Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess ca...Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.展开更多
Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus...Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.展开更多
The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human ...The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.展开更多
BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneum...BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.展开更多
In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cell...In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem Cells.Despite over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be addressed.The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs.As we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.展开更多
Transoral endoscopic resections in treating upper gastrointestinal submucosal lesions have the advantages of maintaining the integrity of the gastrointestinal lumen,avoiding perforation and reducing gastrointestinal f...Transoral endoscopic resections in treating upper gastrointestinal submucosal lesions have the advantages of maintaining the integrity of the gastrointestinal lumen,avoiding perforation and reducing gastrointestinal fistulae.They are becoming more widely used in clinical practice,but,they may also present a variety of complications.Gas-related complications are one of the most common,which can be left untreated if the symptoms are mild,but in severe cases,they can lead to rapid changes in the respiratory and circulatory systems in a short period,which can be life-threatening.Therefore,it is important to predict the occurrence of gas-related complications early and take preventive measures actively.Based on the authors'results in the prepublication of the article“Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions,”and in conjunction with our evaluation and additions to the relevant content,radiographs may help screen patients at high risk for gas-related complications.Controlling blood glucose levels,shortening the duration of surgery,and choosing the most appropriate surgical resection may positively impact the prognosis of patients at high risk for gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions.展开更多
PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory dise...PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.展开更多
Adipose mesenchymal stem cells(ADSCs)have protective effects against glutamate-induced excitotoxicity,but ADSCs are limited in use for treatment of optic nerve injury.Studies have shown that the extracellular vesicles...Adipose mesenchymal stem cells(ADSCs)have protective effects against glutamate-induced excitotoxicity,but ADSCs are limited in use for treatment of optic nerve injury.Studies have shown that the extracellular vesicles(EVs)secreted by ADSCs(ADSC-EVs)not only have the function of ADSCs,but also have unique advantages including non-immunogenicity,low probability of abnormal growth,and easy access to target cells.In the present study,we showed that intravitreal injection of ADSC-EVs substantially reduced glutamate-induced damage to retinal morphology and electroretinography.In addition,R28 cell pretreatment with ADSC-EVs before injury inhibited glutamate-induced overload of intracellular calcium,downregulation ofα-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor(AMPAR)subunit GluA2,and phosphorylation of GluA2 and protein kinase C alpha in vitro.A protein kinase C alpha agonist,12-O-tetradecanoylphorbol 13-acetate,inhibited the neuroprotective effects of ADSC-EVs on glutamate-induced R28 cells.These findings suggest that ADSCEVs ameliorate glutamate-induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation.展开更多
Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or cont...Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.展开更多
Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the u...Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.展开更多
Background: Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective stu...Background: Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective study was to evaluate the efficacy and safety of EUS-FNB in patients with gallbladder masses. Methods: The study samples were composed of patients from March 2015 to July 2019 who needed to identify the nature of gallbladder masses through EUS-FNB. The outcomes of this study were the adequacy of specimens, diagnostic yields, technical feasibility, and adverse events of the EUS-FNB in gallbladder masses. Results: A total of 27 consecutive patients with a median age of 58 years were included in this study. The 22-gauge FNB needle was feasible in all lesions. The median follow-up period of the patients was 294 days. The specimens sufficient for diagnosis account for 89%(24/27) and 93%(25/27) in cytology and histology, respectively. The overall diagnostic yields for malignancy showed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.45% [95% confidence