BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of ...BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.展开更多
Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal ce...Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.展开更多
This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patient...This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patients with familial GISTs.The actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some GISTs.The molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha(PDGFRA)genes.A subset of GISTs without these mutations known as wild-type GISTs,may harbor other rare mutations,impacting their response to targeted therapies.Clinically,patients with GISTs present with nonspecific symptoms,often leading to delayed diagnosis.Genetic predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of GISTs.Management has evolved from surgical interventions to molecular-based therapies using tyrosine kinase inhibitors.The management of GISTs,especially in familial cases,requires a multidisciplinary approach.Cases of different gene mutations were reported in the same family,suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.展开更多
Objective:There is currently no consensus on whether extra-gastrointestinal stromal tumors(EGISTs)and gastrointestinal stromal tumors(GISTs)are the same type of tumor,and whether the diagnosis and treatment of EGISTs ...Objective:There is currently no consensus on whether extra-gastrointestinal stromal tumors(EGISTs)and gastrointestinal stromal tumors(GISTs)are the same type of tumor,and whether the diagnosis and treatment of EGISTs can directly replicate the current diagnostic and treatment standards for GISTs.This study aims to further elucidate the clinical and pathological characteristics,diagnosis,treatment,and prognosis of EGISTs by analyzing the research results of domestic scholars in the field of EGISTs in the past decade.Methods:A review was conducted on original Chinese and English research articles published from 2013 to 2022 focusing on EGISTs.A descriptive approach was used to extract key information from the literature,including patient demographics,tumor location,tumor diameter,mitotic figures,risk stratification,immunohistochemical markers,cell type,and prognostic factors.The data were subjected to statistical analysis.Results:A total of 12 articles containing 780 EGIST patients were included.The male-to female incidence of EGISTs was 0.92꞉1.The most common sites of EGISTs were mesentery(30.96%),peritoneum or retroperitoneum(28.53%),omentum(20.32%),and pelvic cavity(12.52%).52.77%of EGISTs had tumor diameters greater than 10 cm,and the proportions of EGISTs with nuclear fission patterns greater than 5/50 high power field(HPF)and greater than 10/50 HPF were 51.24%and 26.11%,respectively.The proportion of high-risk EGISTs was 79.05%.The positive rates of immune markers CD117,CD34,and DOG-1 in EGISTs were 82.3%,69.0%,and 79.5%,respectively.The proportion of Ki-67>5%was 49.2%,and the proportion of Ki-67>10%was 24.8%.The proportions of EGISTs in spindle cells,epithelial cells,and mixed cells were 74.4%,14.8%,and 13.1%,respectively.The diameter of the tumor,resection method,risk level,Ki-67 index,mitotic counts,presence of rupture/bleeding/necrosis/peripheral tissue invasion/recurrence and metastasis,as well as the use of imatinib treatment after surgery were important factors affecting the prognosis of EGISTs.Conclusion:Current medical research is relatively well cognizant of GISTs with primary sites in the gastrointestinal tract.Compared with GISTs,EGISTs have large tumor diameters,high mitotic counts,a high percentage of high-risk grades,relatively unique molecular expression,and high aggressiveness.EGISTs differ from GISTs in clinicopathological characteristics.Whether EGISTs and GISTs share a common origin remains unclear.If they are distinct tumor entities,separate diagnostic and treatment guidelines for EGISTs should be established.If EGISTs are ultimately confirmed to be a special subtype of GISTs,then directly applying existing GIST-based standards to EGISTs may be inappropriate.A more scientific approach would involve subclassifying EGISTs based on anatomical location and then tailoring treatment strategies accordingly with reference to GIST guidelines.展开更多
Oesophageal gastrointestinal stromal tumours are rare,anatomically challenging lesions with higher surgical morbidity than their gastric counterparts.Emerging endoscopic resection techniques such as endoscopic submuco...Oesophageal gastrointestinal stromal tumours are rare,anatomically challenging lesions with higher surgical morbidity than their gastric counterparts.Emerging endoscopic resection techniques such as endoscopic submucosal dissection and submucosal tunnelling endoscopic resection show much promise for the management of patients who are not fit for,or wish to avoid the morbidity of,major surgical resection.These techniques require careful patient selection and advanced technical skills.We build on the recent review of such techniques by Vogli et al.Current evidence is limited to small case series with heterogeneity in patient selection,tumor size,and outcomes.Notably,long-term oncological data remain sparse,and complications such as bleeding or perforation may be life-threatening in patients unfit for surgical rescue.Nonetheless,endoscopic approaches have many potential advantages to offer such as preserved quality of life and definitive management of unfit patients.展开更多
