of 695 disordered tsRNAs is obtained (398 down-regulated tsRNAs and 297 up-regulated tsRNAs). These disordered tsRNAs were mainly involved in Wnt signaling pathway and MAPK signaling pathway. tsRNA-04002 was an age-independent key target in IDD, which was both lower expressed in IDDY and IDDO groups than control group. Overexpression of tsRNA-04002 restrained inflammatory cytokines IL-1ß and TNF-α expression, increased the COL2A1, and inhibited the NPCs apoptosis. Furthermore, we determined that PRKCA was the target gene of tsRNA-04002 and was negatively regulated by tsRNA-04002. The rescue experiment results suggested that the high expression of PRKCA reversed the inhibitory effect of tsRNA-04002 mimics on NPCs inflammation and apoptosis, and promotive effect of COL2A1. Moreover, tsRNA-04002 treatment dramatically ameliorated the IDD process in the puncture-induced rat model, together with the blockade of PRKCA in vivo. CONCLUSION: Collectively, our results substantiated that tsRNA-04002 could alleviate IDD by targeting PRKCA to inhibit apoptosis of NPCs. tsRNA-04002 may be a novel therapeutic target of IDD progression.

Spinal cord injury-activated C/EBPß-AEP axis mediates cognitive impairment through APP C586/Tau N368 fragments spreading.

Spinal cord injury (SCI) leads to mental abnormalities such as dementia and depression; however, the molecular mechanism of SCI-induced dementia remains a matter of debate. Asparagine endopeptidase (AEP) mediated dementia by enhancing amyloid plaque and Tau hyperphosphorylation, indicating that it played an important role in neurodegeneration. Here we revealed that SCI stimulated AEP activation in mice with T9 contusion injury. Activated-AEP cleaved APP and Tau, resulting in APP C586 and Tau N368 formations, and consequentially accelerated Aß deposit and Tau hyperphosphorylation, respectively. At 9 months following injury, mice demonstrated a severe deterioration in cognitive-behavioral function, which was corroborated by the presence of accumulated AD-specific pathologies. Surprisingly, activated AEP was found in the brains of mice with spinal cord injury. In contrast, AEP knockout reduced SCI-induced neuronal death and neuroinflammation, resulting in cognitive-behavioral restoration. Interestingly, compared to the full-length proteins, truncated Tau N368 and APP C586 were easier to bind to each other. These AEP-processed fragments can not only be induced to pre-formed fibrils, but also amplified their abilities of spreading and neurotoxicity in vitro. Furthermore, as a critical transcription factor of AEP, C/EBPß was activated in injured spinal cord. Elevated C/EBPß level, as well as microglia population and inflammatory cytokines were also noticed in the cortex and hippocampus of SCI mice. These neuroinflammation pathologies were close related to the amount of Tau N368 and APP C586 in brain. Moreover, administration with the AEP-specific inhibitor, compound #11, was shown to decelerate Aß accumulation, tauopathy and C/EBPß level in both spinal cord and brain of SCI mice. Thus, this study highlights the fact that spinal cord injury is a potential risk factor for dementia, as well as the possibility that C/EBPß-AEP axis may play a role in SCI-induced cognitive impairment.

Adenylate Kinase Fused to Spidroin as a Catalyst for Decreasing Leakage out of 3D-Bioprinted Hydrogels and for ATP Regeneration.

Numerous metabolic reactions and pathways use adenosine 5'-triphosphate (ATP) as an energy source and as a phosphorous or pyrophosphorous donor. Based on three-dimensional (3D)-printing, enzyme immobilization can be used to improve ATP regeneration and operability and reduce cost. However, due to the relatively large mesh size of 3D-bioprinted hydrogels soaked in a reaction solution, the lower-molecular-weight enzymes cannot avoid leaking out of the hydrogels readily. Here, a chimeric adenylate-kinase-spidroin (ADK-RC) is created, with ADK serving as the N-terminal domain. The chimera is capable of self-assembling to form micellar nanoparticles at a higher molecular scale. Although fused to spidroin (RC), ADK-RC remains relatively consistent and exhibits high activity, thermostability, pH stability, and organic solvent tolerance. Considering different surface-to-volume ratios, three shapes of enzyme hydrogels are designed, 3D bioprinted, and measured. In addition, a continuous enzymatic reaction demonstrates that ADK-RC hydrogels have higher specific activity and substrate affinity but a lower reaction rate and catalytic power compared to free enzymes in solution. With ATP regeneration, the ADK and ADK-RC hydrogels significantly increase the production of d-glucose-6-phosphate and obtain an efficient usage frequency. In conclusion, enzymes fused to spidroin might be an efficient strategy for maintaining activity and reducing leakage in 3D-bioprinted hydrogels under mild conditions.