interval(CI): 75.12%-99.76%], 100%(95% CI: 46.29%-10 0%), 10 0%(95% CI: 80.76%-100%), 83.33%(95% CI: 36.48%-99.12%), and 96.30%(95% CI: 80.20%-99.99%), respectively. The subgroup analysis revealed that FNB could obtain sufficient specimens and high diagnostic yields in both gallbladder mass < 20.5 mm group and ≥20.5 mm group. One patient experienced mild abdominal pain after the procedure and recovered within one day. Conclusions: EUS-FNB is a reasonable diagnostic tool for the pretreatment diagnosis of patients with gallbladder masses, especially for patients who may miss the opportunity of surgery and need sufficient specimens to identify the pathological type so as to determine chemotherapy regimens. Further largescale studies are needed to confirm our conclusion.展开更多
Background:Pulmonary arterial hypertension(PAH)is a chronic and progressive disease that is strongly associated with dysregulation of glucose metabolism.Alterations in nuclear receptor subfamily 4 group A member 1(NR4...Background:Pulmonary arterial hypertension(PAH)is a chronic and progressive disease that is strongly associated with dysregulation of glucose metabolism.Alterations in nuclear receptor subfamily 4 group A member 1(NR4A1)activity alter the outcome of PAH.This study aimed to investigate the effects of NR4A1 on glycolysis in PAH and its underlying mechanisms.Methods:This study included twenty healthy volunteers and twenty-three PAH patients,and plasma samples were collected from the participants.To mimic the conditions of PAH in vitro,a hypoxia-induced model of pulmonary artery smooth muscle cell(PASMC)model was established.The proliferation of PASMCs was assessed using CCK8 assays.Results:Levels of NR4A1,hypoxia-inducible factor-1α(HIF-1α),and various glycolysis-related enzymes were measured.In addition,extracellular glucose and lactate production were assessed.The interaction between NR4A1 and HIF-1αwas evaluated by co-immunoprecipitation assays.Levels of NR4A1 and HIF-1αwas increased in PAH patients,and exposure to hypoxia resulted in increased levels of NR4A1 and HIF-1αin PASMCs.NR4A1 interacted with HIF-1α.NR4A1 overexpression enhanced hypoxia-induced expression of HIF-1α,GLUT1,PKM2,HK2,and CD36,decreased glucose levels,increased lactate levels and promoted hypoxic PASMC viability.Conversely,silencing NR4A1 decreased hypoxia-induced expression of HIF-1α,GLUT1,PKM2,HK2,and CD36,promoted glucose production,reduced lactate levels and inhibited hypoxic PASMC viability.Furthermore,overexpression of HIF-1αreversed the regulation of glycolysis caused by NR4A1 knockdown.Conclusion:NR4A1 enhances glycolysis in hypoxia-induced PASMCs by upregulating HIF-1α.Our findings indicate that the management of NR4A1 activity may be a promising strategy for PAH therapy.展开更多
BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided p...BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.展开更多
In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made breakthroughs in the treatment of hematological tumors. However, due to the different characteristics of solid tumors from hematological tumor...In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made breakthroughs in the treatment of hematological tumors. However, due to the different characteristics of solid tumors from hematological tumors, CAR-T has not achieved good efficacy in the treatment of solid tumors. The key factors limiting the efficacy of CAR-T mainly include the solid tumor cells themselves and their special tumor microenvironment (TME), which damage CAR-T function in multiple processes such as CAR-T infiltration to tumor tissue sites, CAR-T maintaining anti-tumor activity in TME, and target recognition and killing of tumor cells by CAR-T. To solve these problems, more and more preclinical studies have proposed potentially effective solutions, and corresponding clinical studies have been carried out one after another. In this article, the existing challenges and corresponding optimization strategies of CAR-T cell therapy for solid tumors will be reviewed, to provide a reference for the future exploration of CAR-T therapy.展开更多
BACKGROUND Recently,a group of hepatologists proposed to rename non-alcoholic fatty liver disease(NAFLD)as metabolic associated fatty liver disease(MAFLD)with modified diagnostic criteria.It is important to note,howev...BACKGROUND Recently,a group of hepatologists proposed to rename non-alcoholic fatty liver disease(NAFLD)as metabolic associated fatty liver disease(MAFLD)with modified diagnostic criteria.It is important to note,however,that there are some differences between the diagnostic criteria used for NAFLD and MAFLD.Since the research on MAFLD is just beginning,however,evidence on its incidence and prevalence in the general population and in specic subpopulations remains limited.AIM To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD.Exploring risk factors of MAFLD individuals.METHODS This was a retrospective,cross-sectional study.A