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Spermatogonial stem cells (SSCs) are the only adult stem cells capable of passing genetic information to offspring through their ability to both self-renew and differentiate into mature spermatozoa. SSCs can be transplanted to establish donor-derived spermatogenesis in recipient animals, thus offering a novel reproductive tool for multiplication of elite individual animals to benefit livestock production. An optimal SSC culture in vitro can benefit various SSC-based studies and applications, such as mechanistic study of SSC biology, SSC transplantation process, and SSC-based transgenesis technique. However, except some model rodent animals, SSC culture remains an inefficient and unstable process. We here studied a workflow to isolate, purify, and in vitro culture porcine SSCs from neonatal pig testes. Pig testicular cells were dissociated by two step enzymatic digestion with collagenase type IV and trypsin. We enriched the spermatogonia from the testicular cell mix by differential plating for at least 3 times to remove firmly attached non-SSCs. We then tested the optimal culture medium formula by supplementation of different growth factors to the basic medium (DMEM/F12 + 1% FBS), and found that a combination of 20 ng/mL GDNF, 10 ng/mL LIF, 20 ng/mL FGF2, and 20 ng/mL IGF1 had the best effect on SSC growth in our defined experimental system. In the presence of 4 growth factors without specific feeders, the purified SSCs can be cultured in poly-L-lysine- and laminin-coated dishes for 28 days, and remain preserving a continuous proliferation without losing the undifferentiated spermatogonial phenotype.

Continuous renal replacement therapy (CRRT) was currently demonstrated to be an effective way to induce fast hypothermia and had proective effects on cardiac dysfunction and brain damage after cardiac pulmonary resuscitation (CPR). In the present study, we aimed to investigate the influence of extracorporeal circuit cooling using CRRT on renal and intestinal damage after CPR based on a porcine model.32 pigs were subjected to ventricular fibrillation for 8 min, followed by CPR for 5 min before defibrillation. All were randomized to receive extracorporeal circuit cooling using CRRT (CRRT, n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (n = 5) at 5 min post resuscitation. Pigs in the CRRT group were cooled by 8-h CRRT cooling with the infusion line initially submerged in 4 °C of ice water and 16-h SC, while in the SC group by a 24-h SC. Temperatures were maintained at a normal range in the other two groups. Biomarkers in serum were measured at baseline and 1, 3, 6, 12, 24 and 30 h post resuscitation to assess organ functions. Additionally, tissues of kidney and intestine were harvested, from which the degree of tissue inflammation, oxidative stress, and apoptosis levels were analyzed.The blood temperature decreased faster by extracorporeal circuit cooling using CRRT than SC (9.8 ± 1.6 vs. 1.5 ± 0.4 °C/h, P0.01). Post-resuscitation renal and intestinal injury were significantly improved in the 2 hypothermic groups compared to the NT group. And the improvement was significantly greater in animals received extracorporeal circuit cooling than those received surface cooling, from both the results of biomarkers in serum and pathological evidence.Fast hypothermia induced by extracorporeal circuit cooling was superior to. surface cooling in mitigating renal and intestinal injury post resuscitation.

Accidental carbon monoxide poisoning (ACOP) is the most common occupational toxic disease, but related data are scarce or non-existent in many countries. This article investigates the global burden of ACOP based on the Global Burden of Disease Study 2019 (GBD 2019) and the World Bank database. In our study, numbers and age-standardized rates of ACOP prevalence, incidence, deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were analyzed at global, regional, and national level. Besides, the estimated annual percentage change (EAPC) of age-standardized rates were calculated by generalizing the linear model. Age, sex, and Socio-demographic Index (SDI) are included to access their internal relevance. Globally, in 2019, there were approximately 0.97 million ACOP incidence cases (95% CI 0.66 million to 1.4 million), and 41,142 (95% UI 32,957 to 45,934) people died from it. Compared with 1990, the morbidity and mortality of ACOP in 2019 are on a downward trend. By sexes, from 1990 to 2019, females have higher morbidity and lower mortality. This correlation enables us to evaluate the level and status of public health services in various countries. We also evaluated the correlation between ACOP and economic parameters and use newly released machine learning tool-AutoGluon to predict the epidemiology of ACOP. The results of this study can be used by the health authorities to consider the burden of ACOP that could be addressed with preventive and therapeutic measures.

Various human motions yield stimuli from low-pressure (0–10 kPa) to high-pressure level (100–300 kPa). However, previous flexible pressure sensors are unable to detect various human motions from low to high-pressure stimuli, thus are unfavorable for the facile and integrated design of sensing system. Herein a novel flexible pressure sensor with a tunable and large pressure-detecting range is produced by simply infusing magnetic carboxyl iron particle (CIP)/silicone resin into carbon sponge (CS). Attributed to the magnetorheological effect, the upper pressure-detecting limit of the CS/CIP/silicone sensor in a frequency of 0.01–5 Hz is significantly increased from 180 to 330 kPa in the presence of magnetic field, while a lower pressure-detecting limit of 70 Pa is obtained in the absence of magnetic field, thus covering the whole pressure-detecting range for various human activities. The CS/CIP/silicone sensor in monitoring various human motions with low to high-pressure stimuli is demonstrated by recording breathing, arm movement, walking, lifting and grasping, consecutively. Characterized by high flexibility, low cost and easy manufacturing, the current strategy is highly provoking for the development of pressure sensors adapted to human motions of different pressure levels in a wide range.

The aim of this study was to study the regulation of abdominal fat deposition by DL-α-tocopherol acetate (vitamin E) in broilers. Diets supplemented with 50 IU vitamin E significantly diminished abdominal fat deposition in broilers at day 35. Transcriptome sequencing results for abdominal fat tissues of the control (FC) and 50 IU vitamin E-supplemented (FT) groups identified 602 differentially expressed genes (DEGs), which were enriched in cellular process, cell and cell part, and binding Gene Ontology terms. Pathway functional analysis revealed that the DEGs were enriched in 42 metabolic pathways. Notably, the most enriched pathway, fatty acid biosynthesis, was found to play a key role in lipid metabolism. Further, the key regulators of lipid metabolism, including fatty acid synthase, acetyl-CoA carboxylase alpha, and acyl-CoA synthetase long-chain family member 1, demonstrated decreased expression following vitamin E supplementation. Herein, we have identified pathways and genes regulated by vitamin E, thereby providing novel insights into the nutrients regulating abdominal fat deposition in broilers.