Syringaresinol inhibits cardiorenal fibrosis through HSP90 in a cardiorenal syndrome type 2.

BACKGROUND: Syringaresinol processes anti-inflammatory and antioxidative activity. However, the effects of syringaresinol on cardiorenal fibrosis caused by cardiorenal syndrome type 2 (CRS2) are unclear. METHODS: Molecular docking predicted binding activity of syringaresinol to heat shock protein 90 (HSP90). The toxicity of a 4-weeks treatment with 20 mg/kg of syringaresinol was observed by measuring serum pro-inflammatory cytokines levels and by cardiorenal pathology. A CRS2 rad model was established by myocardial infarction using ligation over an 8 week-period. Rats were divided into five groups, including sham, CRS2, pimitespib, syringaresinol, and HSP90 + syringaresinol. Rats were received a 4-weeks daily treatment with 10 mg/kg pimitespib (a HSP90 inhibitor) or 20 mg/kg syringaresinol. Recombinant adeno-associated virus (rAAV) carrying a periostin (PE) promoter driving the expression of wild-type HSP90 (rAAV9-PE-HSP90, 1 × 1011 µg) was treated intravenously once in CRS2 model rats. Cardiorenal function and pathology were assessed. Expressions of HSP90 and TGF-ß1 in the myocardium and kidney were measured by immunohistochemistry and western blotting. RESULTS: Syringaresinol showed good binding activity with HSP90, and no signs of toxicity in rats following treatment. Pimitespib or syringaresinol significantly improved the cardiorenal function and fibrosis in rats with CRS2. Meanwhile, the rAAV9-PE-HSP90 injection obviously blocked the effects of syringaresinol. CONCLUSIONS: Syringaresinol targets HSP90 to suppress CRS2-induced cardiorenal fibrosis, providing a promising therapeutic drug for CRS2.

A secretory system for extracellular production of spider neurotoxin huwentoxin-I in Escherichia coli.

Due to their advantages in structural stability and versatility, cysteine-rich peptides, which are secreted from the venom glands of venomous animals, constitute a naturally occurring pharmaceutical arsenal. However, the correct folding of disulfide bonds is a challenging task in the prokaryotic expression system like Escherichia coli due to the reducing environment. Here, a secretory expression plasmid pSE-G1M5-SUMO-HWTX-I for the spider neurotoxin huwentoxin-I (HWTX-I) with three disulfides as a model of cysteine-rich peptides was constructed. By utilizing the signal peptide G1M5, the fusion protein 6 × His-SUMO-HWTX-I was successfully secreted into extracellular medium of BL21(DE3). After enrichment using cation-exchange chromatography and purification utilizing the Ni-NTA column, 6 × His-SUMO-HWTX-I was digested via Ulp1 kinase to release recombinant HWTX-I (rHWTX-I), which was further purified utilizing RP-HPLC. Finally, both impurities with low and high molecular weights were completely removed. The molecular mass of rHWTX-I was identified as being 3750.8 Da, which was identical to natural HWTX-I with three disulfide bridges. Furthermore, by utilizing whole-cell patch clamp, the sodium currents of hNav1.7 could be inhibited by rHWTX-I and the IC50 value was 419 nmol/L.

Dynamic changes in mechanical properties of the adult rat spinal cord after injury.