total of 85242 adults were selected from the Chinese health management database in 2017–2022.The data of general information,laboratory indicators,lifestyle management and psychological status were obtained.MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions:Overweight/obesity,type 2 diabetes mellitus(T2DM)or metabolic dysregulation.Metabolic factors were not considered in NAFLD diagnosis standard.The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics.Continuous variables normally distributed were expressed as means±SD.Categorical variables were expressed as frequencies and proportions.Binary logistic regression was used to determine risk factors of the MAFLD.RESULTS The prevalence of MAFLD and NAFLD was 40.5%and 31.0%,respectively.The MAFLD or NAFLD population is more likely to be older(M:47.19±10.82 vs 43.43±11.96;N:47.72±11.17 vs 43.71±11.66),male(M:77.21%vs 44.43%;N:67.90%vs 53.12%)and high body mass index(M:26.79±2.69 vs 22.44±2.48;N:26.29±2.84 vs 23.29±3.12)than the non-MAFLD or non-MAFLD population.In multivariate analysis,general information(e.g.,≥2 metabolic abnormalities OR=3.38,(95%CI:2.99-3.81),P<0.001;diastolic blood pressure OR=1.01,(95%CI:1.00–1.01),P=0.002),laboratory results[e.g.,total bilirubin(TBIL)OR=0.98,(95%CI:0.98-0.99),P<0.001;serum uric acid(SUA)OR=1.01,(95%CI:1.01-1.01),P<0.001],and lifestyle factors[e.g.,drink beverage OR=0.32,(95%CI:0.17-0.63),P=0.001]were influence factors for MAFLD.Our study results offer new insight into potential risk factors associated with fatty liver disease,including SUA,TBIL and creatinine,all of which are related to chronic renal disease(CKD).CONCLUSION MAFLD is more prevalent than NAFLD,with two-fifths of individuals meeting the diagnosis criteria.MAFLD and NAFLD populations have different clinical characteristics.CKD may be related with MAFLD.展开更多
The incidence of cholecystitis is relatively high in developed countries and may usually be attributed to gallstones,the treatment for which involves complete surgical removal of the gallbladder(cholecystectomy).Bile ...The incidence of cholecystitis is relatively high in developed countries and may usually be attributed to gallstones,the treatment for which involves complete surgical removal of the gallbladder(cholecystectomy).Bile acids produced following cholecystectomy continue to flow into the duodenum but are poorly absorbed by the colon.Excessive bile acids in the colon stimulate mucosal secretion of water and electrolytes leading,in severe cases,to diarrhoea.Bile acid diarrhoea(BAD)is difficult to diagnose,requiring a comprehensive medical history and physical examination in combination with laboratory evaluation.The current work reviews the diagnosis and treatment of BAD following chole-cystectomy.展开更多
Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neurop...Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neuropsychiatric systemic lupus erythematosus.Two recipients developed Scedosporiosis after kidney transplantation from the same donor.Recipient 1 died of central nervous system infection due to S.boydii based on the clinical presentations,and the positive metagenomic next-generation sequencing(mNGS)and culture results for the cerebrospinal fluid.The other recipient with urinary tract obstruction due to S.boydii,which was identified through the positive culture and mNGS results of the removed stents,was successfully treated by stent replacement and voriconazole administration.Undiagnosed disseminated donor infection and the transmission of S.boydii should be given attention,particularly when the donor and recipients have primary immunodeficiency disease.The screening of donors and recipients for S.boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients,due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.展开更多
The fundamental importance of sex lies in the need for reproduction and species continuity. For humans, sexual expression is an important source of physical pleasure and emotional intimacy. Healthy sexual expression i...The fundamental importance of sex lies in the need for reproduction and species continuity. For humans, sexual expression is an important source of physical pleasure and emotional intimacy. Healthy sexual expression is closely related to well-being, health and overall quality of life in both men and women. Sexual activity is also considered an important determinant of quality of life. At present, questions about sex are still largely ignored in routine consultations in almost all medical specialties. The factors affecting sexual activity are complex and can be divided into the influence of bio-psycho-sociological factors. Biological influences include anthropometric parameters, sexual function, lifestyle, neuroendocrine system, and diseases;psychological influences include psychological status, mental illness, and sexual attitudes;sociological influences include factors such as marriage, occupation, and economic status. With the epidemic and outbreak of Coronavirus disease 2019 (COVID-19), people’s way of life and work has changed, which also has a great impact on sexual activities. This article will provide a systematic review of factors related to male sexual activity.展开更多
