The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.

Cardiac arrest, stony heart, and cardiopulmonary resuscitation: An updated revisit

The post-resuscitation period is recognized as the main predictor of cardiopul-monary resuscitation(CPR)outcomes.The first description of post-resuscitation syndrome and stony heart was published over 50 years ago.Major manifestations may include but are not limited to,persistent precipitating pathology,systemic ischemia/reperfusion response,post-cardiac arrest brain injury,and finally,post-cardiac arrest myocardial dysfunction(PAMD)after successful resuscitation.Why do some patients initially survive successful resuscitation,and others do not?Also,why does the myocardium response vary after resuscitation?These ques-tions have kept scientists busy for several decades since the first successful resuscitation was described.By modifying the conventional modalities of resu-scitation together with new promising agents,rescuers will be able to salvage the jeopardized post-resuscitation myocardium and prevent its progression to a dismal,stony heart.Community awareness and staff education are crucial for shortening the resuscitation time and improving short-and long-term outcomes.Awareness of these components before and early after the restoration of circulation will enhance the resuscitation outcomes.This review extensively addresses the underlying pathophysiology,management,and outcomes of post-resuscitation syndrome.The pattern,management,and outcome of PAMD and post-cardiac arrest shock are different based on many factors,including in-hospital cardiac arrest vs out-of-hospital cardiac arrest(OHCA),witnessed vs unwitnessed cardiac arrest,the underlying cause of arrest,the duration,and protocol used for CPR.Although restoring spontaneous circulation is a vital sign,it should not be the end of the game or lone primary outcome;it calls for better understanding and aggressive multi-disciplinary interventions and care.The development of stony heart post-CPR and OHCA remain the main challenges in emergency and critical care medicine.

Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest:a prospective single-center observational study

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were calculated.The Cerebral Performance Category(CPC) score was recorded on day 28 after ROSC.RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested.CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive eflcacy of LDH during the first week was superior to others.

From mice to humans:a need for comparable results in mammalian neuroplasticity

Brain plasticity-A universal tool with many variations:The study of brain plasticity has been gaining interest since almost a century and has now reached a huge amount of information(>80,000 results in PubMed).Overall,different types of plasticity,including stem cell-driven genesis of new neurons(adult neurogenesis),cells in arrested maturation(dormant neurons),neuro-glial and synaptic plasticity,can coexist and contribute to grant plastic changes in the brain,from a cellular to system level(Benedetti and Couillard-Despres,2022;Bonfanti et al.,2023).

Critical Solvation Structures Arrested Active Molecules for Reversible Zn Electrochemistry

Aqueous Zn-ion batteries(AZIBs)have attracted increasing attention in next-generation energy storage systems due to their high safety and economic.Unfortunately,the side reactions,dendrites and hydrogen evolution effects at the zinc anode interface in aqueous electrolytes seriously hinder the application of aqueous zinc-ion batteries.Here,we report a critical solvation strategy to achieve reversible zinc electrochemistry by introducing a small polar molecule acetonitrile to form a“catcher”to arrest active molecules(bound water molecules).The stable solvation structure of[Zn(H_(2)O)_(6)]^(2+)is capable of maintaining and completely inhibiting free water molecules.When[Zn(H_(2)O)_(6)]^(2+)is partially desolvated in the Helmholtz outer layer,the separated active molecules will be arrested by the“catcher”formed by the strong hydrogen bond N-H bond,ensuring the stable desolvation of Zn^(2+).The Zn||Zn symmetric battery can stably cycle for 2250 h at 1 mAh cm^(-2),Zn||V_(6)O_(13) full battery achieved a capacity retention rate of 99.2%after 10,000 cycles at 10 A g^(-1).This paper proposes a novel critical solvation strategy that paves the route for the construction of high-performance AZIBs.

Hydrangea serrata extract exerts tumor inhibitory activity against hepatocellular carcinoma HepG2 cells via inducing p27/CDK2-mediated cell cycle arrest and apoptosis

Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.

