Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: ...Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.展开更多
Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and com...Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.展开更多
Selective internal radiation therapy using yttrium-90 has been used to treat hepatocellular carcinoma,intrahepatic cholangiocarcinoma,and other malignant tumors that have spread to the liver locally.The authors used t...Selective internal radiation therapy using yttrium-90 has been used to treat hepatocellular carcinoma,intrahepatic cholangiocarcinoma,and other malignant tumors that have spread to the liver locally.The authors used the bibliometric approach in response to the neoplasms,using the keyword“Yttrium 90 AND Liver Neoplasms”as a search parameter and then looked up pertinent English-language literature in the Web of Science core collection database’s selfbuilt database through November 30,2025.For statistical analysis and literature management,EndNote and Excel tools were utilized.In addition to co-citation and emergent keyword analysis of authors,VOSviewer and CiteSpace were utilized for social network and chronological order of countries,institutions,authors,and keywords.The aim of this study was to serve as a reference for future research by methodically sorting through the international research literature on Yttrium 90 treatment of liver neoplasms and summarizing the research status and hot trends in this field.In recent years,research focus has increasingly shifted toward high-quality,multi-center clinical trials that combine SIRT-targeted systemic therapy with hepatectomy following the descending stage.This approach is likely to remain a significant research trend in the field.展开更多
The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from...The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.展开更多
Time-delayed blasting is widely utilized in engineering to mitigate induced vibration hazards and enhance fragmentation.The underlying vibration reduction principle is the decrease of the charge weight per delay,while...Time-delayed blasting is widely utilized in engineering to mitigate induced vibration hazards and enhance fragmentation.The underlying vibration reduction principle is the decrease of the charge weight per delay,while the potential for further vibration reduction remains debated,largely due to unclear underlying mechanisms.In light of the popularization of electronic detonators and the representativeness of double-hole configurationsfor multiple blastholes,it is essential to investigate the vibration characteristics induced by time-delayed double blastholes.Therefore,a series of doubleborehole experimental blasts was conducted in an underground roadway to clarify the variation in vibration from single-hole to dual-hole conditions.Based on the experimental data and inherent limitations,an exact full-fieldtheoretical model was further employed to systematically analyze the effects of delay time,charge length,and borehole inclination angle on vibrations induced by various doublehole configurations.The experimental data and theoretical analysis reveal that the general scaled distance effectively predicts vibrations in delayed blasting but does not reflectvibration reduction.Increasing delay time causes fluctuatingPPVs,which stabilize slightly above single-hole PPVs as delay times exceed a certain value.The delayed blasting primarily reduces near-fieldfrequencies.Longer charge lengths in double boreholes increase PPV levels and attenuation rates within a certain length,and the vibration behavior of combined long and short charge lengths is governed by the long blasthole.Larger blasthole inclination angles enhance vibration amplitude and reduce PPV attenuation rates.Optimizing inclination angles is more critical than adjusting delay times,and parallel boreholes offer the best vibration control.展开更多
Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecul...Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.展开更多
Recovered samples of Jilin H5 chondrite experimentally shocked to 12-133 GPa were studied to explore the behavior of opaque minerals under shock loading using SEM-EDS,Raman spectroscopy,and TIMA.The following results ...Recovered samples of Jilin H5 chondrite experimentally shocked to 12-133 GPa were studied to explore the behavior of opaque minerals under shock loading using SEM-EDS,Raman spectroscopy,and TIMA.The following results were obtained.Firstly,at pressures lower than 53GPa,the opaque minerals still keep the unmelted state,while at 78 GPa and higher,FeNi metal and troilite form eutectic intergrowths occurring as disorderly fine veinlets filling the shock-induced fractures in silicate minerals.Secondly,single kamacite grains still maintain their contour at 12 GPa,but a part of brittle troilite grains was fragmented and squeezed into the shock-induced fractures within kamacite grains.At53 and 133 GPa,many more