Biocompatible devices are widely employed in modernized lives and medical fields in the forms of wearable and implantable devices,raising higher requirements on the battery biocompatibility,high safety,low cost,and ex...Biocompatible devices are widely employed in modernized lives and medical fields in the forms of wearable and implantable devices,raising higher requirements on the battery biocompatibility,high safety,low cost,and excellent electrochemical performance,which become the evaluation criteria toward developing feasible biocompatible batteries.Herein,through conducting the battery implantation tests and leakage scene simulations on New Zealand rabbits,zinc sulfate electrolyte is proved to exhibit higher biosecurity and turns out to be one of the ideal zinc salts for biocompatible zinc-ion batteries(ZIBs).Furthermore,in order to mitigate the notorious dendrite growth and hydrogen evolution in mildly acidic electrolyte as well as improve their operating stability,Sn hetero nucleus is introduced to stabilize the zinc anode,which not only facilitates the planar zinc deposition,but also contributes to higher hydrogen evolution overpotential.Finally,a long lifetime of 1500 h for the symmetrical cell,the specific capacity of 150 mAh g^(-1)under 0.5 A g^(-1)for the Zn-MnO_(2)battery and 212 mAh g^(-1)under 5 A g^(-1)for the Zn—NH4V4O10 battery are obtained.This work may provide unique perspectives on biocompatible ZIBs toward the biosecurity of their cell components.展开更多
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
基金supported by grants from the National Natural Science Foundation of China(No.81971891,No.82172196 and No.82372507)the Natural Science Foundation of Hunan Province(No.2023JJ40804)the Key Laboratory of Emergency and Trauma of Ministry of Education(Hainan Medical University,No.KLET-202210).
文摘Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.
基金supported by the Hunan Provincial Science and Technology Department Project(2015WK3012)the National Natural Science Foundation of China(No.81571021)+3 种基金R&D of Key Project of Hunan Provincial Science and Technology Department(2022SK2010)R&D of Key Technology of Light Metal Air Battery,Transformation and Industrialization of Scientific and Technological Achievements of Hunan Province(2020GK2071)R&D of Key Technology and Materials of Magnesium Air Battery,Transformation of Scientific and Technological Achievements of Changsha City(Kh2005186)Technology Fundation(2021JCJQ-JJ-0432)。
文摘The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.
基金approved by the Ethics Committee of the Third Xiangya Hospital in accordance with the Declaration of Helsinki(No.24029).
文摘BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.
基金National Natural Science Foundation of China,No.82172196,No.82372507,and No.81971891.
文摘In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem Cells.Despite over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be addressed.The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs.As we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.
文摘Transoral endoscopic resections in treating upper gastrointestinal submucosal lesions have the advantages of maintaining the integrity of the gastrointestinal lumen,avoiding perforation and reducing gastrointestinal fistulae.They are becoming more widely used in clinical practice,but,they may also present a variety of complications.Gas-related complications are one of the most common,which can be left untreated if the symptoms are mild,but in severe cases,they can lead to rapid changes in the respiratory and circulatory systems in a short period,which can be life-threatening.Therefore,it is important to predict the occurrence of gas-related complications early and take preventive measures actively.Based on the authors'results in the prepublication of the article“Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions,”and in conjunction with our evaluation and additions to the relevant content,radiographs may help screen patients at high risk for gas-related complications.Controlling blood glucose levels,shortening the duration of surgery,and choosing the most appropriate surgical resection may positively impact the prognosis of patients at high risk for gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions.
基金supported by the National Natural Science Foundation of China,Nos.81772134,81971891,82172196,81571939(ail to KX)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of Ministry of Education,No.KLET-202108(to KX)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University of China,No.2020zzts218(to WTY)Hunan Provincial Innovation Foundation for Postgraduate of China,No.CX20200116(to WTY)。
文摘PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.