A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study

BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest patients.This study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysmogram(POP)parameters can be used to identify unsustained ROSC.METHODS:We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to 2014.Patients’general information,ETCO_(2),and POP parameters were collected and statistically analyzed.RESULTS:The included 105 ROSC episodes(from 80 cardiac arrest patients)comprised 51 sustained ROSC episodes and 54 unsustained ROSC episodes.The 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group(29.2%vs.9.4%,P<0.05).The logistic regression analysis showed that the difference between after and before ROSC in ETCO_(2)(ΔETCO_(2))and the difference between after and before ROCS in area under the curve of POP(ΔAUCp)were independently associated with sustained ROSC(odds ratio[OR]=0.931,95%confi dence interval[95%CI]0.881-0.984,P=0.011 and OR=0.998,95%CI 0.997-0.999,P<0.001).The area under the receiver operating characteristic curve ofΔETCO_(2),ΔAUCp,and the combination of both to predict unsustained ROSC were 0.752(95%CI 0.660-0.844),0.883(95%CI 0.818-0.948),and 0.902(95%CI 0.842-0.962),respectively.CONCLUSION:Patients with unsustained ROSC have a poor prognosis.The combination ofΔETCO_(2) andΔAUCp showed signifi cant predictive value for unsustained ROSC.

Simple bone cysts of the proximal humerus presented with limb length discrepancy:A case report

BACKGROUND Simple bone cysts(SBC)are benign tumor-like bone lesions typically identified in children.While SBC may lead to growth disturbances or growth arrest,such cases are uncommon.The mechanisms behind these observations remain unclear.Additionally,research on the etiology of SBC remains inconclusive,and there has been no consensus on the appropriate timing and methodology for treatment.CASE SUMMARY Here,we present our experience in the successful surgical management of a 10-year-old girl with SBC,who presented with a pathological fracture complicated by malunion of the displaced fracture,varus deformity,and limb length discrepancy.We hypothesized two possible etiologies for the patient’s growth arrest and subsequent humerus varus deformity:(1)Direct disruption of the physis by fluid from the cyst itself;and(2)damage to the epiphysis due to repetitive pathological fractures associated with SBC.In addressing this case,surgical intervention was undertaken to correct the proximal humerus varus deformity.This approach offered the advantages of simultaneously correcting angular abnormalities,achieving mild limb lengthening,providing definitive SBC treatment,and reducing the overall treatment duration.CONCLUSION As per current literature,acute correction of acute angular deformity in proximal humeral SBC is not well comprehended.However,in this specific case,acute correction was considered an optimal solution.

Approach to traumatic cardiac arrest in the emergency department: a narrative literature review for emergency providers

BACKGROUND:Traumatic cardiac arrest(TCA)is a major contributor to mortality and morbidity in all age groups and poses a significant burden on the healthcare system.Although there have been advances in treatment modalities,survival rates for TCA patients remain low.This narrative literature review critically examines the indications and eff ectiveness of current therapeutic approaches in treating TCA.METHODS:We performed a literature search in the PubMed and Scopus databases for studies published before December 31,2022.The search was refi ned by combining search terms,examining relevant study references,and restricting publications to the English language.Following the search,943 articles were retrieved,and two independent reviewers conducted a screening process.RESULTS:A review of various studies on pre-and intra-arrest prognostic factors showed that survival rates were higher when patients had an initial shockable rhythm.There were conflicting results regarding other prognostic factors,such as witnessed arrest,bystander cardiopulmonary resuscitation(CPR),and the use of prehospital or in-hospital epinephrine.Emergency thoracotomy was found to result in more favorable outcomes in cases of penetrating trauma than in those with blunt trauma.Resuscitative endovascular balloon occlusion of the aorta(REBOA)provides an advantage to emergency thoracotomy in terms of occupational safety for the operator as an alternative in managing hemorrhagic shock.When implemented in the setting of aortic occlusion,emergency thoracotomy and REBOA resulted in comparable mortality rates.Veno-venous extracorporeal life support(V-V ECLS)and veno-arterial extracorporeal life support(V-A ECLS)are viable options for treating respiratory failure and cardiogenic shock,respectively.In the context of traumatic injuries,V-V ECLS has been associated with higher rates of survival to discharge than V-A ECLS.CONCLUSION:TCA remains a signifi cant challenge for emergency medical services due to its high morbidity and mortality rates.Pre-and intra-arrest prognostic factors can help identify patients who are likely to benefit from aggressive and resource-intensive resuscitation measures.Further research is needed to enhance guidelines for the clinical use of established and emerging therapeutic approaches that can help optimize treatment effi cacy and ameliorate survival outcomes.