BACKGROUND Ovarian sclerosing stromal tumors(OSSTs)are found most commonly in females at 20-30 years of age.They can also occur at any point during pre-puberty,puberty,or menopause.Clinical manifestations of OSSTs inc...BACKGROUND Ovarian sclerosing stromal tumors(OSSTs)are found most commonly in females at 20-30 years of age.They can also occur at any point during pre-puberty,puberty,or menopause.Clinical manifestations of OSSTs include abdominal pain,an abdominal mass,menstrual abnormalities,and infertility.Infrequently,patients will experience androgen-related manifestations of masculinization,such as increased hair,acne,or a low voice.Diagnosis must be confirmed by immunohistochemical analysis of the tissue as clinical symptoms and imaging studies are unreliable.CASE SUMMARY A 14-year-old female presented with amenorrhea.After a thorough medical examination,endocrine and tumor markers analysis,and imaging,a pelvic mass was discovered.The patient also exhibited endocrine dysfunction but was not positive for any tumor markers.The patient underwent surgery to remove the ovarian tumor.Immunohistochemical analysis of the resected specimen indicated an OSST.During the postoperative follow-up,the patient had attained menarche.CONCLUSION This case’s clinical manifestation of endocrine dysfunction due to OSST provides new insights that will assist clinicians in the diagnosis and treatment of this common tumor.展开更多
In this paper,we comment on the article by Gu et al published in 2024,invest-igating whether there were differences in the clinical/perioperative outcomes of endoscopic and laparoscopic resections of gastric stromal t...In this paper,we comment on the article by Gu et al published in 2024,invest-igating whether there were differences in the clinical/perioperative outcomes of endoscopic and laparoscopic resections of gastric stromal tumors.Compared with most carcinomas,gastrointestinal stromal tumors are quite common worldwide and have a better prognosis.However,they respond to specific chemotherapies and do not routinely require standard lymphadenectomy.The gastric origin is known to be the most represented.Survival after proven radical surgery is ex-cellent,with recurrences being extremely infrequent.Currently,induction/pe-rioperative chemotherapy for high-risk tumors larger than 5 cm can downstage neoplasia and maintain good survival.Therefore,the standard of care for non-metastatic,resectable tumors is surgical excision(avoiding formal lymphaden-ectomy)with or without chemotherapy.In the case of small-(2 cm)to medium-(5 cm)sized tumors,minimally invasive surgical approaches(laparoscopic or ro-botic)have been advocated,and more recently,a purely endoscopic technique has also been proposed.All these interventions are feasible and effective,although no definitive results have been published to prove the superiority of one over another;however,further investigation of its associated oncologic outcomes is still needed.Unfortunately,rigorous,prospective,randomized controlled trials are challenging to conduct,develop,and receive ethical approval for,whereas the final decision of the surgical route is often related to the availability of instru-mentation and local expertise.展开更多
While rare,esophageal gastrointestinal stromal tumors(GISTs)have higher mali-gnant potential and are typically diagnosed at larger sizes compared to gastric GISTs.However,well-defined guidelines for their optimal mana...While rare,esophageal gastrointestinal stromal tumors(GISTs)have higher mali-gnant potential and are typically diagnosed at larger sizes compared to gastric GISTs.However,well-defined guidelines for their optimal management remain lacking.Most esophageal GISTs are surgically managed with enucleation,while esophagectomy is reserved for larger tumors.Recent advances in endoscopic techniques,such as endoscopic submucosal dissection and submucosal tunneling endoscopic resection(ER),have allowed for endoscopic removal of submucosal esophageal lesions,including GISTs.Xu et al reported on the clinical and on-cological outcomes of 32 patients with esophageal GISTs treated with ER.The study demonstrated high en bloc resection rates and favorable 5-year overall survival and disease-free survival.However,it primarily focused on small,inci-dentally detected GISTs,with 75%of cases classified as very low or low risk according to the National Institutes of Health criteria.The authors favored the submucosal tunneling ER technique despite its procedural challenges in the upper esophagus.In this editorial,we briefly discuss the advantages and limitations of endoscopic techniques compared to surgical approaches.We also emphasize the need to establish specific management criteria for submucosal esophageal lesions to guide clinical practice.展开更多