基金supported by the National Key R&D Program of China,No.2016YFC1201800(to JFH)the Key Research and Development Program of Hunan Province,Nos.2018SK2090(to JFH),2022SK2079(to JFH)+2 种基金the Natural Science Foundation of Hu nan Province,No.2021JJ30891(to DC)the Human Resource Bank Program of Hunan Province,No.2020TP3003(to JFH)the School-Enterprise Joint Program of Central South University,No.2021XQLH092(to TQD)。
文摘Adipose mesenchymal stem cells(ADSCs)have protective effects against glutamate-induced excitotoxicity,but ADSCs are limited in use for treatment of optic nerve injury.Studies have shown that the extracellular vesicles(EVs)secreted by ADSCs(ADSC-EVs)not only have the function of ADSCs,but also have unique advantages including non-immunogenicity,low probability of abnormal growth,and easy access to target cells.In the present study,we showed that intravitreal injection of ADSC-EVs substantially reduced glutamate-induced damage to retinal morphology and electroretinography.In addition,R28 cell pretreatment with ADSC-EVs before injury inhibited glutamate-induced overload of intracellular calcium,downregulation ofα-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor(AMPAR)subunit GluA2,and phosphorylation of GluA2 and protein kinase C alpha in vitro.A protein kinase C alpha agonist,12-O-tetradecanoylphorbol 13-acetate,inhibited the neuroprotective effects of ADSC-EVs on glutamate-induced R28 cells.These findings suggest that ADSCEVs ameliorate glutamate-induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation.
基金Supported by the National Natural Science Foundation of China,No.81971891 and No.82172196Key Laboratory of Emergency and Trauma(Hainan Medical University)of Ministry of Education,No.KLET-202108the College Students’Innovation and Entrepreneurship Project,No.S20210026020013.
文摘Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.
文摘Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.
基金supported by a grant from the National Ma-jor Diseases Multidisciplinary Cooperative Diagnosis and Treat-ment Project-Gastrointestinal Cancer MDT Diagnosis and Treat-ment Project
文摘Background: Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective study was to evaluate the efficacy and safety of EUS-FNB in patients with gallbladder masses. Methods: The study samples were composed of patients from March 2015 to July 2019 who needed to identify the nature of gallbladder masses through EUS-FNB. The outcomes of this study were the adequacy of specimens, diagnostic yields, technical feasibility, and adverse events of the EUS-FNB in gallbladder masses. Results: A total of 27 consecutive patients with a median age of 58 years were included in this study. The 22-gauge FNB needle was feasible in all lesions. The median follow-up period of the patients was 294 days. The specimens sufficient for diagnosis account for 89%(24/27) and 93%(25/27) in cytology and histology, respectively. The overall diagnostic yields for malignancy showed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.45% [95% confidence interval(CI): 75.12%-99.76%], 100%(95% CI: 46.29%-10 0%), 10 0%(95% CI: 80.76%-100%), 83.33%(95% CI: 36.48%-99.12%), and 96.30%(95% CI: 80.20%-99.99%), respectively. The subgroup analysis revealed that FNB could obtain sufficient specimens and high diagnostic yields in both gallbladder mass < 20.5 mm group and ≥20.5 mm group. One patient experienced mild abdominal pain after the procedure and recovered within one day. Conclusions: EUS-FNB is a reasonable diagnostic tool for the pretreatment diagnosis of patients with gallbladder masses, especially for patients who may miss the opportunity of surgery and need sufficient specimens to identify the pathological type so as to determine chemotherapy regimens. Further largescale studies are needed to confirm our conclusion.
基金supported by the National Natural Science Foundation of China(No.82000300).
文摘Background:Pulmonary arterial hypertension(PAH)is a chronic and progressive disease that is strongly associated with dysregulation of glucose metabolism.Alterations in nuclear receptor subfamily 4 group A member 1(NR4A1)activity alter the outcome of PAH.This study aimed to investigate the effects of NR4A1 on glycolysis in PAH and its underlying mechanisms.Methods:This study included twenty healthy volunteers and twenty-three PAH patients,and plasma samples were collected from the participants.To mimic the conditions of PAH in vitro,a hypoxia-induced model of pulmonary artery smooth muscle cell(PASMC)model was established.The proliferation of PASMCs was assessed using CCK8 assays.Results:Levels of NR4A1,hypoxia-inducible factor-1α(HIF-1α),and various glycolysis-related enzymes were measured.In addition,extracellular glucose and lactate production were assessed.The interaction between NR4A1 and HIF-1αwas evaluated by co-immunoprecipitation assays.Levels of NR4A1 and HIF-1αwas increased in PAH patients,and exposure to hypoxia resulted in increased levels of NR4A1 and HIF-1αin PASMCs.NR4A1 interacted with HIF-1α.NR4A1 overexpression enhanced hypoxia-induced expression of HIF-1α,GLUT1,PKM2,HK2,and CD36,decreased glucose levels,increased lactate levels and promoted hypoxic PASMC viability.Conversely,silencing NR4A1 decreased hypoxia-induced expression of HIF-1α,GLUT1,PKM2,HK2,and CD36,promoted glucose production,reduced lactate levels and inhibited hypoxic PASMC viability.Furthermore,overexpression of HIF-1αreversed the regulation of glycolysis caused by NR4A1 knockdown.Conclusion:NR4A1 enhances glycolysis in hypoxia-induced PASMCs by upregulating HIF-1α.Our findings indicate that the management of NR4A1 activity may be a promising strategy for PAH therapy.
