Engineered AAV13 variants with enhanced transduction and confined spread

Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the context of brain diseases.Adeno-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain regions.However,AAV13 mediates relatively low expression of target genes.Here,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency.We first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid.We then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,respectively.We found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread range.These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

The association between C-reactive protein to albumin ratio and 6-month neurological outcome in patients with in-hospital cardiac arrest

The global incidence rates of in-hospital cardiac arrest(IHCA)range from1.2 to 9.0 per1,000 hospitalized patients,as per the National Cardiac Arrest Database.[1] While IHCAs tend to exhibit superior 30-day survival rates relative to out-of-hospital cardiac arrests (OHCA) due to situational advantages,such as immediate access to medical personnel and treatments.

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of life.These complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality rates.Despite the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac surgery.Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength.Early mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance exercises.Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity.During the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac rehabilitation.By incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

The Antidepressant Mechanism of JiaWeiWenDan Decoction Regulating p38MAPK-ERK5 Signal Transduction Pathway

Objective: To investigate the anti-depression mechanism of JiaWeiWenDan Decoction in regulating p38MAPK-ERK5 signal transduction pathway. Methods: Depression model rats were randomly divided into Blank Control Group, Model Control Group, Chinese Medicine Treatment Group, and Western Medicine Treatment Group (hereinafter referred to as Blank Group, Model Group, Chinese Medicine Group, and Western Medicine Group), with 48 rats in each group. The mice were treated with p38MAPK-ERK5 on the 7th day, 14th day and 21st day, respectively, and the mice were treated for 28 days. The key targets and cytokines in p38MAPK-ERK5 signal transduction pathway were detected. Results: Compared with the Blank Group, the expression of p38MAPKmRNA in the hippocampus of the Model Group was increased. The Chinese Medicine Group and Western Medicine Group could reduce the expression of p38MAPK mRNA (P P P P Conclusion: The anti-inflammatory effect of JiaWeiWenDan Decoction may be related to the regulation of p38MAPK-ERK5 signaling pathway. With the advance of the treatment week, the best effect was obtained when the treatment was started on the 7th day of modeling.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery:A systematic review

BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.

Bibliometric analysis of the global research status and trends of mechanotransduction in cancer

BACKGROUND The development of cancer is thought to involve the dynamic crosstalk between the tumor cells and the microenvironment they inhabit.Such crosstalk is thought to involve mechanotransduction,a process whereby the cells sense mechanical cues such as stiffness,and translate these into biochemical signals,which have an impact on the subsequent cellular activities.Bibliometric analysis is a statistical method that involves investigating different aspects(including authors’names and affiliations,article keywords,journals and citations)of large volumes of literature.Despite an increase in mechanotransduction-related research in recent years,there are currently no bibliometric studies that describe the global status and trends of mechanotransduction-related research in the cancer field.AIM To investigate the global research status and trends of mechanotransduction in cancer from a bibliometric viewpoint.METHODS Literature on mechanotransduction in cancer published from January 1,1900 to December 31,2022 was retrieved from the Web of Science Core Collection.Excel and GraphPad software carried out the statistical analysis of the relevant author,journal,organization,and country information.The co-authorship,keyword cooccurrence,and keyword burst analysis were visualized with VOSviewer and CiteSpace.RESULTS Of 597 publications from 745 institutions in 45 countries were published in 268 journals with 35510 citation times.With 270 articles,the United States is a well-established global leader in this field,and the University of California system,the most productive(n=36)and influential institution(n=4705 citations),is the most highly active in collaborating with other organizations.Cancers was the most frequent publisher with the highest H-index.The most productive researcher was Valerie M.Weaver,with 10 publications.The combined analysis of concurrent and burst keywords revealed that the future research hotspots of mechanotransduction in cancer were related to the plasma membrane,autophagy,piezo1/2,heterogeneity,cancer diagnosis,and post-transcriptional modifications.CONCLUSION Mechanotransduction-related cancer research remains a hot topic.The United States is in the leading position of global research on mechano-oncology after almost 30 years of investigations.Research group cooperations exist but remain largely domestic,lacking cross-national communications.The next big topic in this field is to explore how the plasma membrane and its localized mechanosensor can transduce mechanical force through post-transcriptional modifications and thereby participate in cellular activity regulations and cancer development.