troilite fragments are poured in the kamacite interior to form disordered hybrid aggregates or to form squiggly strips,respectively.Similar phenomena are observed within single troilite grains,but the mineral squeezed into troilite grains is kamacite.Thirdly,chromite is a hard and refractory oxide mineral.When the shock pressure rises step by step from 12 to 133 GPa,the shock effect of chromite is only fragmentation.Its grain size decreases from tens of um at 53 GPa to a few um at 133 GPa.And,fourthly,native copper exhibits distinct redistribution behavior at high temperature.In Jilin samples shock-loaded to 12 GPa,copper initially located at troilite-kamacite interfaces partially transferred into small troilite grains containing fine FeNi particles.At 53 and 133 GPa,native copper preferentially transferred into larger troilite grains containing more particles of eutectic FeNi metal.展开更多
To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was struct...To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.展开更多
The shear adhesive strength at the clay‒metal interfaces serves as a critical parameter for evaluating the soil adhesion and metal interface mudding phenomena.However,its rapid determination remains challenging becaus...The shear adhesive strength at the clay‒metal interfaces serves as a critical parameter for evaluating the soil adhesion and metal interface mudding phenomena.However,its rapid determination remains challenging because of the demanding requirements for high-precision instrumentation and complex calibration procedures.In this study,an integrated framework was presented that combined physical experiments,theoretical approaches,and machine learning to enable the autonomous determination of the shear adhesive strength of soil under multiple influencing factors.We developed an improved particle swarm optimization-optimized ordinary kriging(IPOK)surrogate testing method to enhance the limited experimental datasets,and a lightweight residual neural network(RLNet)was then used for effective intra-and extra-domain predictions.A comprehensive model discussion,comparison,and interpretability analysis were conducted.The results from 64 physical experiments considering the consistency index,normal stress,clay content,rotation rate,and disc material effectively characterized the shear adhesion behaviour of kaolin.The IPOK surrogate experiments successfully replicated the physical data points while enriching the dataset details.The RLNet model trained with IPOK data achieved superior prediction performance,with a root mean square error of 7.491 and a determination coefficient of 0.927 in 16 orthogonal validation tests,and high similarity was attained between the predicted and measured values.A detailed model discussion analysis confirmed the superiority of the IPOK-RLNet framework.This methodology provides a cost-effective rapid analysis technique for assessing clay‒metal interface shear adhesion,significantly reducing laboratory testing requirements and experimental costs while increasing engineering efficiency.展开更多
Appendiceal mucinous neoplasms(AMNs)are rare tumors originating from mucin-producing epithelial cells of the appendix.They can exhibit both benign and malignant behavior.They are often incidentally discovered during a...Appendiceal mucinous neoplasms(AMNs)are rare tumors originating from mucin-producing epithelial cells of the appendix.They can exhibit both benign and malignant behavior.They are often incidentally discovered during appendectomy.Clinical presentation ranges from asymptomatic to mimicking acute appendicitis.Histologically,noninvasive AMNs are classified as low-grade AMNs(LAMNs)or high-grade AMNs(HAMNs),whereas invasive tumors are categorized as mucinous adenocarcinomas.Although LAMNs and HAMNs are generally nonmalignant,rupture can lead to pseudomyxoma peritonei(PMP).Surgical resection is the primary diagnostic and therapeutic approach,with intraoperative assessment to prevent rupture.Treatment strategies vary based on findings and include appendectomy,right hemicolectomy,and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Histological diagnosis relies on mucin detection,and immunohistochemical markers such as cytokeratin 20(diffusely positive),cytokeratin 7(often negative),mucin 5AC,and special ATrich sequence-binding protein 2 assist in characterization.Molecular profiling frequently identifies KRAS,GNAS,and TP53 mutations.KRAS mutations are generally associated with a favorable prognosis,whereas GNAS and TP53 mutations correlate with poorer survival outcomes.These findings highlight the potential role of molecular profiling in guiding treatment strategies for AMN and PMP.展开更多
Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NEN...Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NENs.Historically,GEP-NENs have been regarded as infrequent and slow-growing malignancies;however,recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades.In addition,an increasing number of studies have proven that GEP-NENs result in a limited life expectancy.These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed.Therefore,there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs.In this review,we have summarized the limitations and recent advancements in our comprehension of the epidemiology,clinical presentations,pathology,molecular biology,diagnosis,and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.展开更多
To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cr...To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].展开更多
BACKGROUND Pancreatic cystic neoplasms(PCNs)are increasingly detected due to advancements in radiographic techniques,with a prevalence of approximately 15%in the general population.These lesions range from benign to p...BACKGROUND Pancreatic cystic neoplasms(PCNs)are increasingly detected due to advancements in radiographic techniques,with a prevalence of approximately 15%in the general population.These lesions range from benign to premalignant and malignant,posing a diagnostic challenge.Accurate differentiation is critical,as premalignant and malignant PCNs often require surgical intervention,while benign cysts may only need monitoring unless symptomatic.Current diagnostic methods,including cross-sectional imaging,endoscopic ultrasonography,and endoscopic ultrasonography-guided fine-needle aspiration/biopsy,are specialized,not universally available,and have variable accuracy.Clinical and laboratory parameters such as carbohydrate antigen 19-9(CA 19-9),neutrophillymphocyte ratio,platelet-lymphocyte ratio,and red cell distribution width(RDW)have been associated with malignancy risk,though only CA 19-9 is guideline-supported.AIM To assess the malignancy risk of PCNs using preoperative clinical and routine laboratory parameters.METHODS A retrospective cohort study analyzed 70 patients who underwent surgery for PCNs at Ankara Bilkent City Hospital between February 2019 and March 2023.Patients were categorized into group A(benign or low-grade dysplasia,n=40)and group B(malignancy or high-grade dysplasia,n=30)based on postoperative pathology.Preoperative demographic and laboratory parameters,including age,RDW,albumin,and CA 19-9,were compared.Univariate and multivariate logistic regression analyses identified independent predictors of malignancy.Receiver operating characteristic curve analysis evaluated predictive performance,with internal validation using bootstrapping.RESULTS Group B patients were older(69.86±9.58 years vs 52.74±16.85 years,P<0.001)and had a higher incidence of diabetes mellitus(57.1%vs 21.4%,P=0.002).RDW(16.2%vs 13.7%,P<0.001),platelet-lymphocyte ratio(178 vs 126,P=0.008),and CA 19-9(21.7 U/mL vs 9.3 U/mL,P=0.009)were significantly higher in group B,while albumin was lower(41 g/L vs 45 g/L,P=0.008).Multivariate analysis identified age[odds ratio=1.067,95%confidence interval(CI):1.014-1.122,P=0.012]and RDW(odds ratio=1.784,95%CI:1.172-2.715,P=0.007)as independent predictors.The area under the curve for age,RDW,and their combination was 0.798(95%CI:0.695-0.900),0.801(95%CI:0.692-0.911),and 0.858(95%CI:0.771-0.944),respectively,with bootstrapped validation confirming stability.Cut-off values of age≥60 years and RDW≥15.5%balanced sensitivity and specificity,increasing malignancy risk 15.3-fold and 22.6-fold,respectively.CONCLUSION Age and RDW are independent predictors of malignancy in PCNs,aiding in patient selection for advanced diagnostics and surgery.Larger,multicenter studies are needed to validate these findings.展开更多
Pancreatic cystic neoplasms(PCNs) are a diverse group of neoplasms in the pancreas,and are more increasingly encountered with widespread abdominal screening and improved imaging techniques.The most common types of PCN...Pancreatic cystic neoplasms(PCNs) are a diverse group of neoplasms in the pancreas,and are more increasingly encountered with widespread abdominal screening and improved imaging techniques.The most common types of PCNs are serous cystic neoplasms(SCNs),mucinous cystic neoplasms(MCNs),and intraductal papillary mucinous neoplasms(IPMNs).Clinicians frequently feel bewildered in the differential diagnosis and subsequent management among the various types of lesions in the pancreas,which may lead to overtreatment or delayed treatment.The current review provides recent developments in the understanding of the three most common types of PCNs,the latest modalities used in preoperative diagnosis and differential diagnosis,as well as the most up to date management.Suggestions for diagnosis and differential diagnosis of SCNs,MCNs,and IPMNs are also provided for young surgeons.Better understanding of these neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients.展开更多