Heart failure(HF)is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood.Currently,HF remains a leading cause of morbidity and mortality worldwide,imposing a substant...Heart failure(HF)is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood.Currently,HF remains a leading cause of morbidity and mortality worldwide,imposing a substantial burden on global healthcare systems.Recent advancements have highlighted the therapeutic potential of mesenchymal stromal cells(MSCs)in managing HF.Notably,umbilical cord-derived MSCs(UC-MSCs)have demonstrated superior clinical potential compared to traditional bone marrow-derived MSCs;this is evident in their non-invasive collection process,higher proliferation efficacy,and lower immunogenicity and tumorigenicity,as substantiated by preclinical studies.Although the feasibility and safety of UC-MSCs have been tested in animal models,the application of UC-MSCs in HF treatment remains challenged by issues such as inaccurate targeted migration and low survival rates of UC-MSCs.Therefore,further research and clinical trials are imperative to advance the clinical application of UC-MSCs.展开更多
In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of M...In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.展开更多
BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteri...BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteristics and clinical results of oesophageal GISTs.AIM To investigate endoscopic treatment effective of oesophageal GISTs.METHODS It was retrospective research that collected 32 patients with oesophageal GISTs treated by endoscopic resection(ER)between January 2012 and January 2023 in two Hospital.Clinicopathologic,endoscopic records,and follow-up data were collected and analysed.RESULTS Thirty-one patients underwent en bloc resection and 24(75.0%)lesions underwent R0 resection.The size of GISTs was 2.12±1.88 cm.The overall complication rate was 25.0%,including hydrothorax and post-endoscopic submucosal dissection electrocoagulation syndrome.The mean mitotic index was 3.34±5.04(median,1.50;range,1.00-4.00).Eighteen(56.3%),6(18.8%),2(6.3%),and 6(18.8%)patients were identified as very low,low,intermediate,and high risk,respectively.Three patients developed recurrence after a median follow-up of 64.69±33.13 months.The 5-year overall survival rate was 100%,and the disease-free survival rate was 90.6%.CONCLUSION ER is safe and effective for patients with low-risk oesophageal GISTs.Early detection of oesophageal GISTs is essential to achieve a favourable prognosis.展开更多
Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative medicine.However,while MSCs have been shown to b...Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative medicine.However,while MSCs have been shown to be safe as a cellular treatment,they have usually been therapeutically ineffective in human diseases.In fact,in many clinical trials it has been shown that MSCs have moderate or poor efficacy.This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs.Recently,specific priming strategies have been used to improve the therapeutic properties of MSCs.In this review,we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs.We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes.Particularly,while hypoxic priming can be used primarily for the treatment of acute diseases,inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders.The shift in approach from regeneration to inflammation implies,in MSCs,a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways.The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.展开更多
Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a pro...Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated wit...BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated with neurofibromatosis type 1(NF1),an autosomal dominant genetic disease resulting from pathogenic mutations in the NF1 gene,which encodes the neurofibromin protein.NF1 patients often exhibit multi-system involvement,with café-au-lait macules and neurofibromas being characteristic symptoms.GISTs are a rare complication of NF1,with the tumors most frequently occurring in the small intestine(90%of cases),while occurrences in the stomach are rare.CASE SUMMARY A 51-year-old woman presented to the emergency department with complaints of dizziness,fatigue,chest tightness,and dark stools.Initial examination revealed a red blood cell count of 1.99×1012/L and a hemoglobin level of 43 g/L.She underwent blood transfusions and fluid replacement to stabilize her condition.Further investigations