Avoiding misdiagnosis of multilocular thymic cysts as malignant tumors on computer tomography

This editorial provides insights from a case report by Sun et al published in the World Journal of Clinical Cases.The case report focuses on a case where a multilocular thymic cyst(MTC)was misdiagnosed as a thymic tumor,resulting in an unnecessary surgical procedure.Both MTCs and thymic tumors are rare conditions that heavily rely on radiological imaging for accurate diagnosis.However,the similarity in their imaging presentations can lead to misinterpretation,resulting in unnecessary surgical procedures.Due to the ongoing lack of comprehensive knowledge about MTCs and thymic tumors,we offer a summary of diagnostic techniques documented in recent literature and examine potential causes of misdiagnosis.When computer tomography(CT)values surpass 20 Hounsfield units and display comparable morphology,there is a risk of misdiagnosing MTCs as thymic tumors.Employing various differential diagnostic methods like biopsy,molecular biology,multi-slice CT,CT functional imaging,positron emission tomography/CT molecular functional imaging,magnetic resonance imaging and radiomics,proves advantageous in reducing clinical misdiagnosis.A deeper understanding of these conditions requires increased attention and exploration by healthcare providers.Moreover,the continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses,provide appropriate treatment options,and improve the quality of life for patients with thymic tumors and MTCs in the future.continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses,provide appropriate treatment options,and improve the quality of life for patients with thymic tumors and MTCs in the future.

Advances in epidural labor analgesia:Effectiveness and treatment strategies of butorphanol

In this editorial,we provide a critical review of the article by Tang et al published in the World J Clin Cases,focusing on the utilization of butorphanol for epidural analgesia during labor.Our discussion encompasses recent research developments in epidural labor analgesia,specifically highlighting the current status of clinical applications of butorphanol and associated treatment approaches.Epidural analgesia is widely acknowledged as the primary method for pain management during labor,offering effective and prolonged pain relief while allowing mothers to remain alert and actively participate in the delivery process.Among the various drugs utilized for epidural labor analgesia,butorphanol has received increasing attention due to its potential efficacy and distinctive pharmacological properties.As a synthetic opioid analgesic,butorphanol exhibits both agonistic and antagonistic activity on opioid receptors,striking a balance between analgesia and minimizing side effects.Nevertheless,the safety and efficacy of butorphanol in epidural labor analgesia remains controversial.While certain studies have reported positive outcomes with butorphanol,including effective pain relief and a reduced incidence of side effects,others have raised concerns about its safety and efficacy compared to traditional opioids or alternative analgesics.In addition,the optimal dosing strategy and regimen of butorphanol as an adjuvant in epidural labor analgesia still need to be verified.Through comprehensive synthesis and analysis of existing literature,we aim to evaluate the current evidence regarding the use of butorphanol for epidural labor analgesia,delineate areas of consensus and controversy,and propose future avenues for research and clinical practice in this domain.

Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease

Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.

Helicobacter pylori,esophageal precancerous lesions,and proton pump inhibitor overuse

This article reviews the cohort study published in the World Journal of Gastroenterology,which reported low rates of Helicobacter pylori(H.pylori)infection among esophageal cancer(EC)patients,coupled with proton pump inhibitor(PPI)overuse.These findings suggest a potential protective role of H.pylori against EC and indicate a possible association between PPI use and increased cancer risk.In light of these findings,our article examines the complex relationship between H.pylori and esophageal precancerous lesions,exploring the potential underlying mechanisms.We also address growing concerns regarding PPI overuse,including its potential effects on cancer therapy efficacy and the risk of drug interactions.Ultimately,this article highlights the urgent need for further research to evaluate the safety and efficacy of PPIs in cancer patients and to better understand their broader implications.

Intensive care unit-acquired weakness:Unveiling significant risk factors and preemptive strategies through machine learning

This editorial discusses an article recently published in the World Journal of Clinical Cases,focusing on risk factors associated with intensive care unit-acquired weak-ness(ICU-AW).ICU-AW is a serious neuromuscular complication seen in criti-cally ill patients,characterized by muscle dysfunction,weakness,and sensory impairments.Post-discharge,patients may encounter various obstacles impacting their quality of life.The pathogenesis involves intricate changes in muscle and nerve function,potentially leading to significant disabilities.Given its global significance,ICU-AW has become a key research area.The study identified critical risk factors using a multilayer perceptron neural network model,highlighting the impact of intensive care unit stay duration and mechanical ventilation duration on ICU-AW.Recommendations were provided for preventing ICU-AW,empha-sizing comprehensive interventions and risk factor mitigation.This editorial stresses the importance of external validation,cross-validation,and model tran-sparency to enhance model reliability.Moreover,the application of machine learning in clinical medicine has demonstrated clear benefits in improving disease understanding and treatment decisions.While machine learning presents oppor-tunities,challenges such as model reliability and data management necessitate thorough validation and ethical considerations.In conclusion,integrating ma-chine learning into healthcare offers significant potential and challenges.Enhan-cing data management,validating models,and upholding ethical standards are crucial for maximizing the benefits of machine learning in clinical practice.