Neuroendocrine neoplasms(NENs)are relatively rare tumors that arise from peptidergic neurons and neuroendocrine cells.NENs are highly heterogeneous and can occur in any part of the body,with a particular prevalence in...Neuroendocrine neoplasms(NENs)are relatively rare tumors that arise from peptidergic neurons and neuroendocrine cells.NENs are highly heterogeneous and can occur in any part of the body,with a particular prevalence in the digestive system.NENs consist of a range of tumor types and the biological behaviors exhibit significant differences.NENs are classified into well-differentiated neuroendocrine tumors(NETs)and poorly differentiated neuroendocrine carcinomas(NECs).NETs can be further classified and graded into the following three categories:low-grade NETs,grade 1(NET G1);intermediate-grade NET G2;and high-grade NET G3.NECs include large cell-type NEC(LCNEC)and small cell-type NEC(SCNEC),both of which are considered high grade.Currently,the main treatments for advanced NENs are biological treatments,targeted therapy,chemotherapy,and newer treatments that are still under development,such as immunotherapy and peptide receptor radionuclide therapy(PRRT).However,owing to the rarity of NENs,pharmaceutical company investment is limited and few phase Ⅲ studies have targeted advanced NENs.Most current research consists of investigator-initiated phase Ⅰ and Ⅱ clinical trials or largescale retrospective studies.NEN treatment should be chosen carefully because it is cumbersome and complicated,as indicated above.Herein,we comprehensively summarize the clinical application status and research progress for advanced NEN treatment regimens,especially for advanced NETs,which may help to create awareness on NENs among medical professionals across specialties.展开更多
Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extra...Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particu...BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particularly in the vertical direction.Endoscopic full-thickness resection(EFTR)has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs,including 132 who underwent endoscopic submucosal dissection(ESD)and 28 who underwent EFTR.Lesions were categorized as<1 cm,1-2 cm,and>2 cm in size.CR rate,en bloc resection rate,operation time,and complications were evaluated.Subgroup analyses and follow-up were also performed.RESULTS EFTR achieved 100%CR rates for lesions<1 cm and 1-2 cm,compared with 67.0%and 50.0%,respectively,in the ESD group.En bloc resection and successful removal of the R-NENs were achieved in all patients.Meanwhile,EFTR showed performance comparable to ESD in terms of operation time,hospitalization cost,and postoperative adverse events,except for a one-day longer hospital stay.We also analyzed the invasion depth of R-NENs based on full-thickness specimens.The data showed that 80%of lesions(<1 cm)and 85.7%of lesions(1-2 cm)had invaded the SM3 level or deeper at the time of resection.For ESD specimens,46.6%(<1 cm)and 89.3%(1-2 cm)of lesions had infiltrated more than 2000μm beneath the muscularis mucosae.CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.展开更多
OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and ...OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.展开更多
BACKGROUND Underwater endoscopic mucosal resection(UEMR)has been shown to be a good treatment option for the management of nonpedunculated polyps≥10 mm since its introduction.However,there is a paucity of randomized ...BACKGROUND Underwater endoscopic mucosal resection(UEMR)has been shown to be a good treatment option for the management of nonpedunculated polyps≥10 mm since its introduction.However,there is a paucity of randomized controlled trials(RCTs)in Asia.AIM To compare the efficacy and safety of UEMR with those of conventional EMR(CEMR)in treating nonpedunculated colorectal lesions.METHODS We carried out this RCT at a tertiary hospital from October 2022 to July 2024.Patients with nonpedunculated colorectal neoplasms ranging from 10 mm to 30 mm in size were randomly assigned to either the UEMR or CEMR group.The primary outcome was the curative resection(R0)rate.The secondary outcomes included en bloc resection,procedure time,adverse events,and the number of clips used for defect closure.RESULTS A total of 260 patients with 260 lesions(130 in each UEMR and CEMR group)were recruited.The median age was 58(27-85)years,the male/female ratio was 1.74,and the median lesion size was 20(10-30 mm)mm.Compared with CEMR,UEMR was associated with a significantly greater curative resection(R0)rate(98.4%vs 90.3%;P=0.007),greater en bloc resection rate(100%vs 94.6%;P=0.014),shorter procedure time(65 vs 185 seconds;P<0.001),lower rate of bleeding complications(1.5%vs 10%;P=0.003),and fewer clips used(2 vs 3;P<0.001).No perforations were observed in either group.CONCLUSION Compared with CEMR,UEMR has a higher R0 rate,greater en bloc resection rate,shorter procedure time,fewer bleeding complications,and clips used in the management of nonpedunculated colorectal neoplasms.展开更多
文摘Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.
文摘Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.