Purpose The study aimed to examine the changing incidence of geriatric trauma and evaluate the predictive ability of different scoring tools for in-hospital mortality in geriatric trauma patients. Methods Annual reports released by the National Trauma Database (NTDB) in the USA from 2005 to 2015 and the Trauma Register DGU® in Germany from 1994 to 2012 were analyzed to examine the changing incidence of geriatric trauma. Secondary analysis of a single-center cohort study conducted among 311 severely injured geriatric trauma patients in a level I trauma center in Switzerland was completed. According to the in-hospital survival status, patients were divided into the survival and non-survival group. The differences of the ISS (injury severity score), NISS (new injury severity score), TRISS (Trauma and Injury Severity Score), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SPAS II (simplified acute physiology score II) between two groups were evaluated. Then, the areas under the receiver-operating characteristic curve (AUC-ROC) of different scoring tools for the prediction of in-hospital mortality in geriatric trauma patients were calculated. Results The analysis of the NTDB showed that the increase in the number of geriatric trauma ranged from 18 to 30% between 2005 and 2015. The analysis of the DGU® showed that the mean age of trauma patients rose from 39.11 in 1993 to 51.10 in 2013, and the proportion of patients aged ≥ 60 years rose from 16.5 to 37.5%. The findings from the secondary analysis showed that 164 (52.73%) patients died in the hospital. The ISS, NISS, APACHE II, and SAPS II in the death group were significantly higher than those in the survival group, and the TRISS in the death group was significantly lower than those in the survival group. The AUCs of the ISS, NISS, TRISS, APACHE II, and SAPS II for the prediction of in-hospital mortality in geriatric trauma patients were 0.807, 0.850, 0.828, 0.715, and 0.725, respectively. Conclusion The total number of geriatric trauma is increasing as the population ages. The accuracy of ISS, NISS and TRISS was higher than the APACHE II and SAPS II for the prediction of in-hospital mortality in geriatric trauma patients.

Background: Ischemic heart disease is the leading cause of morbidity and mortality worldwide. Ischemic preconditioning (IPC) is the most powerful intrinsic protection against cardiac ischemia/reperfusion injury. Previous studies have shown that a multifunctional TRIM family protein, MG53 (mitsugumin 53; also called TRIM72), not only plays an essential role in IPC-mediated cardioprotection against ischemia/reperfusion injury but also ameliorates mechanical damage. In addition to its intracellular actions, as a myokine/cardiokine, MG53 can be secreted from the heart and skeletal muscle in response to metabolic stress. However, it is unknown whether IPC-mediated cardioprotection is causally related to MG53 secretion and, if so, what the underlying mechanism is. Methods: Using proteomic analysis in conjunction with genetic and pharmacological approaches, we examined MG53 secretion in response to IPC and explored the underlying mechanism using rodents in in vivo, isolated perfused hearts, and cultured neonatal rat ventricular cardiomyocytes. Moreover, using recombinant MG53 proteins, we investigated the potential biological function of secreted MG53 in the context of IPC and ischemia/reperfusion injury. Results: We found that IPC triggered robust MG53 secretion in rodents in vivo, perfused hearts, and cultured cardiac myocytes without causing cell membrane leakage. Mechanistically, IPC promoted MG53 secretion through H 2 O 2 -evoked activation of protein kinase-C-δ. Specifically, IPC-induced myocardial MG53 secretion was mediated by H 2 O 2 -triggered phosphorylation of protein kinase-C-δ at Y311, which is necessary and sufficient to facilitate MG53 secretion. Functionally, systemic delivery of recombinant MG53 proteins to mimic elevated circulating MG53 not only restored IPC function in MG53-deficient mice but also protected rodent hearts from ischemia/reperfusion injury even in the absence of IPC. Moreover, oxidative stress by H 2 O 2 augmented MG53 secretion, and MG53 knockdown exacerbated H 2 O 2 -induced cell injury in human embryonic stem cell–derived cardiomyocytes, despite relatively low basal expression of MG53 in human heart. Conclusions: We conclude that IPC and oxidative stress can trigger MG53 secretion from the heart via an H 2 O 2 –protein kinase-C-δ–dependent mechanism and that extracellular MG53 can participate in IPC protection against cardiac ischemia/reperfusion injury.

Aim The research aims to assess nurses' willingness to participate in care of patients with coronavirus disease 2019 (COVID-19) in China and to identify its associated factors. Background Along with the increasing number of infections, the world has paid widespread attention to COVID-19. Methods This cross-sectional study used a convenience sampling method that included a demographics questionnaire and the Nurses' Perceived Professional Benefits Questionnaire. The survey was distributed to 1,787 nurses from 36 hospitals in China. Results In total, 1,176 questionnaires were usable for this research. 92.79% of nurses were willing to participate in care of patients with COVID-19. Intensive care unit (ICU) nurses were less willing to participate, while surgical nurses were more willing to participate. In addition, nurses with high positive professional perception scores were more willing to participate than those with low scores. Conclusion The vast majority of nurses were willing to participate in care of patients with COVID-19 in China. Surgical nurses and nurses with positive professional perceptions are more likely to be willing to participate in treatment. Implications for nursing management To increase nurses' willingness to participate in care of patients with COVID-19, improving the sense of perceived professional benefits, offering salary and offering paid sick leave for nursing staff are effective ways. In addition, raising the awareness of infectious diseases and increased pre-disaster training during infectious diseases is critical.

C16 peptide and angiopoietin-1 (Ang-1) have been found to have anti-inflammatory activity in various inflammation-related diseases. However, their combined role in acute respiratory distress syndrome (ARDS) has not been investigated yet. The objective of this study was to investigate the effects of C16 peptide and Ang-1 in combination with lipopolysaccharide (LPS)-induced inflammatory insult in vitro and in vivo. Human pulmonary microvascular endothelial cells and human pulmonary alveolar epithelial cells were used as cell culture systems, and an ARDS rodent model was used for in vivo studies. Our results demonstrated that C16 and Ang-1 in combination significantly suppressed inflammatory cell transmigration by 33% in comparison with the vehicle alone, and decreased the lung tissue wet-to-dry lung weight ratio to a maximum of 1.53, compared to 3.55 in the vehicle group in ARDS rats. Moreover, C + A treatment reduced the histology injury score to 60% of the vehicle control, enhanced arterial oxygen saturation (SO2), decreased arterial carbon dioxide partial pressure (PCO2), and increased oxygen partial pressure (PO2) in ARDS rats, while also improving the survival rate from 47% (7/15) to 80% (12/15) and diminishing fibrosis, necrosis, and apoptosis in lung tissue. Furthermore, when C + A therapy was administered 4 h following LPS injection, the treatment showed significant alleviating effects on pulmonary inflammatory cell infiltration 24 h postinsult. In conclusion, our in vitro and in vivo studies show that C16 and Ang-1 exert protective effects against LPS-induced inflammatory insult. C16 and Ang-1 hold promise as a novel agent against LPS-induced ARDS. Further studies are needed to determine the potential for C16 and Ang-1 in combination in treating inflammatory lung diseases.