Strengthening pharmacotherapy research for COVID-19-induced pulmonary fibrosis

The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung injury.This condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few days.While lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant drawbacks.The optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains controversial.Despite this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF.Additionally,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors.Genetic mutations may also impact therapeutic efficacy.Enhancing research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related PF.These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.

Hippocampal neurogenesis and pro-neurogenic therapies for Alzheimer's disease

Adult hippocampal neurogenesis(AHN)facilitates hippocampal circuits plasticity and regulates hippocampus-dependent cognition and emotion.However,AHN malfunction has been widely reported in both human and animal models of Alzheimer's disease(AD),the most common form of dementia in the elderly.Proneurogenic therapies including rescuing innate AHN,cell engraftment and glianeuron reprogramming hold great potential for compensating the neuronal loss and rewiring the degenerated neuronal network in AD,but there are still great challenges to be overcome.This review covers recent advances in unraveling the involvement of AHN in AD and highlights the prospect of emerging proneurogenic remedies.

Copper homeostasis and neurodegenerative diseases

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

Rutaecarpine Inhibits Angiotensin Ⅱ-Induced Proliferation in Rat Vascular Smooth Muscle Cells

Objective： To evaluate the effects and possible mechanisms of rutaecarpine on angiotensin Ⅱ （Ang Ⅱ ）-induced proliferation in cultured rat vascular smooth muscle cells （VSMCs）. Methods： VSMCs were isolated from Male Sprague-Dawley rat aorta, and cultured by enzymic dispersion method. Experiments were performed with cells from passages 3-8. The cultured VSMCs were randomly divided into control, model （Ang Ⅱ 0.1 μ moVL）, and rutaecarpine （0.3-3.0μmol/L） groups. VMSC proliferation was induced by Ang Ⅱ, and was evaluated by the 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide assay and cell counting. To examine the mechanisms involved in anti-proliferative effects of rutaecarpine, nitric oxide （NO） levels and NO synthetase （NOS） activity were determined. Expressions of VSMC proliferation-related genes including endothelial nitric oxide synthase （eNOS）, and c-myc hypertension related gene-1 （HRG-1） were determined by real-time reverse chain reaction （RT-PCR）. Results： Rutaecarpine （0.3-3.0μmol/l_） inhibited Ang R-induced VSMC proliferation and the best effects were achieved at 3.0 μmol/L. The Ang Ⅱ-induced decreases in cellular NO contents and NOS activities were antagonized by rutaecarpine （P〈0.05）. Ang Ⅱ administration suppressed the expressions of eNOS and HRG-1, while increased c-myc expression （P〈0.05）. All these effects were attenuated by 3.0μmol/L rutaecarpine （P〈0.05）. Conclusion： Rutaecarpine is effective against Ang Ⅱ-induced rat VSMC proliferation, and this effect is due, at least in part, to NO production and the modulation of VMSC proliferation-related gene expressions.

Rutaecarpine Inhibits Intimal Hyperplasia in A Balloon-Injured Rat Artery Model

Objective： To investigate the effect and potential mechanisms of rutaecarpine （Rut） in a rat artery balloon-injury model. Methods： The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery （CCA） of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut （25, 50 and 75 mg/kg） with 10 rats of each group. The rats were treated with or without Rut （25, 50, 75 mg/kg） by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen （PCNA） and smooth muscle （SM） oL-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 （ERK2）, MAPK phosphatase-1 （MKP-1） and endothelial nitric oxide synthase （eNOS） were determined by real-time reverse chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 （p-ERK2） were examined by Western blotting. The plasma contents of nitric oxide （NO） and cyclic guanosine 3＇,5＇-monophosphate （cGMP） were also determined. Results： Compared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury （P〈0.05 or P〈0.01）. The positive expression rate of PCNA was decreased, while the expression rate of SM α -actin obviously increased in the vascular wall after Rut （50 and 75 mg/kg） administration （P〈0.05 or P〈0.01）. Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated （P〈0.05 or P〈0.01）. The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downragulated after Rut （50 and 75 mg/kg） administration （P〈0.05 or P〈0.01）, respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma （P〈0.05 or P〈0.01）. Conclusion： Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.