文摘Selective internal radiation therapy using yttrium-90 has been used to treat hepatocellular carcinoma,intrahepatic cholangiocarcinoma,and other malignant tumors that have spread to the liver locally.The authors used the bibliometric approach in response to the neoplasms,using the keyword“Yttrium 90 AND Liver Neoplasms”as a search parameter and then looked up pertinent English-language literature in the Web of Science core collection database’s selfbuilt database through November 30,2025.For statistical analysis and literature management,EndNote and Excel tools were utilized.In addition to co-citation and emergent keyword analysis of authors,VOSviewer and CiteSpace were utilized for social network and chronological order of countries,institutions,authors,and keywords.The aim of this study was to serve as a reference for future research by methodically sorting through the international research literature on Yttrium 90 treatment of liver neoplasms and summarizing the research status and hot trends in this field.In recent years,research focus has increasingly shifted toward high-quality,multi-center clinical trials that combine SIRT-targeted systemic therapy with hepatectomy following the descending stage.This approach is likely to remain a significant research trend in the field.
基金supported by the National Natural Science Foundation of China(No.52388102)the Sichuan Science and Technology Program(No.2024NSFTD0011)the Fundamental Research Funds for the State Key Laboratory of Rail Transit Vehicle System of Southwest Jiaotong University(No.2023TPL-T11).
文摘The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.
基金supported by the National Natural Science Foundation of China(Grant Nos.42407267 and 52374152)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20220975).
文摘Time-delayed blasting is widely utilized in engineering to mitigate induced vibration hazards and enhance fragmentation.The underlying vibration reduction principle is the decrease of the charge weight per delay,while the potential for further vibration reduction remains debated,largely due to unclear underlying mechanisms.In light of the popularization of electronic detonators and the representativeness of double-hole configurationsfor multiple blastholes,it is essential to investigate the vibration characteristics induced by time-delayed double blastholes.Therefore,a series of doubleborehole experimental blasts was conducted in an underground roadway to clarify the variation in vibration from single-hole to dual-hole conditions.Based on the experimental data and inherent limitations,an exact full-fieldtheoretical model was further employed to systematically analyze the effects of delay time,charge length,and borehole inclination angle on vibrations induced by various doublehole configurations.The experimental data and theoretical analysis reveal that the general scaled distance effectively predicts vibrations in delayed blasting but does not reflectvibration reduction.Increasing delay time causes fluctuatingPPVs,which stabilize slightly above single-hole PPVs as delay times exceed a certain value.The delayed blasting primarily reduces near-fieldfrequencies.Longer charge lengths in double boreholes increase PPV levels and attenuation rates within a certain length,and the vibration behavior of combined long and short charge lengths is governed by the long blasthole.Larger blasthole inclination angles enhance vibration amplitude and reduce PPV attenuation rates.Optimizing inclination angles is more critical than adjusting delay times,and parallel boreholes offer the best vibration control.
基金Ministry of Research,Innovation and Digitization,CCCDI-UEFISCDI,Grant/Award Number:PN-IV-P7-7.1-PED-2024-1578,within PNCDI Ⅳ.
文摘Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.
基金Science and Technology Planning Project of Guangdong Province,2023B1212060048,Xiande Xie。
文摘Recovered samples of Jilin H5 chondrite experimentally shocked to 12-133 GPa were studied to explore the behavior of opaque minerals under shock loading using SEM-EDS,Raman spectroscopy,and TIMA.The following results were obtained.Firstly,at pressures lower than 53GPa,the opaque minerals still keep the unmelted state,while at 78 GPa and higher,FeNi metal and troilite form eutectic intergrowths occurring as disorderly fine veinlets filling the shock-induced fractures in silicate minerals.Secondly,single kamacite grains still maintain their contour at 12 GPa,but a part of brittle troilite grains was fragmented and squeezed into the shock-induced fractures within kamacite grains.At53 and 133 GPa,many more troilite fragments are poured in the kamacite interior to form disordered hybrid aggregates or to form squiggly strips,respectively.Similar phenomena are observed within single troilite grains,but the mineral squeezed into troilite grains is kamacite.Thirdly,chromite is a hard and refractory oxide mineral.When the shock pressure rises step by step from 12 to 133 GPa,the shock effect of chromite is only fragmentation.Its grain size decreases from tens of um at 53 GPa to a few um at 133 GPa.And,fourthly,native copper exhibits distinct redistribution behavior at high temperature.In Jilin samples shock-loaded to 12 GPa,copper initially located at troilite-kamacite interfaces partially transferred into small troilite grains containing fine FeNi particles.At 53 and 133 GPa,native copper preferentially transferred into larger troilite grains containing more particles of eutectic FeNi metal.