Spinal cord injury (SCI), a debilitating medical condition that can cause irreversible loss of neurons and permanent paralysis, currently has no cure. However, regenerative medicine may offer a promising treatment. Given that numerous regenerative strategies aim to deliver cells and materials in the form of tissue-engineered therapies, understanding and characterising the mechanical properties of the spinal cord tissue is very important. In this study, we have systematically characterised the spatiotemporal changes in elastic stiffness (elastic modulus, Pa) and viscosity (drop in peak force, %) of injured rat thoracic spinal cord tissues at distinct time points after crush injury using the indentation technique. Our results demonstrate that in comparison with uninjured spinal cord tissue, the injured tissues exhibited lower stiffness (median 3281 Pa versus 9632 Pa; P < 0.001) but demonstrated elevated viscosity (median 80% versus 57%; P < 0.001) at 3 days postinjury. Between 4 and 6 weeks after SCI, the overall viscoelastic properties of injured tissues returned to baseline values. At 12 weeks after SCI, in comparison with uninjured tissue, the injured spinal cord tissues displayed a significant increase in both elasticity (median 13698 Pa versus 9920 Pa; P < 0.001) and viscosity (median 64% versus 58%; P < 0.001). This work constitutes the first quantitative mapping of spatiotemporal changes in spinal cord tissue elasticity and viscosity in injured rats, providing a mechanical basis of the tissue for future studies on the development of biomaterials for SCI repair. STATEMENT OF SIGNIFICANCE: Spinal cord injury (SCI) is a devastating disease often leading to permanent paralysis. While enormous progress in understanding the molecular pathomechanisms of SCI has been made, the mechanical properties of injured spinal cord tissue have received considerably less attention. This study provides systematic characterization of the biomechanical evolution of rat spinal cord tissue after SCI using a microindentation test method. We find spinal cord tissue behaves significantly softer but more viscous immediately postinjury. As time passes, the lesion site gradually returns to baseline values and then displays pronounced increased viscoelastic properties. As host tissue mechanical properties are a crucial consideration for any biomaterial implanted into central nervous system, our results may have important implications for further studies of SCI repair.

Optimization of Sputtering Process for Medium Entropy Alloy Nanotwinned CoCrFeNi Thin Films by Taguchi Method.

We demonstrate a systematic study optimizing the properties of CoCrFeNi medium entropy alloy (MEA) thin films by tuning the deposition parameters of the pulsed direct current (DC) magnetron sputtering process. The chemical composition and microstructure of thin films were studied with energy dispersive X-ray spectroscopy (EDS), an X-ray diffractometer (XRD) and a transmission electron microscope (TEM). Abundant nanotwins and the dual face-centered cubic-hexagonal close-packed (FCC-HCP) phases were formed in some specimens. The Taguchi experimental method and analysis of variance (ANOVA) were applied to find the optimized parameters. The control factors are five deposition parameters: substrate bias, substrate temperature, working pressure, rotation speed and pulsed frequency. According to the signal-to-noise ratio results, the optimized parameters for low electrical resistivity (98.2 ± 0.8 µΩ·cm), low surface roughness (0.5 ± 0.1 nm) and high hardness (9.3 ± 0.2 GPa) were achieved and verified with confirmed experiments.

Albumin level and progression of coronary artery lesions in Kawasaki disease: A retrospective cohort study.

Background: Albumin (ALB) level is closely associated with the occurrence of intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). The association between ALB level and CALs progression, is critical to the prognosis of KD patients. But little is known about it. This study aims to investigate the effect of the ALB level on CALs progression in KD patients. Methods: A total of 3,479 KD patients from 1 January 2005 to 30 November 2020, in Wenzhou, China were recruited. A total of 319 KD patients who had CALs and ALB data, and finish the follow-up as requested were enrolled in this study. They were classified into the low ALB group and the normal ALB group, divided by 30 g/L. CALs outcomes were classified into two categories according to the CALs changes from the time that CALs were detected within 48 h before or after IVIG treatment to 1 month after disease onset: progressed and no progressed. Multiple logistic regression models were used to assess the independent effect of ALB level on CALs progression among KD patients. Stratified analysis was performed to verify the ALB level on CALs progression among patients in different subgroups. Results: Higher proportion of IVIG resistance (P < 0.001), receiving non-standard therapy (P < 0.001), and receiving delayed IVIG treatment (P = 0.020) were detected in patients with lower ALB level. Patients with lower ALB level had higher C-reactive protein (CRP) level (P = 0.097) and white blood cell count (WBC) (P = 0.036). After adjustment for confounders, patients with lower ALB level had higher odds of CALs progression; the adjusted odds ratio (OR) was 3.89 (95% CI: 1.68, 9.02). Similar results were found using stratification analysis and sensitivity analysis. Male gender and age over 36 months, as covariates in multiple logistic regression models, were also associated with CALs progression. Conclusion: Low ALB level is identified as an independent risk factor for CALs progression in KD patients. Male gender and age over 36 months are also proved to be risk factors for CALs progression. Further investments are required to explore its mechanisms.