Hepatocellular carcinoma (HCC) is a highly malignant tumor associated with a poor prognosis, and the molecular mechanisms remain poorly understood. KIAA1522 expression is upregulated in various types of tumor tissue; however, its function remains unknown in HCC. Bioinformatics analysis was undertaken using Oncomine, OncoLnc and other databases, in order to determine KIAA1522 expression in HCC and to analyze its association with postoperative prognosis. Reverse transcription-quantitative PCR was performed to detect KIAA1522 mRNA expression in primary HCC and adjacent normal tissues, while KIAA1522 protein expression was assessed via immunohistochemical staining. KIAA1522 expression and clinicopathological characteristics of primary HCC were evaluated, and their association with patient prognosis was analyzed. The Oncomine database results indicated that KIAA1522 expression in HCC and normal liver tissues was significantly different. RT-qPCR analysis demonstrated that KIAA1522 mRNA expression was significantly higher in HCC tissues compared with that in adjacent normal tissues. Immunohistochemical analysis indicated that expression rate of KIAA1522 protein was significantly higher in primary HCC tissues compared with that in normal liver tissues. The OncoLnc database results demonstrated that KIAA1522 expression was significantly associated with short-term survival. Kaplan-Meier survival analysis indicated that high KIAA1522 protein expression was significantly associated with short-term survival for patients with HCC. Multivariate Cox regression analysis demonstrated that tumor size, Tumor-Node-Metastasis stage and high KIAA1522 protein expression were independent predictors of a poor prognosis in patients with primary HCC. Furthermore, high KIAA1522 expression was significantly associated with postoperative survival time in primary HCC, and thus may be a potential molecular marker for prognosis in patients with this cancer type.

Background Lung ultrasound is increasingly used in critically ill patients as an alternative to bedside chest radiography, but the best training method remains uncertain. This study describes a training curriculum allowing trainees to acquire basic competence. Methods This multicenter, prospective, and educational study was conducted in 10 Intensive Care Units in Brazil, China, France and Uruguay. One hundred residents, respiratory therapists, and critical care physicians without expertise in transthoracic ultrasound (trainees) were trained by 18 experts. The main study objective was to determine the number of supervised exams required to get the basic competence, defined as the trainees’ ability to adequately classify lung regions with normal aeration, interstitial–alveolar syndrome, and lung consolidation. An initial 2-h video lecture provided the rationale for image formation and described the ultrasound patterns commonly observed in critically ill and emergency patients. Each trainee performed 25 bedside ultrasound examinations supervised by an expert. The progression in competence was assessed every five supervised examinations. In a new patient, 12 pulmonary regions were independently classified by the trainee and the expert. Results Progression in competence was derived from the analysis of 7,330 lung regions in 2,562 critically ill and emergency patients. After 25 supervised examinations, 80% of lung regions were adequately classified by trainees. The ultrasound examination mean duration was 8 to 10 min in experts and decreased from 19 to 12 min in trainees (after 5 vs. 25 supervised examinations). The median training duration was 52 (42, 82) days. Conclusions A training curriculum including 25 transthoracic ultrasound examinations supervised by an expert provides the basic skills for diagnosing normal lung aeration, interstitial–alveolar syndrome, and consolidation in emergency and critically ill patients. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Purpose The aim of this study was to explore the effects of an enteral nutrition (EN) feeding protocol in critically ill patients. Methods This was a prospective multi-center before-after study. We compared energy related and prognostic indicators between the control group (pre-implementation stage) and intervention group (post-implementation stage). The primary endpoint was the percentage of patients receiving EN within 7 days after ICU admission. Results 209 patients in the control group and 230 patients in the intervention group were enrolled. The implementation of the EN protocol increased the percentage of target energy reached from day 3 to day 7, and the difference between two groups reached statistical significance in day 6 (P = .01) and day 7 (P = .002). But it had no effects on proportion of patient receiving EN (P = .65) and start time of EN (P = .90). The protocol application might be associated with better hospital survival (89.1% vs 82.8%, P = .055) and reduce the incidence of EN related adverse (P = .004). There was no difference in ICU length of stay, duration of mechanical ventilation and ICU cost. Conclusion The implementation of the enteral feeding protocol is associated with improved energy intake and a decreased incidence of enteral nutrition related adverse events for critically ill patients, but it had no statistically beneficial effects on reducing the hospital mortality rate. Trial registration ClinicalTrials.gov , NCT02976155 . Registered November 29, 2016- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02976155 .

NG2 immunopositive progenitor cells, also simply termed as NG2 glia and thought mainly to be oligodendrocyte precursor cells (OPCs), form synaptic connections with neurons in gray and white matters of brain. One of the most classical features of oligodendrocyte lineage cells is myelination, which will favor neuronal signaling transmission. Thus, is there a causal link between the specific synapses of neuron-NG2 glia and myelination? Building on this, here, we will discuss several relevant issues. First, in order to understand the synapses, it is necessary to integrate the definite inputs onto NG2 glia. We show that the synaptic activities and myelination are not synchronized, so the synapses are more likely to regulate early development of NG2 glia and prepare for myelination. Furthermore, several studies have suggested that the synapses also play a role in recovery of pathological conditions, such as multiple sclerosis (MS). Therefore, elucidating the activities of neuron-NG2 glia synapses will be beneficial for both physiological and pathological conditions. Graphical abstract The existence of neuron-NG2 glia synapses reveals that the neuronal activities projecting to NG2 glia is an elaborate regulation, and the signaling from neurons to NG2 glia is frequent in early stage. The neuron-NG2 glia synapses indirectly provide a basic condition to support myelination by extrasynaptic communication. The neuron-NG2 glia synapses also promote remyelination, and it occurs similar to physiological conditions.