identified typical café-au-lait macules on her trunk,limbs,and face,along with neurofibromas.Endoscopy showed coffee-colored fluid in the gastric cavity,a large submucosal elevation with an exudative covering,and ulcer formation on the gastric fundus.Exploratory laparoscopy confirmed the tumor’s origin in the gastric fundus,and resection of the giant GIST was performed.Pathological analysis revealed a necrotic GIST measuring 18 cm×14 cm,classified as high-risk,with approximately 5 mitotic figures per 10 high-power fields and no tumor at the margins.Immunohistochemistry results were CD117(+),delay of germination 1(+),CD34(+),and succinate dehydrogenase complex iron sulfur subunit B intact expression.Genetic testing using next-generation sequencing confirmed an NF1 gene mutation.The patient underwent successful tumor resection and was discharged home with postoperative regorafenib therapy.A follow-up at one year showed no recurrence.CONCLUSION Given the diversity of clinical symptoms associated with NF1 and the complexity of NF1-related GISTs,surgical resection with complete tumor removal remains the preferred treatment option.However,the absence of a standardized treatment protocol for adjuvant therapy presents numerous challenges for clinicians.展开更多
OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pat...OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.展开更多
Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the mul...Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.展开更多
BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.展开更多
Decisions regarding the management of patients with esophageal gastrointestinal tumors(EGISTs)are very challenging,as there are still no clear guidelines on the treatment of these tumors due to their rarity.Surgery re...Decisions regarding the management of patients with esophageal gastrointestinal tumors(EGISTs)are very challenging,as there are still no clear guidelines on the treatment of these tumors due to their rarity.Surgery remains the standard treatment,but it is known that surgical procedures performed on the esophagus are related to a high risk of serious postoperative complications and impaired quality of life.Endoscopic resection is both safe and effective for patients with low-risk EGISTs.This article presents the current therapeutic options in patients with EGISTs,including both the endoscopic and surgical approach,and discusses the results,strengths and limitations of the recent article by Xu et al regarding the endoscopic treatment outcome of EGISTs.展开更多
Zhao et al’s investigation on the assessment of inflammatory markers prognostic value for relapse-free survival in patients with gastrointestinal stromal tumor(GIST)using a nomogram-based approach is a scientific app...Zhao et al’s investigation on the assessment of inflammatory markers prognostic value for relapse-free survival in patients with gastrointestinal stromal tumor(GIST)using a nomogram-based approach is a scientific approach.This study explored the potential of an inflammatory marker-based nomograph model,highlighting the relapse-free survival-associated risk factors prognostic potential in patients with GIST.The author assessed 124 samples from patients with GIST to find an association between inflammatory markers and tumor size in a retrospective study using multivariate regression analysis.Further,a nomogram model was developed to identify the independent risk factors for the prognosis.GIST clinical treatment can use preoperative monocyte/lymphocyte ratio and platelet/lymphocyte ratio for relapse-free survival prognosis as independent factors.展开更多
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms primarily originating in the stomach or small intestine.Duodenal GISTs are particularly uncommon,accounting for only a small fraction of GIST cases.These tumors often present with nonspecific symptoms,making early detection challenging.This case discusses a duodenal GIST misdiagnosed as pancreatic cancer due to obstructive jaundice.CASE SUMMARY A 40-year-old male with jaundice and abdominal symptoms underwent imaging,which suggested a malignant periampullary tumor.Preoperative misdiagnosis of pancreatic cancer was made,and surgery was performed.Postoperative histopathology confirmed a duodenal GIST.The role of artificial intelligence in the diagnostic pathway is explored,emphasizing its potential to differentiate between duodenal GISTs and other similar conditions using advanced imaging analysis.CONCLUSION Artificial intelligence in radiomic imaging holds significant promise in enhancing the diagnostic process for rare cancers like duodenal GISTs,ensuring timely and accurate treatment.
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
基金the Scientific and Technological Research Council of Türkiye(TÜBİTAK)Under the International Postdoctoral Research Fellowship Program(2219),No.1059B192400980the National Postdoctoral Research Fellowship Program(2218),No.122C158.