Influence of oxygen concentration on the neuroprotective effect of hydrogen inhalation in a rat model of cardiac arrest.

Background: Post-cardiac arrest (CA) brain injury is the main cause of death in patients resuscitated from CA. Previous studies demonstrated that hydrogen inhalation mitigates post-CA brain injury. However, factors affecting the efficacy of hydrogen remain unknown. In the present study, we investigated the influence of oxygen concentration and targeted temperature on neuroprotective effect in a CA rat model of ventricular fibrillation (VF). Methods: Cardiopulmonary resuscitation (CPR) was initiated after 7 min of untreated VF in adult male Sprague-Dawley rats. Immediately following successful resuscitation, animals were randomized to be ventilated with 21% oxygen and 79% nitrogen (21%O2); 2% hydrogen, 21% oxygen, and 77% nitrogen (2%H2 + 21%O2); 2% hydrogen, 50% oxygen, and 48% nitrogen (2%H2 + 50%O2); or 2% hydrogen and 98% oxygen (2%H2 + 98%O2) for 3 h. For each group, the target temperature was 37.5°C for half of the animals and 35.0°C for the other half. Results: No statistical differences in baseline measurements and CPR characteristics were observed among groups. For animals with normothermia, 2%H2 + 50%O2 (123 [369] vs. 500 [393], p = 0.041) and 2%H2 + 98%O2 (73 [66] vs. 500 [393], p = 0.002) groups had significantly lower neurological deficit scores (NDSs) at 96 h and significantly higher survival (75.0 vs. 37.5%, p = 0.033 and 81.3 vs. 37.5%, p = 0.012) than 21%O2 group. For animals with hypothermia, no statistical difference in NDS among groups but 2%H2 + 98%O2 has significantly higher survival than the 21%O2 group (93.8 vs. 56.3%, p = 0.014). Conclusion: In this CA rat model, inhaling 2% hydrogen combined with a high concentration of oxygen improved 96-h survival, either under normothermia or under hypothermia.

Effect of home-based exercise programs with e-devices on falls among community-dwelling older adults: a meta-analysis.

Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72-0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.

Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96-Hour Survival in a Ventricular Fibrillation Rat Model.

Background Myocardial dysfunction is a critical cause of post-cardiac arrest hemodynamic instability and circulatory failure that may lead to early mortality after resuscitation. Trimetazidine is a metabolic agent that has been demonstrated to provide protective effects in myocardial ischemia. However, whether trimetazidine protects against postresuscitation myocardial dysfunction is unknown. Methods and Results Cardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation in Sprague-Dawley rats. Animals were randomized to 4 groups immediately after resuscitation (n=15/group): (1) normothermia control (NTC); (2) targeted temperature management; (3) trimetazidine-normothermia; (4) trimetazidine-targeted temperature management. TMZ was administered at a single dose of 10 mg/kg in rats with trimetazidine. The body temperature was maintained at 34.0°C for 2 hours and then rewarmed to 37.5°C in rats with targeted temperature management. Postresuscitation hemodynamics, 96-hours survival, and pathological analysis were assessed. Heart tissues and blood samples of additional rats (n=6/group) undergoing the same experimental procedure were collected to measure myocardial injury, inflammation and oxidative stress-related biomarkers with ELISA-based quantification assays. Compared with normothermia control, tumor necrosis factor-α, and cardiac troponin-I were significantly reduced, whereas the left ventricular ejection fraction and 96-hours survival rates were significantly improved in the 3 experimental groups. Furthermore, inflammation and oxidative stress-related biomarkers together with collagen volume fraction were significantly decreased in rats undergoing postresuscitation interventions. Conclusions Trimetazidine significantly alleviates postresuscitation myocardial dysfunction and improves survival by decreasing oxidative stress and inflammation in a ventricular fibrillation rat model. A single dose of trimetazidine administrated immediately after resuscitation can effectively improve cardiac function, whether used alone or combined with targeted temperature management.