基金Supported by the National Natural Science Foundation of China,No. 82270594National Natural Science Foundation for Youths of China,No. 882002614 and No. 82103151+4 种基金Hunan Provincial Natural Science Foundation of China,No. 2020JJ4853Scientific Research Project of Hunan Provincial Health Commission,No. 202103032097Outstanding Youth Foundation of Hunan Province,No. 2022JJ20092Hunan Provincial Natural Science Foundation of China for Youths,No. 2021JJ40935 and No. 2020JJ5609Wisdom Accumulation and Talent Cultivation Project of Third Xiangya Hospital of Central South University,No. YX202103
文摘BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.
文摘In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has made breakthroughs in the treatment of hematological tumors. However, due to the different characteristics of solid tumors from hematological tumors, CAR-T has not achieved good efficacy in the treatment of solid tumors. The key factors limiting the efficacy of CAR-T mainly include the solid tumor cells themselves and their special tumor microenvironment (TME), which damage CAR-T function in multiple processes such as CAR-T infiltration to tumor tissue sites, CAR-T maintaining anti-tumor activity in TME, and target recognition and killing of tumor cells by CAR-T. To solve these problems, more and more preclinical studies have proposed potentially effective solutions, and corresponding clinical studies have been carried out one after another. In this article, the existing challenges and corresponding optimization strategies of CAR-T cell therapy for solid tumors will be reviewed, to provide a reference for the future exploration of CAR-T therapy.
基金Supported by National Natural Science Foundation of China,No.72074225Hunan Provincial Key R&D Program,China,No.2021SK2024.
文摘BACKGROUND Recently,a group of hepatologists proposed to rename non-alcoholic fatty liver disease(NAFLD)as metabolic associated fatty liver disease(MAFLD)with modified diagnostic criteria.It is important to note,however,that there are some differences between the diagnostic criteria used for NAFLD and MAFLD.Since the research on MAFLD is just beginning,however,evidence on its incidence and prevalence in the general population and in specic subpopulations remains limited.AIM To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD.Exploring risk factors of MAFLD individuals.METHODS This was a retrospective,cross-sectional study.A total of 85242 adults were selected from the Chinese health management database in 2017–2022.The data of general information,laboratory indicators,lifestyle management and psychological status were obtained.MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions:Overweight/obesity,type 2 diabetes mellitus(T2DM)or metabolic dysregulation.Metabolic factors were not considered in NAFLD diagnosis standard.The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics.Continuous variables normally distributed were expressed as means±SD.Categorical variables were expressed as frequencies and proportions.Binary logistic regression was used to determine risk factors of the MAFLD.RESULTS The prevalence of MAFLD and NAFLD was 40.5%and 31.0%,respectively.The MAFLD or NAFLD population is more likely to be older(M:47.19±10.82 vs 43.43±11.96;N:47.72±11.17 vs 43.71±11.66),male(M:77.21%vs 44.43%;N:67.90%vs 53.12%)and high body mass index(M:26.79±2.69 vs 22.44±2.48;N:26.29±2.84 vs 23.29±3.12)than the non-MAFLD or non-MAFLD population.In multivariate analysis,general information(e.g.,≥2 metabolic abnormalities OR=3.38,(95%CI:2.99-3.81),P<0.001;diastolic blood pressure OR=1.01,(95%CI:1.00–1.01),P=0.002),laboratory results[e.g.,total bilirubin(TBIL)OR=0.98,(95%CI:0.98-0.99),P<0.001;serum uric acid(SUA)OR=1.01,(95%CI:1.01-1.01),P<0.001],and lifestyle factors[e.g.,drink beverage OR=0.32,(95%CI:0.17-0.63),P=0.001]were influence factors for MAFLD.Our study results offer new insight into potential risk factors associated with fatty liver disease,including SUA,TBIL and creatinine,all of which are related to chronic renal disease(CKD).CONCLUSION MAFLD is more prevalent than NAFLD,with two-fifths of individuals meeting the diagnosis criteria.MAFLD and NAFLD populations have different clinical characteristics.CKD may be related with MAFLD.