文摘Acute respiratory distress syndrome(ARDS)is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options.Notably,Zhang et al demonstrated that CD146+mesenchymal stromal cells(MSCs)exhibited greater therapeutic efficacy than CD146-MSCs.These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors.We concur that MSCs hold significant promise for ARDS treatment;however,the heterogeneity of cell products is a translational barrier.Phenotype-aware strategies,such as CD146 enrichment,standardized potency assays,and extracellular vesicle profiling,are essential for improving the consistency of these studies.Further-more,advanced preclinical models,such as lung-on-a-chip systems,may provide more predictive insights into the therapeutic mechanisms.This article underscores the importance of CD146+MSCs in ARDS,emphasizes the need for precision in defining cell products,and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.
基金National Natural Science Foundation of China,No.82370569Basic and Applied Basic Research Foundation of Guangdong Province,No.2022A1515012647the Key Program for Science and Technology Projects of Social Development in Zhuhai,No.2220004000249(to Li XF).
文摘This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patients with familial GISTs.The actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some GISTs.The molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha(PDGFRA)genes.A subset of GISTs without these mutations known as wild-type GISTs,may harbor other rare mutations,impacting their response to targeted therapies.Clinically,patients with GISTs present with nonspecific symptoms,often leading to delayed diagnosis.Genetic predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of GISTs.Management has evolved from surgical interventions to molecular-based therapies using tyrosine kinase inhibitors.The management of GISTs,especially in familial cases,requires a multidisciplinary approach.Cases of different gene mutations were reported in the same family,suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.
基金supported by the National Natural Science Foundation(81960508)。
文摘Objective:There is currently no consensus on whether extra-gastrointestinal stromal tumors(EGISTs)and gastrointestinal stromal tumors(GISTs)are the same type of tumor,and whether the diagnosis and treatment of EGISTs can directly replicate the current diagnostic and treatment standards for GISTs.This study aims to further elucidate the clinical and pathological characteristics,diagnosis,treatment,and prognosis of EGISTs by analyzing the research results of domestic scholars in the field of EGISTs in the past decade.Methods:A review was conducted on original Chinese and English research articles published from 2013 to 2022 focusing on EGISTs.A descriptive approach was used to extract key information from the literature,including patient demographics,tumor location,tumor diameter,mitotic figures,risk stratification,immunohistochemical markers,cell type,and prognostic factors.The data were subjected to statistical analysis.Results:A total of 12 articles containing 780 EGIST patients were included.The male-to female incidence of EGISTs was 0.92꞉1.The most common sites of EGISTs were mesentery(30.96%),peritoneum or retroperitoneum(28.53%),omentum(20.32%),and pelvic cavity(12.52%).52.77%of EGISTs had tumor diameters greater than 10 cm,and the proportions of EGISTs with nuclear fission patterns greater than 5/50 high power field(HPF)and greater than 10/50 HPF were 51.24%and 26.11%,respectively.The proportion of high-risk EGISTs was 79.05%.The positive rates of immune markers CD117,CD34,and DOG-1 in EGISTs were 82.3%,69.0%,and 79.5%,respectively.The proportion of Ki-67>5%was 49.2%,and the proportion of Ki-67>10%was 24.8%.The proportions of EGISTs in spindle cells,epithelial cells,and mixed cells were 74.4%,14.8%,and 13.1%,respectively.The diameter of the tumor,resection method,risk level,Ki-67 index,mitotic counts,presence of rupture/bleeding/necrosis/peripheral tissue invasion/recurrence and metastasis,as well as the use of imatinib treatment after surgery were important factors affecting the prognosis of EGISTs.Conclusion:Current medical research is relatively well cognizant of GISTs with primary sites in the gastrointestinal tract.Compared with GISTs,EGISTs have large tumor diameters,high mitotic counts,a high percentage of high-risk grades,relatively unique molecular expression,and high aggressiveness.EGISTs differ from GISTs in clinicopathological characteristics.Whether EGISTs and GISTs share a common origin remains unclear.If they are distinct tumor entities,separate diagnostic and treatment guidelines for EGISTs should be established.If EGISTs are ultimately confirmed to be a special subtype of GISTs,then directly applying existing GIST-based standards to EGISTs may be inappropriate.A more scientific approach would involve subclassifying EGISTs based on anatomical location and then tailoring treatment strategies accordingly with reference to GIST guidelines.