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

Recovering from prolonged cardiac arrest induced by electric shock:A case report

BACKGROUND Cardiac arrest(CA)induced by electric shock is a rare occurrence,particularly in cases of prolonged CA.Currently,there is limited literature on similar incidents,and we present a relevant case report.CASE SUMMARY A 27-year-old Asian male man,experiencing respiratory CA due to electric shock,was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions.In the subsequent stages,the patient received multiple organ function protection measures,leading to a successful recovery and eventual discharge from the hospital.CONCLUSION Prolonging resuscitation time can enhance the chances of survival for patients,this study provide valuable insights into the management of electric shock-induced CA.

Impact of depression on in-hospital outcomes for adults with type 2 myocardial infarction:A United States population-based analysis

BACKGROUND Type 2 myocardial infarction(T2MI)is an ischemic myocardial injury in the context of oxygen supply/demand mismatch in the absence of a primary coronary event.However,though there is a rising prevalence of depression and its potential association with type 1 myocardial infarction(T1MI),data remains nonexistent to evaluate the asso-ciation with T2MI.AIM To identify the prevalence and risk of T2MI in adults with depression and its impact on the in-hospital outcomes.METHODS We queried the National Inpatient Sample(2019)to identify T2MI hospitalizations using Internal Classification of Diseases-10 codes in hospitalized adults(≥18 years).In addition,we compared sociodemographic and comorbidities in the T2MI cohort with vs without comorbid depression.Finally,we used multivariate regression analysis to study the odds of T2MI hospitalizations with vs without depression and in-hospital outcomes(all-cause mortality,cardiogenic shock,cardiac arrest,and stroke),adjusting for confounders.Statistical significance was RESULTS There were 331145 adult T2MI hospitalizations after excluding T1MI(median age:73 years,52.8%male,69.9%white);41405(12.5%)had depression,the remainder;289740 did not have depression.Multivariate analysis revealed lower odds of T2MI in patients with depression vs without[adjusted odds ratio(aOR)=0.88,95%confidence interval(CI):0.86-0.90,P=0.001].There was the equal prevalence of prior MI with any revascularization and a similar prevalence of peripheral vascular disease in the cohorts with depression vs without depression.There is a greater prevalence of stroke in patients with depression(10.1%)vs those without(8.6%).There was a slightly higher prevalence of hyperlipidemia in patients with depression vs without depression(56.5%vs 48.9%),as well as obesity(21.3%vs 17.9%).There was generally equal prevalence of hypertension and type 2 diabetes mellitus in both cohorts.There was no significant difference in elective and non-elective admissions frequency between cohorts.Patients with depression vs without depression also showed a lower risk of all-cause mortality(aOR=0.75,95%CI:0.67-0.83,P=0.001),cardiogenic shock(aOR=0.65,95%CI:0.56-0.76,P=0.001),cardiac arrest(aOR=0.77,95%CI:0.67-0.89,P=0.001)as well as stroke(aOR=0.79,95%CI:0.70-0.89,P=0.001).CONCLUSION This study revealed a significantly lower risk of T2MI in patients with depression compared to patients without depression by decreasing adverse in-hospital outcomes such as all-cause mortality,cardiogenic shock,cardiac arrest,and stroke in patients with depression.

Correction:Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest

This is an erratum to an already published paper named“Establishment of a prediction model for prehospital return of spontaneous circulation in out-ofhospital patients with cardiac arrest”.We found errors in the affiliated institution of the authors.We apologize for our unintentional mistake.Please note,these changes do not affect our results.

The Role of Age as a Risk Factor for Pickleball-Related Injuries

Pickleball is a popular sport that includes players from many different demographics. The popularity has resulted in not only increases in participation but also in activity related injuries. The purpose of this study was to identify risk factors along with potential mechanisms for injuries related to pickleball and identify effective countermeasures. Methods included the identification of pickleball related injuries from a US National Emergency Room database (NEISS). A narrative section of the database was used to identify and categorize potential mechanisms of injury. Results indicated that the types and mechanisms of injury relate to three specific age groups: younger, middle age, and older players. Injuries to younger players under the age of 26 are likely the result of misuse of sport equipment. Middle aged players from 26 to 50 sustained injuries more related activity overuse. However, there were more concerns with players over 50 years of age with a great percentage resulting in cardia arrest or symptoms leading to more severe cardiovascular conditions. While pickleball activity should be encouraged as it is a beneficial form of physical activity, there should be specific age-group interventions to reduce injury. It should be highly recommended that doctors approve the activity for individual at risk for heart conditions and supervision for adults in that age group.