Effects of Recombinant Human Brain Natriuretic Peptide in Patients with Acute Pulmonary Embolism Complicated with Right Ventricular Dysfunction Who Underwent Catheter-Directed Therapy.

Acute pulmonary embolism (PE) remains a significant cause of cardiovascular morbidity and mortality worldwide. Brain natriuretic peptide (BNP) combined with catheter-directed therapy (CDT) may improve right ventricular (RV) dysfunction and stabilize hemodynamics in acute PE.We retrospectively studied 159 patients with confirmed acute PE who were treated with CDT and admitted to the intensive care unit of our department between September 2016 and May 2020. The patients were divided into the control group and the rhBNP group based on whether to receive recombinant human BNP treatment (rhBNP) or not. The basic characteristics of the patients between the control group and the rhBNP group was systematically compared during admission and follow-up. Risk factors for all-cause mortality within 30 days were determined using multivariate logistic regression analysis.Respiratory rate was found to be significantly lower in the rhBNP group than in the control group. Patients in the rhBNP group had significantly lower levels of white blood cell, C-reactive protein (CRP), D-dimers, troponin I, creatinine, and N-terminal (NT) -proBNP compared with those in the control group. Levels of tricuspid annular plane systolic excursion were significantly higher in the rhBNP group than in the control group. The percentage of patients with rehospitalization readmission due to PE differed significantly between the control group and the rhBNP group. On the basis of the multivariate regression analysis, CRP, creatinine, troponin I, and NT-proBNP were independent factors of all-cause mortality in 30 days.rhBNP is effective in the treatment of patients with RV dysfunction caused by acute PE who underwent CDT, which may be an alternative treatment option for improving clinical prognosis.

Clinical and Radiographic Outcomes of Combined Posterior Transfacet Screw Fixation and Anterior Cervical Discectomy and Fusion Surgery for Unilateral Cervical Facet Fracture with Traumatic Disc Herniation: A Retrospective Cohort Study.

INTRODUCTION: Combined lateral mass screw-rod (LMSR) fixation and anterior cervical discectomy and fusion (ACDF) surgery is currently the most widely described and accepted procedure for subaxial cervical facet fracture with traumatic disc herniation. Recent biomechanical studies have demonstrated that the use of transfacet screw (TFS) can be considered as a simple alternative method to LMSR. However, to date, little is known about the feasibility and effectiveness of TFS in the combined approach. The aim of this study was to compare the clinical and radiographic results of TFS + ACDF surgery and LMSR + ACDF surgery, and to provide a less invasive alternative technique for spine surgeons. METHOD: We retrospectively reviewed patients with unilateral cervical facet fracture with traumatic disc herniation who had undergone TFS + ACDF (N = 36) or LMSR + ACDF (N = 34) with a minimum 2-year follow-up. Clinical assessments, which included American Spinal Injury Association impairment scale (AIS), visual analog scale for neck pain (VASSNP) score and patient satisfaction, were made before surgery and at follow-up. For the radiographic outcomes, the instability parameters of segmental kyphosis and sagittal translation were measured. RESULTS: The demographic characteristics of the two groups of patients were similar. In terms of clinical outcomes, both two groups were associated with significant improvements at the final follow-up. There were no significant between-group differences in VASSNP score or patient satisfaction (both P > 0.05). The LMSR + ACDF group suffered more blood loss and had longer operative time (mean 206.0 ml; mean 274.4 min, respectively) than in the TFS + ACDF group (mean 110.0 ml; mean 142.8 min, respectively) (P < 0.001 for both comparisons). For the radiographic results, the segmental kyphosis and sagittal translation were significantly corrected after surgery in both groups (P < 0.001 for both groups), and no significant differences were found between groups at the last follow-up (P > 0.05). CONCLUSION: In the absence of any self-evident clinical and radiographic benefits of one technique over the other (TFS + ACDF vs. LMSR + ACDF), we recommend combined TFS + ACDF surgery as a safe and less invasive alternative treatment for unilateral cervical facet fractures with traumatic disc herniation, as it was associated with a shorter duration of surgery and lower estimated blood loss than LMSR + ACDF surgery.