Purpose: To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury. Methods: Twenty female healthy goats were randomly divided into three groups by different driving pressures: 4.0 MPa group (n = 4), 4.5 MPa group (n = 12) and 5.0 MPa group (n = 4). The severe blast lung injury model of goats was established using a BST-I bio-shock tube. Vital signs (respiration, heart rate and blood pressure), lung ultrasound score (LUS), PO2/FiO2 and extravascular lung water (EVLW) were measured before injury (0 h) and at 0.5 h, 3 h, 6 h, 9 h, 12 h after injury. Computed tomography scan was performed before injury (0 h) and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume. The correlation of LUS with PaO2/FiO2, EVLW, and lung injury ratio (lesion volume/total lung volume*100%) was analyzed. All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination. Statistical analysis was performed by the SPSS 22.0 software. The measurement data were expressed as mean ± standard deviation. The means of two samples were compared using independent-sample t-test. Pearson correlation analysis was conducted. Results: (1) At 12 h after injury, the mortality of goats was 0, 41.67% and 100% in the 4.0 Mpa, 4.5 MPa and 5.0 MPa groups, respectively; the area of pulmonary hemorrhage was 20.00% ± 13.14% in the 4.0 Mpa group and 42.14% ± 15.33% in the 4.5 MPa group. A severe lung shock injury model was established under the driving pressure of 4.5 MPa. (2) The respiratory rate, heart rate, LUS and EVLW were significantly increased, while PaO2/FiO2 was significantly reduced immediately after injury, and then they gradually recovered and became stabilized at 3 h after injury. (3) LUS was positively correlated with EVLW (3 h: r = 0.597, 6 h: r = 0.698, 9 h: r = 0.729; p

Background Since the trauma knowledge of trauma providers correlates with the outcomes of injured patients, this study aims to assess the socio-demographic characteristics and levels of trauma knowledge of trainees in the China trauma care training (CTCT) program in addition to their post-course test results to provide support for the development of trauma care training programs and trauma systems in China. Methods A cross-sectional study was conducted by collecting demographic information, hospital-related information and trauma knowledge of the trainees from 19 regions in China. All participants were assessed by questionnaires collecting the socio-demographic data, the trauma care knowledge levels and the information of the hospitals. Results There were 955 males (78.9%) and 256 females (21.1%) enrolled. Among them, 854 were physicians (70.5%), 357 were registered nurses (29.5%). In addition, 64 of them also played an administrative role in the hospitals (5.3%). The score of the trainees who were members of the emergency department staff (72.59 ± 14.13) was the highest among the scores of all the personnel surveyed, followed by those of the trainees from the intensive care unit (ICU) (71.17 ± 12.72), trauma surgery department (67.26 ± 13.81), orthopedics department (70.36 ± 14.48), general surgery department (69.91 ± 14.79) and other departments (69.93 ± 16.91), P = 0.031. The score of the professors (73.09 ± 15.05) was higher than those of the associate professors (72.40 ± 14.71), lecturers (70.07 ± 14.25) and teaching assistants (67.58 ± 15.16), P P = 0.001. The mean scores before and after the training were 71.02 ± 14.82 and 84.24 ± 13.77, respectively, P < 0.001. The mean score of trauma knowledge after the training of trainees from different provinces and with different educational backgrounds was higher than that before the training, with a statistically significant difference (P Conclusions The level of trauma knowledge of trauma care providers was associated with their department, professional position and previous participation in related academic conferences. Trauma care experience and participation in academic lectures and training program including CTCT may effectively improve individuals’ level of trauma knowledge.

Purpose In this study, we established the inflammatory factor grade system (IFGs) based on the hepatocellular carcinoma (HCC) microenvironment to investigate the role of inflammatory factor grade (IFG) in predicting the prognosis of patients with American Joint Committee on Cancer (AJCC) stage I-II. Patients and methods We enrolled 87 HCC patients with AJCC stage I-II who underwent R0 resection between 2000 and 2012 and had paraffin-embedded specimens. Immunohistochemistry (IHC) was performed to investigate the expression of 12 inflammatory factors and then to establish the IFGs (grade A or B) based on the IHC data. Subsequently, Kaplan-Meier and Cox univariate/multivariate survival analyses were performed to examine the potential prognostic significance. Results Higher IFG (IFG-B) is significantly associated with greater tumor size (P=0.037), and IFG-B predicts a worse disease-free survival (DFS, P

Alternative splicing (AS) event is a novel biomarker of tumor tumorigenesis and progression. However, the comprehensive analysis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is lacking. Differentially expressed analysis was used to identify the differentially expressed alternative splicing (DEAS) events between HCC or ICC tissues and their normal tissues. The correlation between DEAS events and functional analyses or immune features was evaluated. The cluster analysis based on DEAS can accurately reflect the differences in the immune microenvironment between HCC and ICC. Forty-five immune checkpoints and 23 immune features were considered statistically significant in HCC, while only seven immune checkpoints and one immune feature in ICC. Then, the prognostic value of DEAS events was studied, and two transcripts with different basic cell functions (proliferation, cell cycle, invasion, and migration) were produced by ADHFE1 through alternative splicing. Moreover, four nomograms were established in conjunction with relevant clinicopathological factors. Finally, we found two most significant splicing factors and further showed their protein crystal structure. The joint analysis of the AS events in HCC and ICC revealed novel insights into immune features and clinical prognosis, which might provide positive implications in HCC and ICC treatment.

Lactate is not only an energy metabolite for neurons, but also serves as a molecule regulator affecting neuronal activity through its receptor, G protein-coupled receptor 81 (GPR81). This receptor can trigger cellular signaling pathways, such as phosphatidylinositol 3 kinase /protein kinase B (PI3K/Akt) pathway. Particularly, lactate deficit and inhibition of PI3K/Akt pathway were observed to be related with early synaptic dysfunction in Alzheimer’s disease (AD). In addition, amyloid beta (Aβ) is toxic to neurons, while in vitro lactate administration of neurons can resist against this toxicity. Hence, this work focuses on the effect of lactate deficiency on Aβ production, suggesting that lactate decrease can inhibit GPR81-PI3K/Akt pathway, and then reduce deoxyribonucleic acid methyltransferase 1 (DNMT1) expression, further resulting in increase of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and Aβ production. Based on the analysis of results, this study primarily proves that lactate reduction suppresses its downstream GPR81-PI3K/Akt pathway, which decreases the expression of DNMT1 through regulating cyclic-adenosine-monophosphate response element-binding protein (CREB)/P300. Then, it is proved that DNMT1 reduction can lead to the increase of BACE1 and Aβ accumulation in AD. At last, in vitro experiment recognizes that lactate directly activates GPR81-PI3K/Akt pathway. Thus, this study provides a novel insight in Aβ production in relation with lactate deficit at early stage of AD. Particularly, it is suggested that extra addition of lactate might be protective for neurons targeting Aβ clearance in early treatment of AD.