文摘Oesophageal gastrointestinal stromal tumours are rare,anatomically challenging lesions with higher surgical morbidity than their gastric counterparts.Emerging endoscopic resection techniques such as endoscopic submucosal dissection and submucosal tunnelling endoscopic resection show much promise for the management of patients who are not fit for,or wish to avoid the morbidity of,major surgical resection.These techniques require careful patient selection and advanced technical skills.We build on the recent review of such techniques by Vogli et al.Current evidence is limited to small case series with heterogeneity in patient selection,tumor size,and outcomes.Notably,long-term oncological data remain sparse,and complications such as bleeding or perforation may be life-threatening in patients unfit for surgical rescue.Nonetheless,endoscopic approaches have many potential advantages to offer such as preserved quality of life and definitive management of unfit patients.
文摘BACKGROUND Ovarian sclerosing stromal tumors(OSSTs)are found most commonly in females at 20-30 years of age.They can also occur at any point during pre-puberty,puberty,or menopause.Clinical manifestations of OSSTs include abdominal pain,an abdominal mass,menstrual abnormalities,and infertility.Infrequently,patients will experience androgen-related manifestations of masculinization,such as increased hair,acne,or a low voice.Diagnosis must be confirmed by immunohistochemical analysis of the tissue as clinical symptoms and imaging studies are unreliable.CASE SUMMARY A 14-year-old female presented with amenorrhea.After a thorough medical examination,endocrine and tumor markers analysis,and imaging,a pelvic mass was discovered.The patient also exhibited endocrine dysfunction but was not positive for any tumor markers.The patient underwent surgery to remove the ovarian tumor.Immunohistochemical analysis of the resected specimen indicated an OSST.During the postoperative follow-up,the patient had attained menarche.CONCLUSION This case’s clinical manifestation of endocrine dysfunction due to OSST provides new insights that will assist clinicians in the diagnosis and treatment of this common tumor.
文摘In this paper,we comment on the article by Gu et al published in 2024,invest-igating whether there were differences in the clinical/perioperative outcomes of endoscopic and laparoscopic resections of gastric stromal tumors.Compared with most carcinomas,gastrointestinal stromal tumors are quite common worldwide and have a better prognosis.However,they respond to specific chemotherapies and do not routinely require standard lymphadenectomy.The gastric origin is known to be the most represented.Survival after proven radical surgery is ex-cellent,with recurrences being extremely infrequent.Currently,induction/pe-rioperative chemotherapy for high-risk tumors larger than 5 cm can downstage neoplasia and maintain good survival.Therefore,the standard of care for non-metastatic,resectable tumors is surgical excision(avoiding formal lymphaden-ectomy)with or without chemotherapy.In the case of small-(2 cm)to medium-(5 cm)sized tumors,minimally invasive surgical approaches(laparoscopic or ro-botic)have been advocated,and more recently,a purely endoscopic technique has also been proposed.All these interventions are feasible and effective,although no definitive results have been published to prove the superiority of one over another;however,further investigation of its associated oncologic outcomes is still needed.Unfortunately,rigorous,prospective,randomized controlled trials are challenging to conduct,develop,and receive ethical approval for,whereas the final decision of the surgical route is often related to the availability of instru-mentation and local expertise.
文摘While rare,esophageal gastrointestinal stromal tumors(GISTs)have higher mali-gnant potential and are typically diagnosed at larger sizes compared to gastric GISTs.However,well-defined guidelines for their optimal management remain lacking.Most esophageal GISTs are surgically managed with enucleation,while esophagectomy is reserved for larger tumors.Recent advances in endoscopic techniques,such as endoscopic submucosal dissection and submucosal tunneling endoscopic resection(ER),have allowed for endoscopic removal of submucosal esophageal lesions,including GISTs.Xu et al reported on the clinical and on-cological outcomes of 32 patients with esophageal GISTs treated with ER.The study demonstrated high en bloc resection rates and favorable 5-year overall survival and disease-free survival.However,it primarily focused on small,inci-dentally detected GISTs,with 75%of cases classified as very low or low risk according to the National Institutes of Health criteria.The authors favored the submucosal tunneling ER technique despite its procedural challenges in the upper esophagus.In this editorial,we briefly discuss the advantages and limitations of endoscopic techniques compared to surgical approaches.We also emphasize the need to establish specific management criteria for submucosal esophageal lesions to guide clinical practice.