基金Supported by Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9,Yuejiao Gao Han[2024]No.30)Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)+1 种基金Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)Quality Engineering and Teaching Reform Projects of Zhaoqing University(zlgc202239,zlgc202207,zlgc2024005,zlgc2024038).
文摘To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.
基金financial support pro-vided by National Natural Science Foundation of China(Grant No.52178402).
文摘The shear adhesive strength at the clay‒metal interfaces serves as a critical parameter for evaluating the soil adhesion and metal interface mudding phenomena.However,its rapid determination remains challenging because of the demanding requirements for high-precision instrumentation and complex calibration procedures.In this study,an integrated framework was presented that combined physical experiments,theoretical approaches,and machine learning to enable the autonomous determination of the shear adhesive strength of soil under multiple influencing factors.We developed an improved particle swarm optimization-optimized ordinary kriging(IPOK)surrogate testing method to enhance the limited experimental datasets,and a lightweight residual neural network(RLNet)was then used for effective intra-and extra-domain predictions.A comprehensive model discussion,comparison,and interpretability analysis were conducted.The results from 64 physical experiments considering the consistency index,normal stress,clay content,rotation rate,and disc material effectively characterized the shear adhesion behaviour of kaolin.The IPOK surrogate experiments successfully replicated the physical data points while enriching the dataset details.The RLNet model trained with IPOK data achieved superior prediction performance,with a root mean square error of 7.491 and a determination coefficient of 0.927 in 16 orthogonal validation tests,and high similarity was attained between the predicted and measured values.A detailed model discussion analysis confirmed the superiority of the IPOK-RLNet framework.This methodology provides a cost-effective rapid analysis technique for assessing clay‒metal interface shear adhesion,significantly reducing laboratory testing requirements and experimental costs while increasing engineering efficiency.
文摘Appendiceal mucinous neoplasms(AMNs)are rare tumors originating from mucin-producing epithelial cells of the appendix.They can exhibit both benign and malignant behavior.They are often incidentally discovered during appendectomy.Clinical presentation ranges from asymptomatic to mimicking acute appendicitis.Histologically,noninvasive AMNs are classified as low-grade AMNs(LAMNs)or high-grade AMNs(HAMNs),whereas invasive tumors are categorized as mucinous adenocarcinomas.Although LAMNs and HAMNs are generally nonmalignant,rupture can lead to pseudomyxoma peritonei(PMP).Surgical resection is the primary diagnostic and therapeutic approach,with intraoperative assessment to prevent rupture.Treatment strategies vary based on findings and include appendectomy,right hemicolectomy,and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.Histological diagnosis relies on mucin detection,and immunohistochemical markers such as cytokeratin 20(diffusely positive),cytokeratin 7(often negative),mucin 5AC,and special ATrich sequence-binding protein 2 assist in characterization.Molecular profiling frequently identifies KRAS,GNAS,and TP53 mutations.KRAS mutations are generally associated with a favorable prognosis,whereas GNAS and TP53 mutations correlate with poorer survival outcomes.These findings highlight the potential role of molecular profiling in guiding treatment strategies for AMN and PMP.
基金supported by the National Natural Science Foundation of China(82104596)the Shenzhen Key Medical Discipline Construction Fund&Sanming Project of Medicine in Shenzhen(SZSM202111002)+1 种基金the Medicine-Engineering Interdisciplinary Research Foundation of Shenzhen University(2023YG019)the Shenzhen Science and Technology Program(GJHZ20220913143005010)。
文摘Neuroendocrine neoplasms(NENs)are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system.Gastroenteropancreatic NENs(GEP-NENs)are the most common subtype of NENs.Historically,GEP-NENs have been regarded as infrequent and slow-growing malignancies;however,recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades.In addition,an increasing number of studies have proven that GEP-NENs result in a limited life expectancy.These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed.Therefore,there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs.In this review,we have summarized the limitations and recent advancements in our comprehension of the epidemiology,clinical presentations,pathology,molecular biology,diagnosis,and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.
文摘To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].