PurposeThe enzyme aldehyde dehydrogenase 2 (ALDH2) has been shown to protect the heart and brain from oxidative stress injury, and this effect is related to the inhibition of pyroptosis. In the present study, we hypothesised that the ALDH2 activator N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichloro-benzamide (Alda-1) would mitigate cardiac and neurological injury postresuscitation in a preclinical swine model of CA.MethodsFollowing 8 minutes of untreated ventricular fibrillation, and another 8 minutes of cardiopulmonary resuscitation (CPR), the swine randomly received either Alda-1 (0.88 mg/kg, n = 6) or saline (n=5) after restoration of spontaneous circulation (ROSC). Hemodynamic parameters and cardiac function were monitored, and serial blood samples were collected postresuscitation to detect biomarkers of cardiac and neurological injury. At 24 hours postresuscitation, first, neurological scores were evaluated, and then, the swine were sacrificed and pyroptosis-related proteins, proinflammatory cytokines, and oxidative stress were assessed in heart and brain samples.ResultsCardiac and neurological injury were significantly improved in the Alda-1 group compared with the CPR group postresuscitation. In addition, after treatment with Alda-1, the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Gasdermin D (GSDMD), and proinflammatory cytokine levels were markedly suppressed. Moreover, 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA), indicators of oxidative stress, were also significantly inhibited after Alda-1 administration, which was accompanied by increased ALDH2 activity and protein expression.Conclusion Alda-1 improves cardiac and neurological dysfunction postresuscitation in a swine model of CA, at least partly by inhibiting oxidative stress-mediated NLRP3 inflammasome activation and pyroptosis.

Aims Many studies have indicated that microRNAs are closely related to the process of peripheral arterial disease (PAD). Previously, we found that microRNA-125a-3p (miR-125a-3p) in restenotic arteries after interventional therapy of lower extremity vessels was notably decreased compared with that of normal control arteries. However, its role in the development of vascular stenosis is not yet clearly understood. The purpose of this study was to investigate the expression, regulatory mechanism and function of miR-125a-3p in the process of vascular stenosis. Methods and results Quantitative reverse-transcription polymerase chain reaction assays indicated that miR-125a-3p in restenotic arteries after interventional therapy was significantly lower than that in normal control arteries. Immunofluorescence and in situ hybridization co-staining assays in arterial sections demonstrated that miR-125a-3p was mainly expressed in the medial smooth muscle layer. Transfection of miR-125a-3p mimics into cultured vascular smooth muscle cells (VSMCs) effectively inhibited cell proliferation and migration. Then, western blot and luciferase activity assays showed that recombinant human mitogen-activated protein kinase 1 (MAPK1) was a functional target of miR-125a-3p and was involved in miR-125a-3p-mediated cell effects. Finally, the lentiviral infection of miR-125a-3p in balloon-injured rat carotid vascular walls showed that miR-125a-3p overexpression significantly reduced the probability of neointimal membrane production. Conclusions miR-125a-3p can effectively inhibit the function of VSMCs and the occurrence of vascular stenosis by targeting MAPK1. This study introduces a new molecular mechanism of PAD. We show that regulation of the miR-125a-3p level has the potential to provide a new treatment for PAD and other proliferative vascular diseases.

Introduction: This study aimed to characterize antimicrobial resistance (AMR), molecular determinants of AMR and virulence, as well as clonal relationship of Streptococcus agalactiae isolates from women at 35-37 weeks of gestation in the Chaoshan metropolitan area of southern China. Methodology: Bacterial strains isolated from vaginal swabs were identified and antimicrobial susceptibility tests were performed by using a Vitek 2 Compact system (BioMérieux, France). Resistance and virulence genes were detected by polymerase chain reaction (PCR) and the clonal relationship was analysed by multiple locus variable number tandem repeat analysis (MLVA). Statistical analysis was carried out by using SPSS software, version 19.0. Results: All GBS were susceptible to benzylpenicillin, ampicillin, quinupristin/dalfopristin, tigecycline, linezolid and vancomycin, but a considerable proportion was resistant to clindamycin (29.67%), erythromycin (46.15%)， azithromycin (63.74%), tetracycline (84.62%) and quinolones (25.27%). The carrier rates of ermB (69.04%) and mefA/E (64.28%) were detected in these GBS strains resistant to erythromycin. In terms of MLVA detection, 91 GBS strains were categorized into 43 genotypes and 6 clusters. All GBS harboured hylB and cylE genes, most of which carried a combination of PI-1 and PI-2a genes as a common virulence gene profile. Conclusions: The high level of resistance conferred by some corresponding resistance genes to macrolides, lincosamides and quinolones of GBS isolates from pregnant women in southern China, has reinforced the necessity for monitoring GBS strain resistance to the above agents. Comparative genetic studies of GBS isolates, especially efforts to understand the relationship between pilus islands and genotype, were essential for conducting infection control and epidemiological comparisons between countries.

Aortic balloon occlusion (ABO) facilitates the success of cardiopulmonary resuscitation (CPR) in non-traumatic cardiac arrest, and is also effective in controlling traumatic hemorrhage; however, a prolonged occlusion results in irreversible organ injury and death. In this study, we investigated the effects of ABO on CPR outcomes and its optimal duration for post-resuscitation organ protection in a porcine model of traumatic cardiac arrest (TCA).Twenty-seven male domestic pigs weighing 33 ± 4 kg were utilized. Forty percent of estimated blood volume was removed within 20 min. The animals were then subjected to 5 min of untreated ventricular fibrillation and 5 min of CPR. Coincident with the start of CPR, the animals were randomized to receive either 30-min ABO (n = 7), 60-min ABO (n = 8) or control (n = 12). Meanwhile, fluid resuscitation was initiated by the infusion of normal saline with 1.5 times of hemorrhage volume in 1 h, and finished by the reinfusion of 50% of the shed blood in another 1 h. The resuscitated animals were monitored for 6 h and observed for an additional 18 h.During CPR, coronary perfusion pressure was significantly increased followed by a higher rate of resuscitation success in the 30 and 60-min ABO groups compared with the control group. However, post-resuscitation cardiac, neurologic dysfunction, and injuries were significantly milder accompanied with less renal and intestinal injuries in the 30-min ABO group than in the other two groups.In conclusion, ABO augmented the efficacy of CPR after TCA, and furthermore a 30-min ABO improved post-resuscitation cardiac and neurologic outcomes without exacerbating the injuries of kidney and intestine.