Left bundle branch pacing set to outshine biventricular pacing for cardiac resynchronization therapy?

The deleterious effects of long-term right ventricular pacing necessitated the search for alternative pacing sites which could prevent or alleviate pacinginduced cardiomyopathy.Until recently,biventricular pacing(BiVP)was the only modality which could mitigate or prevent pacing induced dysfunction.Further,BiVP could resynchronize the baseline electromechanical dssynchrony in heart failure and improve outcomes.However,the high non-response rate of around 20%-30%remains a major limitation.This non-response has been largely attributable to the direct non-physiological stimulation of the left ventricular myocardium bypassing the conduction system.To overcome this limitation,the concept of conduction system pacing(CSP)came up.Despite initial success of the first CSP via His bundle pacing(HBP),certain drawbacks including lead instability and dislodgements,steep learning curve and rapid battery depletion on many occasions prevented its widespread use for cardiac resynchronization therapy(CRT).Subsequently,CSP via left bundle branch-area pacing(LBBP)was developed in 2018,which over the last few years has shown efficacy comparable to BiVP-CRT in small observational studies.Further,its safety has also been well established and is largely free of the pitfalls of the HBP-CRT.In the recent metanalysis by Yasmin et al,comprising of 6 studies with 389 participants,LBBPCRT was superior to BiVP-CRT in terms of QRS duration,left ventricular ejection fraction,cardiac chamber dimensions,lead thresholds,and functional status amongst heart failure patients with left bundle branch block.However,there are important limitations of the study including the small overall numbers,inclusion of only a single small randomized controlled trial(RCT)and a small follow-up duration.Further,the entire study population analyzed was from China which makes generalizability a concern.Despite the concerns,the meta-analysis adds to the growing body of evidence demonstrating the efficacy of LBBP-CRT.At this stage,one must acknowledge that the fact that still our opinions on this technique are largely based on observational data and there is a dire need for larger RCTs to ascertain the position of LBBPCRT in management of heart failure patients with left bundle branch block.

Approach to cardiac masses: Thinking inside and outside the box

In this editorial we comment on the article by Huffaker et al,published in the current issue of the World Journal of Clinical Cases.Cardiac masses encompass a broad range of lesions,potentially involving any cardiac structure,and they can be either neoplastic or non-neoplastic.Primitive cardiac tumors are rare,while metastases and pseudotumors are relatively common.Cardiac masses frequently pose significant diagnostic and therapeutic challenges.Multimodality imaging is fundamental for differential diagnosis,treatment,and surgical planning.In particular cardiac magnetic resonance(CMR)is currently the gold standard for noninvasive tissue characterization.CMR allows evaluation of the relationship between the tumor and adjacent structures,detection of the degree of infiltration or expansion of the mass,and prediction of the possible malignancy of a mass with a high accuracy.Different flow charts of diagnostic work-up have been proposed,based on clinical,laboratory and imaging findings,with the aim of helping physicians approach the problem in a pragmatic way(“thinking inside the box”).However,the clinical complexity of cancer patients,in particular those with rare syndromes,requires a multidisciplinary approach and an open mind to go beyond flow charts and diagnostic algorithms,in other words the ability to“think outside the box”.

A contradictory phenomenon of thicken pericardium and cardiac compression without inferior vena cava dilation:sign of IVC escape

A 77-year-old female presented with shortness of breath and tightness of chest was admitted.Her past medical history included hypertension and she has been taking nifedipine regularly.Two years before,she was diagnosed with pericardial effusion(Figure 1)and had pericardiocentesis drainage.On physical examination,her blood pressure was 151/100 mm-Hg and her pulse rate was 91 beats/min.

Total suprarenal aortic occlusion with cardiac disease: a case series of three cases

Acute aortic occlusion(AAO)has been very rarely reported in the literature and is a potentially life-threatening emergency.[1-5]AAO mostly occurs in cardiac disease patients,[1-4,6,7]and leads to cardiac complications.[1,2,5,6]Suprarenal aortic occlusion(SAO)is a very rare type of AAO,and infrarenal aortic occlusion(IAO)accounts for 75.8%-97.8%.[1,3,5-7]SAO is different from IAO in some clinical manifestations,treatment strategies,and prognoses.[3,6-8]SAO with cardiac disease will make the condition more complex and could easily cause a delay in diagnosis and portend worse outcomes with amputation and mortality rates.[1,3,6]Early and fast diagnosis and positive revascularization treatment are necessary to prevent cases from becoming fatal.[1-3]Herein,we present a case series of SAO with cardiac disease.