文摘BACKGROUND Pancreatic cystic neoplasms(PCNs)are increasingly detected due to advancements in radiographic techniques,with a prevalence of approximately 15%in the general population.These lesions range from benign to premalignant and malignant,posing a diagnostic challenge.Accurate differentiation is critical,as premalignant and malignant PCNs often require surgical intervention,while benign cysts may only need monitoring unless symptomatic.Current diagnostic methods,including cross-sectional imaging,endoscopic ultrasonography,and endoscopic ultrasonography-guided fine-needle aspiration/biopsy,are specialized,not universally available,and have variable accuracy.Clinical and laboratory parameters such as carbohydrate antigen 19-9(CA 19-9),neutrophillymphocyte ratio,platelet-lymphocyte ratio,and red cell distribution width(RDW)have been associated with malignancy risk,though only CA 19-9 is guideline-supported.AIM To assess the malignancy risk of PCNs using preoperative clinical and routine laboratory parameters.METHODS A retrospective cohort study analyzed 70 patients who underwent surgery for PCNs at Ankara Bilkent City Hospital between February 2019 and March 2023.Patients were categorized into group A(benign or low-grade dysplasia,n=40)and group B(malignancy or high-grade dysplasia,n=30)based on postoperative pathology.Preoperative demographic and laboratory parameters,including age,RDW,albumin,and CA 19-9,were compared.Univariate and multivariate logistic regression analyses identified independent predictors of malignancy.Receiver operating characteristic curve analysis evaluated predictive performance,with internal validation using bootstrapping.RESULTS Group B patients were older(69.86±9.58 years vs 52.74±16.85 years,P<0.001)and had a higher incidence of diabetes mellitus(57.1%vs 21.4%,P=0.002).RDW(16.2%vs 13.7%,P<0.001),platelet-lymphocyte ratio(178 vs 126,P=0.008),and CA 19-9(21.7 U/mL vs 9.3 U/mL,P=0.009)were significantly higher in group B,while albumin was lower(41 g/L vs 45 g/L,P=0.008).Multivariate analysis identified age[odds ratio=1.067,95%confidence interval(CI):1.014-1.122,P=0.012]and RDW(odds ratio=1.784,95%CI:1.172-2.715,P=0.007)as independent predictors.The area under the curve for age,RDW,and their combination was 0.798(95%CI:0.695-0.900),0.801(95%CI:0.692-0.911),and 0.858(95%CI:0.771-0.944),respectively,with bootstrapped validation confirming stability.Cut-off values of age≥60 years and RDW≥15.5%balanced sensitivity and specificity,increasing malignancy risk 15.3-fold and 22.6-fold,respectively.CONCLUSION Age and RDW are independent predictors of malignancy in PCNs,aiding in patient selection for advanced diagnostics and surgery.Larger,multicenter studies are needed to validate these findings.
基金supported by the National Natural Science Foundation of China (Nos.30925033,30801101,and 81171884)the Innovation and High-Level Talent Training Program of Department of Health of Zhejiang Province,China
文摘Pancreatic cystic neoplasms(PCNs) are a diverse group of neoplasms in the pancreas,and are more increasingly encountered with widespread abdominal screening and improved imaging techniques.The most common types of PCNs are serous cystic neoplasms(SCNs),mucinous cystic neoplasms(MCNs),and intraductal papillary mucinous neoplasms(IPMNs).Clinicians frequently feel bewildered in the differential diagnosis and subsequent management among the various types of lesions in the pancreas,which may lead to overtreatment or delayed treatment.The current review provides recent developments in the understanding of the three most common types of PCNs,the latest modalities used in preoperative diagnosis and differential diagnosis,as well as the most up to date management.Suggestions for diagnosis and differential diagnosis of SCNs,MCNs,and IPMNs are also provided for young surgeons.Better understanding of these neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients.
文摘Neuroendocrine neoplasms(NENs)are relatively rare tumors that arise from peptidergic neurons and neuroendocrine cells.NENs are highly heterogeneous and can occur in any part of the body,with a particular prevalence in the digestive system.NENs consist of a range of tumor types and the biological behaviors exhibit significant differences.NENs are classified into well-differentiated neuroendocrine tumors(NETs)and poorly differentiated neuroendocrine carcinomas(NECs).NETs can be further classified and graded into the following three categories:low-grade NETs,grade 1(NET G1);intermediate-grade NET G2;and high-grade NET G3.NECs include large cell-type NEC(LCNEC)and small cell-type NEC(SCNEC),both of which are considered high grade.Currently,the main treatments for advanced NENs are biological treatments,targeted therapy,chemotherapy,and newer treatments that are still under development,such as immunotherapy and peptide receptor radionuclide therapy(PRRT).However,owing to the rarity of NENs,pharmaceutical company investment is limited and few phase Ⅲ studies have targeted advanced NENs.Most current research consists of investigator-initiated phase Ⅰ and Ⅱ clinical trials or largescale retrospective studies.NEN treatment should be chosen carefully because it is cumbersome and complicated,as indicated above.Herein,we comprehensively summarize the clinical application status and research progress for advanced NEN treatment regimens,especially for advanced NETs,which may help to create awareness on NENs among medical professionals across specialties.