SOCS5 is a member of the suppressor of cytokine signaling (SOCS) protein family with important yet incompletely understood biological functions in cancer. In hepatocellular carcinoma (HCC), controversial tumor-promoting and tumor-suppressive roles of SOCS5 have been reported. Our study aims to unravel novel functions of SOCS5 in HCC, especially that affecting metastasis. We examined the expression levels of SOCS5 in HCC using publicly available datasets, and in our patient cohort, using quantitative real-time PCR, western blotting, and immunohistochemistry. The association of SOCS5 expression with clinical pathological data of HCC patients was examined and that with the mTOR pathway was predicted. We further studied the effects of SOCS5 on PI3K/Akt/mTOR activity; HCC cell autophagy, migration, and invasion; and HCC cell metastasis in vitro and in vivo. We observed that SOCS5 was significantly overexpressed in HCC tissues, compared to adjacent non-tumor liver tissues, in both the public datasets and in our patient cohort. SOCS5 overexpression was significantly and inversely correlated with HCC patient prognosis. Moreover, SOCS5 overexpression promoted HCC cell migration and invasion in vitro by inactivating PI3K/Akt/mTOR-mediated autophagy. Conversely, SOCS5 inhibition suppressed HCC cell migration and invasion in vitro by activating PI3K/Akt/mTOR-mediated autophagy. Dual inhibition of SOCS5 and mTOR further enhanced autophagy and the subsequent anti-metastatic effects on HCC cells. In vivo, stable knockdown of SOCS5 reduced HCC cell metastasis. Overall, our study revealed a novel metastasis-promoting function of SOCS5 in HCC, acting via the PI3K/Akt/mTOR-mediated autophagy pathway. Combined inhibition of SOCS5 and mTOR may be a potential therapeutic approach to inhibit HCC metastasis and prolong patient survival.

Cancer stem cells contribute to cancer progression, but the mechanisms underlying neuroblastoma stem cell development are unclear. Here, we examined the roles of the transcription factor SLC34A2 in regulating the stemness of neuroblastoma cells. We found that SLC34A2 expression was negatively correlated with the overall survival and relapse‐free survival probability of neuroblastoma patients. Additionally, SLC34A2 expression was observed to be remarkably increased in spheroids derived from neuroblastoma cells. Knockdown of SLC34A2 attenuated the expression of stemness markers and spheroid formation capacity of neuroblastoma cell‐derived spheroids, and overexpression of SLC34A2 exerted the opposite effects in neuroblastoma cells. Mechanistically, SLC34A2 was found to directly bind to the promoter of MIR25, which targets glycogen synthesis kinase 3β (Gsk3β), an antagonist of Wnt signaling. Transfection of miR‐25 inhibitor or a Gsk3β overexpression plasmid attenuated the effects of SLC34A2 overexpression on the stemness of neuroblastoma cells. Our results demonstrate that miR‐25/Gsk3β‐mediated activation of Wnt signaling is responsible for SLC34A2‐induced enhancement of neuroblastoma cell stemness.

Objectives As a noninvasive method for evaluation of cerebral hemodynamics, the correct interpretation of transcranial Doppler or transcranial imaging (TCI) data remains a major challenge. We explored how to interpret the pulsatility index (PI) derived via TCI during evaluations of cerebral hemodynamics in posthemicraniectomy patients. Methods We included patients who underwent invasive arterial pressure and intracranial pressure (ICP) monitoring and simultaneous TCI examinations after hemicraniectomy. We classified the PI of the middle cerebral artery (MCA) into ipsilateral (craniectomy side) and contralateral (opposite side) and analyzed both data sets. The statistical analysis was performed by the Bland‐Altman approach, by calculating intraclass correlation coefficients and Spearman correlations, and by drawing receiver operating characteristic curves. Pulsatility index probability charts were created for ICPs exceeding 20, 25, and 30 mm Hg and cerebral perfusion pressures (CPPs) lower than 70, 60, and 50 mm Hg; we thus explored defined ICP and CPP values. Results The ipsilateral and contralateral MCA PI data differed. Only the ipsilateral MCA PI showed a weak correlation with ICP (r = 0.378; P

Xylan is one of the main anti-nutritional factors in pig’s feed. Although supplementation of β-xylanase in diet can improve the utilization of nutrients in animals, it is limited by feed cost, manufacturing process and storage stability. To determine whether the expression of endogenous β-xylanase gene xynB in vivo can improve digestibility of dietary xylan and absorption of nutrients, we produced transgenic pigs which express the xynB from Aspergillus Niger CGMCC1067 in the parotid gland via nuclear transfer. In four live transgenic founders, β-xylanase activities in the saliva were 0.74, 0.59, 0.37 and 0.24 U/mL, respectively. Compared with non-transgenic pigs, the content of crude protein (CP) in feces reduced by 15.5% (P

Background: High-flow nasal cannula (HFNC) oxygen therapy has been shown to reduce the need for mechanical ventilation and decrease the duration of hospital and intensive care unit (ICU) stays for patients with a severely compromised respiratory system. This study aims to observe the evolution of lung aeration via lung ultrasound score (LUS) in a chest-injured population who had been treated with HFNC oxygen therapy, and to assess the benefit of the HFNC oxygen therapy in trauma patients. Methods: A retrospective study examined trauma patients with moderate to severe thoracic injuries who were admitted to the ICU at a tertiary hospital between October 2015 and March 2017. The decision to initiate HFNC oxygen therapy was made at the discretion of the trauma surgeon and respiratory therapist when supplemental oxygen delivery was required. All of the patients were assessed by transthoracic lung ultrasound every day after being admitted into the ICU. We retrospectively analyzed 3 time points for this study: the initial emergency intensive care units presentation within 12 hours (T1), 24 to 48 hours after the treatment (T2), and 72 to 96 hours after the treatment (T3). Transthoracic lung ultrasound was performed by an experienced investigator with level 3 certification using a Mindray M9 echograph and a 2- to 4-MHz round-tipped probe. Primary outcomes were the need for intubation after HFNC oxygen therapy for respiratory failure during the treatment within 72 hours, the length of ICU stay, and mortality of 28 days. Results: During the study period, 50 patients with blunt chest trauma were admitted to the study; 18 patients received HFNC therapy and 32 received conventional oxygen therapy (COT); there was no significant difference in the baseline clinical characteristics between the 2 groups. The length of ICU stay and intubation rate for respiratory failure within 72 hours were significantly different between the 2 groups ( P < .05), but there was no difference in the 28-day mortality. The LUS of the COT group was not significantly different from T1 to T2 or from T2 to T3 ( P > .05). However, the LUS decreased significantly—by 25% from T1 to T2 ( P < .05) and by 31% from T1 to T3 ( P < .05) in the HFNC therapy group. The LUS of the patients intubated for respiratory failure within 72 hours, in the COT group increased from T1 (17 ± 3) to T3 (21 ± 3), and the LUS (21 ± 3) was much higher than the patients who were not intubated (11 ± 3) at T3; the LUS of the HFNC group was all above 15, which was not significantly different from T1 to T2 or from T2 to T3 ( P > .05). Conclusions: High-flow nasal cannula oxygen therapy may be considered as an initial respiratory therapy for trauma patients with blunt chest injury. High-flow nasal cannula therapy could improve lung aeration as noted by the transthoracic lung ultrasound assessment, and LUS may help the attending physicians identify the usefulness of HFNC therapy and decide whether to continue the use of HFNC therapy or intubate the patient.