In-hospital outcomes in COVID-19 patients with non-alcoholic fatty liver disease by severity of obesity:Insights from national inpatient sample 2020

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular diseases independently of other risk factors.However,data on its effect on cardiovascular outcomes in coronavirus disease 2019(COVID-19)hospitalizations with varied obesity levels is scarce.Clinical management and patient care depend on understanding COVID-19 admission results in NAFLD patients with varying obesity levels.AIM To study the in-hospital outcomes in COVID-19 patients with NAFLD by severity of obesity.METHODS COVID-19 hospitalizations with NAFLD were identified using International Classification of Disease-10 CM codes in the 2020 National Inpatient Sample database.Overweight and Obesity Classes Ⅰ,Ⅱ,and Ⅲ(body mass index 30-40)were compared.Major adverse cardiac and cerebrovascular events(MACCE)(all-cause mortality,acute myocardial infarction,cardiac arrest,and stroke)were compared between groups.Multivariable regression analyses adjusted for sociodemographic,hospitalization features,and comorbidities.RESULTS Our analysis comprised 13260 hospitalizations,7.3% of which were overweight,24.3% Class Ⅰ,24.1% Class Ⅱ,and 44.3% Class Ⅲ.Class Ⅲ obesity includes younger patients,blacks,females,diabetics,and hypertensive patients.On multivariable logistic analysis,Class Ⅲ obese patients had higher risks of MACCE,inpatient mortality,and respiratory failure than Class Ⅰ obese patients.Class Ⅱ obesity showed increased risks of MACCE,inpatient mortality,and respiratory failure than Class I,but not significantly.All obesity classes had non-significant risks of MACCE,inpatient mortality,and respiratory failure compared to the overweight group.CONCLUSION Class Ⅲ obese NAFLD COVID-19 patients had a greater risk of adverse outcomes than class Ⅰ.Using the overweight group as the reference,unfavorable outcomes were not significantly different.Morbid obesity had a greater risk of MACCE regardless of the referent group(overweight or Class Ⅰ obese)compared to overweight NAFLD patients admitted with COVID-19.

Flashover Probability of Wind Turbine Blade and Impact of Strong Electromagnetic Pulse from Lightning Strikes on Wind Turbine Safety

This paper systematically studies the flashover probability of wind turbine blade lightning arrester and the impact of strong electromagnetic pulses on the local and surrounding wind turbines during lightning strikes.The research results indicate that the flashover probability of direct lightning strikes by the wind turbine blade lightning arrester is almost negligible,and the strong electromagnetic pulse of wind turbine blade during lightning strikes has a serious impact on the electronic equipment of the machine,while the impact on the surrounding wind turbine is relatively small.At the same time,the calculation formula for the reflection of lightning current on the carbon brush between the wind turbine hub and the engine compartment during the flashing of the wind turbine blades is provided,and the calculation method for calculating the spatial gradient distribution of electromagnetic field intensity using Biot-Savart Law theorem is applied.The limitations of using wind turbine blades for lightning protection are pointed out,and a technical route for achieving wind turbine lightning safety is proposed,which can be used as a reference for wind turbine lightning protection technicians.

The neuro-prognostic value of the ion shift index in cardiac arrest patients following extracorporeal cardiopulmonary resuscitation

BACKGROUND:The ion shift index(ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic injury.We aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at hospital discharge in cardiac arrest(CA) patients following extracorporeal cardiopulmonary resuscitation(ECPR) and to compare its performance to other prognostic predictors.METHODS:This was a retrospective observational study including adult CA patients treated with ECPR between January 2018 and December 2022 in a tertiary hospital.Data regarding clinical characteristics and laboratory parameters were collected from medical records.The ISI was determined based on the first available serum electrolyte levels after ECPR.The primary outcome was unfavorable neurological status at hospital discharge,defined as Cerebral Performance Categories 3–5.Comparisons of the characteristics between the two groups were made using the χ2 test for categorical variables and the t-test or non-parametric Mann-Whitney U-test for continuous variables,as appropriate.Correlation analysis was performed using Spearman’s rank correlation coeficient.A two-tailed P-value <0.05 was considered statistically significant.RESULTS:Among the 122 patients involved,46(37.7%) had out-of-hospital CA,and 88 had unfavorable neurological outcomes.The ISI was significantly higher in the unfavorable outcome group than in the favorable outcome group(3.74 [3.15–4.57] vs.2.69 [2.51–3.07],P<0.001).A higher ISI level was independently related to unfavorable outcome(odds ratio=6.529,95% confidence interval 2.239–19.044,P=0.001).An ISI level >3.12 predicted unfavorable outcomes with a sensitivity and specificity of 74.6% and 85.2%,respectively(P<0.001).The prognostic performance of ISI(area under the curve [AUC]=0.887) was similar to that of other predictors,such as gray-to-white matter ratio(AUC=0.850,P=0.433) and neuronspecific enolase(AUC=0.925,P=0.394).CONCLUSION:ISI may be used as a prognostic biomarker to predict neurological outcomes in CA patients following ECPR.