Diagnostic Dilemma of Intracardiac Mass: Tumor versus Thrombus-Case Series and Systematic Review

Background: The differential diagnosis for intracavitary cardiac masses is limited, typically including vegetations, tumors, or thrombi. Cardiac thrombi can often mimic cardiac tumors on imaging, creating a diagnostic challenge. Primary cardiac tumors are rare and usually benign, whereas most cardiac tumors result from metastases, commonly originating from malignancies in the breast, lung, or melanoma. Aim: This report highlights the importance of distinguishing various cardiac masses based on clinical presentations, clinical courses, and radiological features. Case Presentation: We describe two cases of cardiac masses with unique and diverse clinical features. Each case posed significant diagnostic challenges due to their distinct presentations and clinical progressions. Conclusion: These cases underscore the importance of considering both benign and metastatic origins in the differential diagnosis of intracavitary cardiac masses. Accurate differentiation between thrombi and tumors is crucial for appropriate management and treatment.

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.

Utilization of biomarkers for the prognostic prediction of cardiac arrest survivors using a multi-modal approach

International guidelines for post-cardiac arrest care recommend using multi-modal strategies to avoid the withdrawal of life-sustaining therapy(WLST)in patients with the potential for neurological recovery.[1]However,a clear methodology for multi-modal approaches has yet to be developed.Neuron-specific enolase(NSE)is currently the only recommended biomarker,and the European Resuscitation Council(ERC)and the European SocietyofIntensiveCareMedicine(ESICM)have proposed a cutoff value of 60μg/L at 48 and/or 72 h after the return of spontaneous circulation(ROSC)as a multimodal prognostic tool for predicting poor neurological outcomes.

Disorders of cardiac rhythm in China

The Annual Report on Cardiovascular Health and Diseases in China(2022)intricate landscape of cardiovascular health in China.In connection with the previous section,this seventh section of the report offers a comprehensive analysis of dis-orders of heart rhythm in China.In 2021,China has achieved significant development and gratifying results in many aspects of the field of arrhythmia.Left bundle branch pacing(LBBP),as an emerging pacing technique originating from China,has received widespread attention.New research results have emerged on its indications,surgical procedures,clinical evaluation,and com-parison with other pacing techniques.Its feasibility,effectiveness,and safety have been basically verified,but its long-term pro-gnosis still needs further confirmation from larger samples and longer follow-up time research results.Leadless pacemakers have begun to be used in a wider range of clinical applications,and related large sample cohort studies have been reported.In addi-tion,there are also noteworthy new achievements in the fields of pacemaker remote programming,anticoagulation and radiofre-quency catheter ablation(RFCA)therapy for atrial fibrillation,and implantable cardioverter defibrillator prevention of sudden cardiac death.In terms of clinical practice,due to COVID-19 pandemic,the number of RFCA procedures and other device im-plantations in China has fluctuated,but it has gradually recovered since 2020.

Multimodal cardiac imaging assisted tumor characterization and surgical planning of a patient with rare primary cardiac paraganglioma

Paragangliomas,also known as pheochromocytomas(1–9 cases per million),arise in the paraganglia.[1]Pheochromocytomas occur in the adrenal glands,while paragangliomas occur elsewhere.[2]Paragangliomas originate from paraganglion cells,which are derived from the neural ectoderm of the nerves and migrate along both sides of the median axis from the base of the skull to the pelvis during embryonic development.

Cardiac infiltration of diffuse large B-cell lymphoma manifesting as sustained ventricular tachycardia:a case report

Cardiac tumors are rare.However,cardiac metastases can occur in up to 10%of patients with cancer.Among cardiac neoplasms,metastases are much more common than primary cardiac tumors.[1]Metastatic cardiac neoplasms most frequently metastasize from the respiratory system.