The advent of induced pluripotent stem cells (iPSCs) and identification of transcription factors for cardiac reprogramming have raised hope to cure heart disease, the leading cause of death in the world. Our knowledge in heart development and molecular barriers of cardiac reprogramming is advancing, but many hurdles are yet to be overcome for clinical translation. Importantly, we lack a full understanding of molecular mechanisms governing cell fate conversion toward cardiomyocytes. In this review, we will discuss the role of metabolism in directed differentiation versus trans-differentiation of cardiomyocytes. Cardiomyocytes exhibit a unique metabolic feature distinct from PSCs and cardiac fibroblasts, and there are multiple overlapping molecular mechanisms underlying metabolic reprogramming during cardiomyogenesis. We will discuss key metabolic changes occurring during cardiomyocytes differentiation from PSCs and cardiac fibroblasts, and the potential role of metabolic reprogramming in the enhancement strategies for cardiomyogenesis. Only when such details are discovered will more effective strategies to enhance the de novo production of cardiomyocytes be possible.

Background We investigated the effectiveness of automated pupillometry on monitoring cardiopulmonary resuscitation (CPR) and predicting return of spontaneous circulation (ROSC) in a swine model of cardiac arrest (CA). Methods Sixteen male domestic pigs were included. Traditional indices including coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO2), regional cerebral tissue oxygen saturation (rSO2) and carotid blood flow (CBF) were continuously monitored throughout the experiment. In addition, the pupillary parameters including the initial pupil size before constriction (Init, maximum diameter), the end pupil size at peak constriction (End, minimum diameter), and percentage of change (%PLR) were measured by an automated quantitative pupillometer at baseline, at 1, 4, 7 min during CA, and at 1, 4, 7 min during CPR. Results ROSC was achieved in 11/16 animals. The levels of CPP, ETCO2, rSO2 and CBF were significantly greater during CPR in resuscitated animals than those non-resuscitated ones. Init and End were decreased and %PLR was increased during CPR in resuscitated animals when compared with those non-resuscitated ones. There were moderate to good significant correlations between traditional indices and Init, End, and %PLR (|r| = 0.46–0.78, all P Conclusion The automated pupillometry may serve as an effective surrogate method to monitor cardiopulmonary resuscitation efficacy and predict ROSC in a swine model of cardiac arrest.

The role of autophagic mechanisms in the protective effect of berberine (BBR) on lipopolysaccharide (LPS)-induced injury in the endothelial cells human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) was investigated. Cell viability, proliferation, and apoptosis were detected by the CCK-8 assay, the EdU kit, and flow cytometry, respectively, and autophagy-related protein expression, the number of autophagic vacuoles, and LC3 double-fluorescence were examined using western blot analysis, transmission electron microscopy, and confocal microscopy, respectively. LPS resulted in a decrease in the cell viability and proliferation of HUVECs and HPMECs and an increase in the number of apoptotic cells, while BBR treatment resulted in an increase in cell viability and proliferation, as well as a decrease in cell apoptosis. Furthermore, BBR could inhibit LPS-induced autophagy, as demonstrated by its inhibitory effects on the LC3-II/LC3-I ratio and Beclin-1 levels and its promotive effect on p62 expression. Addition of the autophagy inducer rapamycin (RAPA) aggravated LPS-induced injury, while treatment with the autophagy blocker 3-methyladenine (3-MA) attenuated the injury. Further, the protective effect of BBR was inhibited by rapamycin. JNK inhibition by SP600125 inhibited LPS-induced autophagy, and BBR could not alter the LPS-induced autophagy in HUVECs and HPMECs that were pretreated with SP600125. The present data indicate that BBR attenuated LPS-induced cell apoptosis by blocking JNK-mediated autophagy in HUVECs and HPMECs. Therefore, the JNK-mediated autophagy pathway could be a potential target for the prevention and treatment of cardiovascular disease., GRAPHICAL ABSTRACT

Evaluation of potential vascular injury is an essential part of the safety study during pharmaceutical development. Vascular liability issues are important causes of drug termination during preclinical investigations. Currently, preclinical assessment of vascular toxicity primarily relies on the use of animal models. However, accumulating evidence indicates a significant discrepancy between animal toxicity and human toxicity, casting doubt on the clinical relevance of animal models for such safety studies. While the causes of this discrepancy are expected to be multifactorial, species differences are likely a key factor. Consequently, a human-based model is a desirable solution to this problem, which has been made possible by the advent of human induced pluripotent stem cells (iPSCs). In particular, recent advances in the field now allow the efficient generation of a variety of vascular cells (e.g., endothelial cells, smooth muscle cells, and pericytes) from iPSCs. Using these cells, different vascular models have been established, ranging from simple 2D cultures to highly sophisticated vascular organoids and microfluidic devices. Toxicity testing using these models can recapitulate key aspects of vascular pathology on molecular (e.g., secretion of proinflammatory cytokines), cellular (e.g., cell apoptosis), and in some cases, tissue (e.g., endothelium barrier dysfunction) levels. These encouraging data provide the rationale for continuing efforts in the exploration, optimization, and validation of the iPSC technology in vascular toxicology.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) can timely prevent the wounded from fatal hemorrhage. However, blind insertion of REBOA in field or emergency room may result in catheter malposition and serious complications. We aim to develop a new method based on surface landmarks to guide the accurate placement of REBOA in zone III of aorta without fluoroscopy. A retrospective study was conducted in a university hospital, including 57 subjects who underwent computed tomography angiography (CTA) from April to December in 2019. External distances and intravascular lengths were measured by three-dimensional reconstruction of CT images, including the distances from the insertion site of femoral artery to the xiphoid process (FA-Xi), the midpoint between the xiphoid process and the umbilicus (FA-mXU), the umbilicus (FA-Ui), the midpoint of the zone III of aorta (FA-mZIII), the lowest renal artery (FA-LRA), and aortic bifurcation (FA-AB). The distal and proximal ideal margin and predicted accuracy were calculated by curvature plane reconstruction. The predicted probability of balloon positioning in zone III by different methods was compared. The mean age of all patients was 60 years (SD = 9.4). The average length of zone III of aorta was 9.4 cm (SD = 1.0), and the length of FA-mZIII on the right and left sides were 24.4 cm (SD = 2.1), 23.8 cm (SD = 2.1), respectively. FA-Xi was longer than FA-LRA, and FA-Ui was shorter than FA-AB (paired two-tailed test, p