文摘Heart failure(HF)is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood.Currently,HF remains a leading cause of morbidity and mortality worldwide,imposing a substantial burden on global healthcare systems.Recent advancements have highlighted the therapeutic potential of mesenchymal stromal cells(MSCs)in managing HF.Notably,umbilical cord-derived MSCs(UC-MSCs)have demonstrated superior clinical potential compared to traditional bone marrow-derived MSCs;this is evident in their non-invasive collection process,higher proliferation efficacy,and lower immunogenicity and tumorigenicity,as substantiated by preclinical studies.Although the feasibility and safety of UC-MSCs have been tested in animal models,the application of UC-MSCs in HF treatment remains challenged by issues such as inaccurate targeted migration and low survival rates of UC-MSCs.Therefore,further research and clinical trials are imperative to advance the clinical application of UC-MSCs.
文摘In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.
基金Supported by National Natural Science Foundation of China,No.82002515,No.82273025 and No.82203460China Postdoctoral Science Foundation,No.2022TQ0070 and No.2022M710759Shanghai Municipal Commission of Science and Technology,No.22JC1403003,No.22XD1402200,No.19140901902 and No.22S31903800.
文摘BACKGROUND There are few clinicopathologic characteristics and clinical results for oesophageal gastrointestinal stromal tumours(GISTs).Thus,the objective of this study was to identify the clinicopathologic characteristics and clinical results of oesophageal GISTs.AIM To investigate endoscopic treatment effective of oesophageal GISTs.METHODS It was retrospective research that collected 32 patients with oesophageal GISTs treated by endoscopic resection(ER)between January 2012 and January 2023 in two Hospital.Clinicopathologic,endoscopic records,and follow-up data were collected and analysed.RESULTS Thirty-one patients underwent en bloc resection and 24(75.0%)lesions underwent R0 resection.The size of GISTs was 2.12±1.88 cm.The overall complication rate was 25.0%,including hydrothorax and post-endoscopic submucosal dissection electrocoagulation syndrome.The mean mitotic index was 3.34±5.04(median,1.50;range,1.00-4.00).Eighteen(56.3%),6(18.8%),2(6.3%),and 6(18.8%)patients were identified as very low,low,intermediate,and high risk,respectively.Three patients developed recurrence after a median follow-up of 64.69±33.13 months.The 5-year overall survival rate was 100%,and the disease-free survival rate was 90.6%.CONCLUSION ER is safe and effective for patients with low-risk oesophageal GISTs.Early detection of oesophageal GISTs is essential to achieve a favourable prognosis.
文摘Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative medicine.However,while MSCs have been shown to be safe as a cellular treatment,they have usually been therapeutically ineffective in human diseases.In fact,in many clinical trials it has been shown that MSCs have moderate or poor efficacy.This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs.Recently,specific priming strategies have been used to improve the therapeutic properties of MSCs.In this review,we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs.We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes.Particularly,while hypoxic priming can be used primarily for the treatment of acute diseases,inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders.The shift in approach from regeneration to inflammation implies,in MSCs,a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways.The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.