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Effect of cardiac rehabilitation care after coronary intervention on cardiac function recovery and negative mood in patients with myocardial infarction

BACKGROUND Cardiovascular disease,particularly myocardial infarction(MI)profound impact on patients'quality of life and places a substantial burden on the healthcare and economy systems.Developments in medical technology have led to the emer-gence of coronary intervention as an essential method for treating MI.AIM To assess the effects of cardiac rehabilitation care on cardiac function recovery and negative emotions in MI after coronary intervention.METHODS This study included a total of 180 patients with MI during the period from June 2022 to July 2023.Selected patients were divided into two groups:An observation group,which receiving cardiac rehabilitation care;a control group,which re-ceiving conventional care.By comparing multiple observation indicators such as cardiac function indicators,blood pressure,exercise tolerance,occurrence of adverse cardiac events,and negative emotion scores between the two groups of patients.All the data were analyzed and compared between two groups.RESULTS There were 44 males and 46 females in the observation group with an average age of 36.26±9.88 yr;there were 43 males and 47 females in the control group,with an average age of 40.87±10.5 yr.After receiving the appropriate postoperative nursing measures,the results of the observation group showed significant improvement in several indicators compared with the control group.Indicators of cardiac function,such as left ventricular end-diastolic internal diameter and left ventricular ejection fraction were significantly better in the observation group than in the control group(P<0.05).Exercise endurance assessment showed that the 6-minute walking test distance was significantly increased in the patients of the observation group(P<0.01).In addition,the incidence of adverse cardiac events was significantly lower in the observation group,and negative mood scores were significantly reduced(P<0.05).CONCLUSION Cardiac rehabilitation care after coronary intervention has a significant positive impact on functional recovery.This emphasizes the importance of cardiac rehabilitation care to improve patient recovery.

Interest of Cardiac Rehabilitation in Patients with Heart Disease in a Cardiology Department in Senegal

Cardiac rehabilitation helps improve the prognosis and quality of life for patients with heart disease. To show its interest in the African context, in the management of heart disease, a prospective study was carried out. Its objective was to evaluate the effects of physical rehabilitation on cardiac function. Methods: Patients were evaluated at the beginning and at the end of cardiovascular rehabilitation by cardiovascular, biological, and echocardiographic parameters including the size of the heart chambers, the kinetics of the walls, and the systolic function of the ventricles. Results: The study involved 12 patients, 67% of whom were men. After cardiac rehabilitation, the mean hemodynamic constants had not been significantly modified. However, a significant decrease in Total-Cholesterol, LDL-Cholesterol and triglyceride levels was noted. Mean fasting blood sugar decreased from 1.25 ± 0.48 g/L to 0.92 ± 0.18 g/L and glycated hemoglobin from 7.72% ± 0.01% to 6.45% ± 0.008%. The echocardiographic parameters studied showed an improvement in the dilation of the heart chambers in 8.33% of the patients, the normalization of the ejection fraction of the left ventricle in 16% patients, the improvement of the kinetic disorders in 16% of patients and recovery of right ventricular systolic function in all patients. Conclusion: Cardiac rehabilitation as a secondary preventive measure for cardiovascular disease has contributed significantly to improving the clinico-biological parameters of the disease.

Cardiac Tolerance of Hydroalcoholic Extract of Bark of Terminalia mantaly H. Perrier (HAEBTM) in Wistar Rats

Terminalia mantaly H. Perrier is a plant used in traditional medicine for the treatment of various pathologies. However, Terminalia mantaly H. Perrier could present potential health effects on patients. In order to determine the possible cardiotoxic effects of the hydro-alcoholic extract of the bark of Terminalia mantaly H. Perrier, (HAEBTM) forty (40) rats distributed randomly into 4 groups, including 10 animals per group (5 males and 5 females) were used. Animals in group 1 received distilled water and were used as a control group. On the other hand, groups 2, 3, 4 received oral administration a volume of the hydroalcoholic extract of Terminalia mantaly H. Perrier corresponding to 1 mL/100g of body weight at 150 mg/kg, 300 mg/kg, 600 mg/kg, respectively. The extract was administered daily at the same time for 28 days and serum was collected once a week to evaluate cardiac biochemical markers using spectrophotometric methods using a Cobas C311 HITACHI biochemistry system. After one month of study, all rats were euthanized by overdose of ether, and the hearts of the rats were removed for gross morphological and histopathological analysis. Results were analysed using variance analysis (ANOVA) to compare outcomes as a function of doses administered and treatment times. The biochemical parameters ALT, LDH, CPK, CPKMB showed no significant change (p Terminalia mantaly showed no lesions, edema and necrosis. These results suggest that the hydroalcoholic extract of Terminalia mantaly did not interfere with the functioning or alter the integrity of the heart.