Purpose: To investigate the clinical effectiveness of a pneumatic compression device (PCD) combined with low-molecular-weight heparin (LMWH) for the prevention and treatment of deep vein thrombosis (DVT) in trauma patients.Materials and Methods: This study retrospectively analyzed 286 patients with mild craniocerebral injury and clavicular fractures admitted to our department from January 2016 to February 2020. Patients treated with only LMWH were used as the control group, and patients treated with a PCD combined with LMWH were used as the observation group. The incidence of DVT, the postoperative change in the visual analog scale (VAS) score and coagulation function were observed and compared between the two groups. Excluding the influence of other single factors, binary logistic regression analysis can indicate whether the use of a PCD effectively improves the patient's postoperative coagulation function.Result: The incidence of DVT in the observation group was significantly lower than that in the control group (7.1% vs. 16.7%, respectively, χ2=4.605, P0.05). According to binary logistic regression analysis, the postoperative risk of DVT in patients with LMWH alone was 1.764 times that with the combination of LMWH+PCD (P Conclusion: Compared with LMWH alone, PCD combined with LMWH can improve blood rheology and coagulation function in patients with traumatic brain injury and clavicular fracture, significantly reduce the incidence of DVT, shorten the hospital stay and improve the clinical effectiveness of treatment.

Receptor interacting serine/threonine kinase 4 (RIPK4) is a member of the threonine/serine protein kinase family; it plays related functions in a variety of tumours, but its biological function has not been fully revealed. It has been reported that it is differentially expressed in hepatocellular carcinoma (HCC). Our research aimed to reveal the role of RIPK4 in the progression of HCC and to reveal the biological behaviour of RIPK4 in HCC. We analysed the differences in RIPK4 expression in HCC by using a publicly available data set. By using PCR, Western blotting and immunohistochemical staining methods, we detected the expression level of RIPK4 in HCC patient specimens and studied the relationship between the expression of RIPK4 and the clinicopathological features of HCC patients. The prognostic data were combined to analyse the relationship between RIPK4 and HCC patient survival and tumour recurrence. We found that the expression level of RIPK4 in nontumour tissues was significantly higher than that in tumour tissues, and the level of RIPK4 was significantly positively correlated with postoperative survival and recurrence in HCC patients. Further, our study found that RIPK4 inhibits the progression of HCC by influencing the invasion and metastasis of HCC and that overexpression of RIPK4 reduces the invasion and metastasis of HCC by inhibiting epithelial-mesenchymal transition (EMT) and the STAT3 pathway. In in vivo experiments, overexpression of RIPK4 stably inhibited HCC metastasis. To summarize, our research revealed the relationship between RIPK4 and the prognosis of patients with HCC. We discovered that RIPK4 affects the invasion and metastasis of HCC through the EMT and STAT3 pathways. Targeted inhibition of the RIPK4 gene and the STAT3 pathway may be potential therapeutic strategies for inhibiting the postoperative recurrence and metastasis of HCC.

Traditional Chinese medicine has shown great safety and efficacy in the treatment of heart failure (HF), whereas the mechanism remains unclear. In this study, the protective effect of Yixin-shu (YXS) capsules, a conventional medicine for various cardiovascular diseases, against myocardial ischemia-induced HF in rats was systematically investigated by RNA-seq technology. HF rats treated with YXS (0.8 or 1.6 g/kg/d, ig) for 6 weeks had significantly decreased brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and collagen III and attenuated cardiac structure rupture and collagen deposition. Additionally, YXS treatment decreased the levels of interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and lactate dehydrogenase (LDH) and TUNEL-positive rate and the nitrotyrosine staining, but increased levels of glutathione (GSH), total antioxidant capacity (T-AOC) activity, and mitochondrial membrane potential. Further experiments demonstrated that YXS restored Trx2 and inhibited the phosphorylation of JNK and p38, thereby improving cardiac function in the rats with HF. Silencing Trx2 decreased the protection of YXS in the response to H2O2 as evidenced by the increase of caspase-3 activity and decrease of GSH level. Thus, YXS enhanced heart function and decreased myocardial damage through restoring Trx2 and inhibiting JNK and p38 activation in ischemia-induced HF.

Background: Health system planning requires careful assessment of accidental carbon monoxide poisoning (ACOP) epidemiology, but data of this disease are scarce or non-existent in many countries. This article investigates the global burden of ACOP based on the Global Burden of Disease Study 2019 (GBD 2019) and the World Bank database. Methods: Numbers and age-standardized rates (ASR) of ACOP incidence, prevalence, deaths, Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLDs), and Years of Life Lost (YLLs) were analyzed at global, regional, and national level. The estimated annual percentage change (EAPC) of age-standardized rates (ASR) was calculated by generalizing the linear model with a Gaussian distribution. The carbon monoxide index (ICO) was generated to describe the changes in the national medical development. Ages, sexes, and economics parameters are included to access their internal relevance. Findings: Globally, in 2019, there were approximately 0·97 million ACOP incidence cases (95% CI 0·66 million to 1·4 million), and 41,142 (95%UI 32957 to 45934) people died from it. The age-standardized rate of incidence (ASIR) and age-standardized rate of deaths (ASDR) are 13·05 per 100,000 population (8·84 to 18·69) and 0·52 per 100,000 population (95%UI 0·41 to 0·58) respectively. Compared with 1990, the morbidity and mortality of ACOP in 2019 are on a downward trend. The EAPC of two parameters are -0·53 (-0·67 to -0·4) and -1·95 (-2·26 to -1·64). East Europe and Central Europe are the areas where the ASIR and ASDR of ACOP have decreased most significantly. By sexes, from 1990 to 2019, females have a higher ASIR than males, but whether it is analyzed from region or age, females have lower ASDR than males. In 2019, the countries with lower SDI have a lower ACOP morbidity, but a higher mortality. This article also finds that the relevant parameters of ACOP are closely related to the economic parameters. This correlation enables us to evaluate the level and status of public health services in various countries. Interpretation: ACOP is the most common toxic disease in the world. In 2019, the number of patients who die from ACOP exceeded that of patients poisoned by all other means. With the development of technology, infrastructure and related policies, ACOP can be effectively prevented and treated to a large extent. In global health decision-making, especially in regions with high-middle and high SDI, more attention should be paid. Funding Statement: Not applicable. Declaration of Interests: The authors have declared that they have no competing interests.