文摘The incidence of cholecystitis is relatively high in developed countries and may usually be attributed to gallstones,the treatment for which involves complete surgical removal of the gallbladder(cholecystectomy).Bile acids produced following cholecystectomy continue to flow into the duodenum but are poorly absorbed by the colon.Excessive bile acids in the colon stimulate mucosal secretion of water and electrolytes leading,in severe cases,to diarrhoea.Bile acid diarrhoea(BAD)is difficult to diagnose,requiring a comprehensive medical history and physical examination in combination with laboratory evaluation.The current work reviews the diagnosis and treatment of BAD following chole-cystectomy.
基金supported by National Key Clinical Specialty Construction Project(General Surgery).
文摘Donor-derived infection(DDI)associated with Scedosporium spp is extremely rare,and results in a very poor prognosis.The present study reports a probable DDI due to Scedosporium boydii(S.boydii)from a donor with neuropsychiatric systemic lupus erythematosus.Two recipients developed Scedosporiosis after kidney transplantation from the same donor.Recipient 1 died of central nervous system infection due to S.boydii based on the clinical presentations,and the positive metagenomic next-generation sequencing(mNGS)and culture results for the cerebrospinal fluid.The other recipient with urinary tract obstruction due to S.boydii,which was identified through the positive culture and mNGS results of the removed stents,was successfully treated by stent replacement and voriconazole administration.Undiagnosed disseminated donor infection and the transmission of S.boydii should be given attention,particularly when the donor and recipients have primary immunodeficiency disease.The screening of donors and recipients for S.boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients,due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.
文摘The fundamental importance of sex lies in the need for reproduction and species continuity. For humans, sexual expression is an important source of physical pleasure and emotional intimacy. Healthy sexual expression is closely related to well-being, health and overall quality of life in both men and women. Sexual activity is also considered an important determinant of quality of life. At present, questions about sex are still largely ignored in routine consultations in almost all medical specialties. The factors affecting sexual activity are complex and can be divided into the influence of bio-psycho-sociological factors. Biological influences include anthropometric parameters, sexual function, lifestyle, neuroendocrine system, and diseases;psychological influences include psychological status, mental illness, and sexual attitudes;sociological influences include factors such as marriage, occupation, and economic status. With the epidemic and outbreak of Coronavirus disease 2019 (COVID-19), people’s way of life and work has changed, which also has a great impact on sexual activities. This article will provide a systematic review of factors related to male sexual activity.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.82103472,82202480,and 52372252)the Hunan Natural Science Fund for Distinguished Young Scholar(2021JJ10064)the Program of Youth Talent Support for Hunan Province(2020RC3011).
文摘Biocompatible devices are widely employed in modernized lives and medical fields in the forms of wearable and implantable devices,raising higher requirements on the battery biocompatibility,high safety,low cost,and excellent electrochemical performance,which become the evaluation criteria toward developing feasible biocompatible batteries.Herein,through conducting the battery implantation tests and leakage scene simulations on New Zealand rabbits,zinc sulfate electrolyte is proved to exhibit higher biosecurity and turns out to be one of the ideal zinc salts for biocompatible zinc-ion batteries(ZIBs).Furthermore,in order to mitigate the notorious dendrite growth and hydrogen evolution in mildly acidic electrolyte as well as improve their operating stability,Sn hetero nucleus is introduced to stabilize the zinc anode,which not only facilitates the planar zinc deposition,but also contributes to higher hydrogen evolution overpotential.Finally,a long lifetime of 1500 h for the symmetrical cell,the specific capacity of 150 mAh g^(-1)under 0.5 A g^(-1)for the Zn-MnO_(2)battery and 212 mAh g^(-1)under 5 A g^(-1)for the Zn—NH4V4O10 battery are obtained.This work may provide unique perspectives on biocompatible ZIBs toward the biosecurity of their cell components.