基金United Arab Emirates University,Grant/Award Number:12R104 and 12R121。
文摘Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金Supported by National Natural Science Foundation of China,No.82004298Jiangsu Graduate Research and Practice Innovation Program,China,No.KYCX23_2090.
文摘BACKGROUND Recently,several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms(R-NENs).However,none of these methods can achieve 100%complete resection(CR),particularly in the vertical direction.Endoscopic full-thickness resection(EFTR)has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs.AIM To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique.METHODS This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs,including 132 who underwent endoscopic submucosal dissection(ESD)and 28 who underwent EFTR.Lesions were categorized as<1 cm,1-2 cm,and>2 cm in size.CR rate,en bloc resection rate,operation time,and complications were evaluated.Subgroup analyses and follow-up were also performed.RESULTS EFTR achieved 100%CR rates for lesions<1 cm and 1-2 cm,compared with 67.0%and 50.0%,respectively,in the ESD group.En bloc resection and successful removal of the R-NENs were achieved in all patients.Meanwhile,EFTR showed performance comparable to ESD in terms of operation time,hospitalization cost,and postoperative adverse events,except for a one-day longer hospital stay.We also analyzed the invasion depth of R-NENs based on full-thickness specimens.The data showed that 80%of lesions(<1 cm)and 85.7%of lesions(1-2 cm)had invaded the SM3 level or deeper at the time of resection.For ESD specimens,46.6%(<1 cm)and 89.3%(1-2 cm)of lesions had infiltrated more than 2000μm beneath the muscularis mucosae.CONCLUSION EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.
基金Shanghai Clinical Research Center for Chronic Musculoskeletal Diseases (20MC1920600)Shanghai Key Clinical Specialty "Traditional Chinese Medicine Orthopaedic Traumatology"(shslczdzk03901)+3 种基金The Second Round of Construction Project of National TCM Academic School Inheritance Studio "Shi's Trauma Department"[Letter of the People's Education of Traditional Chinese Medicine (2019) No.62]Shanghai High-level Local Universities "Chronic Muscle and Bone Damage Research and Transformation" Innovation Team [No.3 of Shanghai Education Commission (2022)]Program for Shanghai High-Level Local University Innovation Team (SZY20220315)Shanghai Shenkang Hospital Development Center Clinical Three-year Action Plan (SHDC2020CR3090B)。
文摘OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.
文摘BACKGROUND Underwater endoscopic mucosal resection(UEMR)has been shown to be a good treatment option for the management of nonpedunculated polyps≥10 mm since its introduction.However,there is a paucity of randomized controlled trials(RCTs)in Asia.AIM To compare the efficacy and safety of UEMR with those of conventional EMR(CEMR)in treating nonpedunculated colorectal lesions.METHODS We carried out this RCT at a tertiary hospital from October 2022 to July 2024.Patients with nonpedunculated colorectal neoplasms ranging from 10 mm to 30 mm in size were randomly assigned to either the UEMR or CEMR group.The primary outcome was the curative resection(R0)rate.The secondary outcomes included en bloc resection,procedure time,adverse events,and the number of clips used for defect closure.RESULTS A total of 260 patients with 260 lesions(130 in each UEMR and CEMR group)were recruited.The median age was 58(27-85)years,the male/female ratio was 1.74,and the median lesion size was 20(10-30 mm)mm.Compared with CEMR,UEMR was associated with a significantly greater curative resection(R0)rate(98.4%vs 90.3%;P=0.007),greater en bloc resection rate(100%vs 94.6%;P=0.014),shorter procedure time(65 vs 185 seconds;P<0.001),lower rate of bleeding complications(1.5%vs 10%;P=0.003),and fewer clips used(2 vs 3;P<0.001).No perforations were observed in either group.CONCLUSION Compared with CEMR,UEMR has a higher R0 rate,greater en bloc resection rate,shorter procedure time,fewer bleeding complications,and clips used in the management of nonpedunculated colorectal neoplasms.