The crosstalk between the caspase family and the cGAS-STING signaling pathway

Cytosolic nucleic acid sensors are critical for sensing nucleic acids and initiating innate immunity during microbial infections and/or cell death.Over the last decade,several key studies have characterized the conserved mechanism of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and the downstream signaling adaptor stimulator of interferon genes(STING)initiating the innate immune signaling pathways.Aside from its primary involvement in microbial infections and inflammatory diseases,there is growing interest in the alternate roles of cGAS-STING-mediated signaling.Caspase family members are powerful functional proteins that respond to cellular stress,including cell death signals,inflammation,and innate immunity.Recent studies have uncovered how the caspase family cooperates with the cGAS-STING signaling pathway.Most caspase family members negatively regulate the cGAS-STING signaling pathway.In turn,some caspase family members can also be modulated by cGAS-STING.This review gives a detailed account of the interplay between the caspase family and the cGAS-STING signaling pathway,which will shed light on developing novel therapeutics targeting the caspase family and cGAS-STING signaling in antiviral innate immunity,cancer,inflammatory,and autoimmunity.

Evodiamine Inhibits Angiotensin Ⅱ-Induced Rat Cardiomyocyte Hypertrophy

Objective: To investigate the effects of evodiamine(Evo), a component of Evodiaminedia rutaecarpa(Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and further explore the potential mechanisms. Methods: Cardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model(Ang Ⅱ 0.1 μmol/L), and Evo(0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium([Ca]i) concentration, activity of nitric oxide synthase(NOS) and content of nitric oxide(NO) were measured, respectively. The m RNA expressions of atrial natriuretic factor(ANF), calcineurin(CaN), extracellular signal-regulated kinase-2(ERK-2), and endothelial nitric oxide synthase(e NOS) of cardiomyocytes were analyzed by real-time reverse transcriptionpolymerase chain reaction. The protein expressions of calcineurin catalytic subunit(CnA) and mitogen-activated protein kinase phosphatase-1(MKP-1) were detected by Western blot analysis. Results: Compared with the control group, Ang Ⅱ induced cardiomyocytes hypertrophy, as evidenced by increased cardiomyocyte surface area, protein content, and ANF m RNA expression; increased intracellular free calcium([Ca]i) concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but decreased MKP-1 protein expression(P<0.05 or P<0.01). Compared with Ang Ⅱ, Evo(0.3, 3 μmol/L) significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, decreased the [Ca]i concentration and expressions of CaN m RNA, CnA protein, and ERK-2 m RNA, but increased MKP-1 protein expression(P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the e NOS m RNA expression(P<0.05). Conclusion: Evo significantly attenuated Ang Ⅱ-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca]i concentration, and inhibition of CaN and ERK-2 signal transduction pathways.

A novel dephosphorylation targeting chimera selectively promoting tau removal in tauopathies

Intraneuronal accumulation of hyperphosphorylated tau is a hallmark pathology shown in over twenty neurodegenerative disorders,collectively termed as tauopathies,including the most common Alzheimer's disease(AD).Therefore,selectively removing or reducing hyperphosphorylated tau is promising for therapies of AD and other tauopathies.Here,we designed and synthesized a novel DEPhosphorylation TArgeting Chimera(DEPTAC)to specifically facilitate the binding of tau to Ba-subunit-contalning protein phosphatase 2A(PP2A-Ba),the most active tau phosphatase in the brain.The DEPTAC exhibited high efficiency in dephosphorylating tau at multiple AD-associated sites and preventing tau accumulation both in vitro and in vivo.Further studies revealed that DEPTAC significantly improved microtubule assembly,neurite plasticity,and hippocampus-dependent learning and memory in transgenic mice with inducible overexpression of truncated and neurotoxic human tau N368.Our data provide a strategy for selective removal of the hyperphosphorylated tau,which sheds new light for the targeted therapy of AD and related-tauopathies.

Compensation for Neurodegeneration by Hippocampal Neurogenesis in Alzheimer’s Disease: Where is the way?

Neurodegeneration,a defining hallmark of Alzheimer's disease(AD),features the progressive loss of neuronal structure and functions.Therapeutic approaches to AD show limited efficiency in halting the neurodegeneration to date.Given the lack of neuronal renewability in most subareas of the adult brain,symptomatic drugs or treatments cannot repopulate neurons and rewire the degenerated neuronal circuits in AD.