5-methoxytryptophan induced apoptosis and PI3K/Akt/FoxO3a phosphorylation in colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a highly prevalent malignancy worldwide,and new therapeutic targets urgently need to be found to prolong patient survival.5-methoxytryptophan(5-MTP)is a tryptophan metabolite found in animals and humans.However,the effects of 5-MTP on proliferation and apoptosis of CRC cells are currently unknown.AIM To investigate the effects of 5-MTP on the proliferation,migration,invasion,and apoptosis abilities of CRC cells.Additionally,we seek to explore whether 5-MTP has the potential to be utilized as a drug for the treatment of CRC.METHODS In order to evaluate the effect of 5-MTP on CRC cells,a series of experiments were conducted for evaluation.Colony formation assay and Cell Counting Kit 8 assays were used to investigate the impact of 5-MTP on the proliferation of CRC cell lines.Cell cycle assays were employed to examine the effect of 5-MTP on cellular growth.In addition,we investigated the effects of 5-MTP on apoptosis and reactive oxygen species in HCT-116 cells.To obtain a deeper understanding of how 5-MTP affects CRC,we conducted a study to examine its influence on the PI3K/Akt signaling pathway in CRC cells.RESULTS This article showed that 5-MTP promoted apoptosis and cell cycle arrest and inhibited cell proliferation in CRC cells.In many articles,it has been reported that PI3K/Akt/FoxO3a signaling pathway is one of the most important signaling pathways involved in internal regulating cell proliferation and differentiation. Nevertheless, 5-MTP combined with PI3K/Akt/FoxO3a signaling pathway inhibitors significantly promotedapoptosis and cell cycle arrest and inhibited cell proliferation in CRC cells compared with 5-MTP alone in ourstudy.CONCLUSIONTherefore, there is strong evidence that 5-MTP can be used as an effective medicine for CRC treatment.

Establishment of a prediction model for prehospital return of spontaneous circulation in out-of-hospital patients with cardiac arrest

BACKGROUND Out-of-hospital cardiac arrest(OHCA)is a leading cause of death worldwide.AIM To explore factors influencing prehospital return of spontaneous circulation(P-ROSC)in patients with OHCA and develop a nomogram prediction model.METHODS Clinical data of patients with OHCA in Shenzhen,China,from January 2012 to December 2019 were retrospectively analyzed.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were applied to select the optimal factors predicting P-ROSC in patients with OHCA.A nomogram prediction model was established based on these influencing factors.Discrimination and calibration were assessed using receiver operating charac-teristic(ROC)and calibration curves.Decision curve analysis(DCA)was used to evaluate the model’s clinical utility.RESULTS Among the included 2685 patients with OHCA,the P-ROSC incidence was 5.8%.LASSO and multivariate logistic regression analyses showed that age,bystander cardiopulmonary resuscitation(CPR),initial rhythm,CPR duration,ventilation mode,and pathogenesis were independent factors influencing P-ROSC in these patients.The area under the ROC was 0.963.The calibration plot demonstrated that the predicted P-ROSC model was concordant with the actual P-ROSC.The good clinical usability of the prediction model was confirmed using DCA.CONCLUSION The nomogram prediction model could effectively predict the probability of P-ROSC in patients with OHCA.

Scopoletin: Anticancer potential and mechanism of action

Cancer is considered a leading cause of death worldwide due to its high morbidity and mortality rate.Conventional treatments for cancer therapy,such as chemotherapy,and radiotherapy,have been hampered by their side effects.Natural product-derived plants have been used for decades to treat diseases.Compared to conventional therapy,natural product has the potential to be effective against cancer with fewer side effects.This current review discussed the potential of scopoletin,a coumarin present in many edible plants,which elicits anticancer properties through multiple mechanisms,including modulating cell cycle arrest,inducing apoptosis,and regulating multiple signaling pathways.Understanding these mechanisms highlights the potential of scopoletin as a candidate for chemoprevention and chemotherapy.