文摘Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated with neurofibromatosis type 1(NF1),an autosomal dominant genetic disease resulting from pathogenic mutations in the NF1 gene,which encodes the neurofibromin protein.NF1 patients often exhibit multi-system involvement,with café-au-lait macules and neurofibromas being characteristic symptoms.GISTs are a rare complication of NF1,with the tumors most frequently occurring in the small intestine(90%of cases),while occurrences in the stomach are rare.CASE SUMMARY A 51-year-old woman presented to the emergency department with complaints of dizziness,fatigue,chest tightness,and dark stools.Initial examination revealed a red blood cell count of 1.99×1012/L and a hemoglobin level of 43 g/L.She underwent blood transfusions and fluid replacement to stabilize her condition.Further investigations identified typical café-au-lait macules on her trunk,limbs,and face,along with neurofibromas.Endoscopy showed coffee-colored fluid in the gastric cavity,a large submucosal elevation with an exudative covering,and ulcer formation on the gastric fundus.Exploratory laparoscopy confirmed the tumor’s origin in the gastric fundus,and resection of the giant GIST was performed.Pathological analysis revealed a necrotic GIST measuring 18 cm×14 cm,classified as high-risk,with approximately 5 mitotic figures per 10 high-power fields and no tumor at the margins.Immunohistochemistry results were CD117(+),delay of germination 1(+),CD34(+),and succinate dehydrogenase complex iron sulfur subunit B intact expression.Genetic testing using next-generation sequencing confirmed an NF1 gene mutation.The patient underwent successful tumor resection and was discharged home with postoperative regorafenib therapy.A follow-up at one year showed no recurrence.CONCLUSION Given the diversity of clinical symptoms associated with NF1 and the complexity of NF1-related GISTs,surgical resection with complete tumor removal remains the preferred treatment option.However,the absence of a standardized treatment protocol for adjuvant therapy presents numerous challenges for clinicians.
基金National Natural Science Foundation of China:Study on the Molecular Mechanism of the Regulation of Crypt Goblet Cell Pyroptosis and Exocytosis to Repair Ulcerative Colitis Mucus Barrier by the Method of Clearing and Opening the Xuanfu from the Perspective of"Xuanfu-Crypt"(No.82305143),and National Natural Science Foundation of China:Exploring the Molecular Mechanism of"Hewei Jiangni Fang"Intervention in Non-erosive Reflux Disease Esophageal Hypersensitivity from the Perspective of Mas-related Gene X2/Stromal Interaction Molecule 1/Cell Adhesion Molecule 1 Pathway Regulation of Mast Cell/Dorsal Root Ganglion Communication based on the"Xinkai-Kujiang"Method(No.82374401)。
文摘OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.
基金Supported by Taishan Scholar Special Funding,No.tsqnz20240858Medical and Health Technology Project of Shandong Province,No.202402050122+4 种基金Science and Technology Development Plan of Jinan Municipal Health Commission,No.2024301008Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau,No.202430055Natural Science Foundation of Jiangxi Province,No.20224BAB206077Gansu Provincial Hospital Intra-Hospital Research Fund Project,No.22GSSYB-6and the 2022 Master/Doctor/Postdoctoral Program of National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor,No.NHCDP2022004 and No.NHCDP2022008.
文摘Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.
基金Supported by the Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
文摘Decisions regarding the management of patients with esophageal gastrointestinal tumors(EGISTs)are very challenging,as there are still no clear guidelines on the treatment of these tumors due to their rarity.Surgery remains the standard treatment,but it is known that surgical procedures performed on the esophagus are related to a high risk of serious postoperative complications and impaired quality of life.Endoscopic resection is both safe and effective for patients with low-risk EGISTs.This article presents the current therapeutic options in patients with EGISTs,including both the endoscopic and surgical approach,and discusses the results,strengths and limitations of the recent article by Xu et al regarding the endoscopic treatment outcome of EGISTs.
文摘Zhao et al’s investigation on the assessment of inflammatory markers prognostic value for relapse-free survival in patients with gastrointestinal stromal tumor(GIST)using a nomogram-based approach is a scientific approach.This study explored the potential of an inflammatory marker-based nomograph model,highlighting the relapse-free survival-associated risk factors prognostic potential in patients with GIST.The author assessed 124 samples from patients with GIST to find an association between inflammatory markers and tumor size in a retrospective study using multivariate regression analysis.Further,a nomogram model was developed to identify the independent risk factors for the prognosis.GIST clinical treatment can use preoperative monocyte/lymphocyte ratio and platelet/lymphocyte ratio for relapse-free survival prognosis as independent factors.
