BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is a procedure used for patients with initially unresectable colorectal liver metastases(CRLM).However,the procedure has bee...BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is a procedure used for patients with initially unresectable colorectal liver metastases(CRLM).However,the procedure has been reported to be associated with high morbidity and mortality.Laparoscopic ALPPS has recently been reported as a minimally invasive technique that reduces perioperative risks.AIM To assess the safety and feasibility of full laparoscopic ALPPS in patients with CRLM.METHODS A retrospective analysis was conducted on all consecutive patients with CRLM who underwent full laparoscopic ALPPS at the Sixth Affiliated Hospital of Sun Yat-sen University between March 2021 and July 2024.RESULTS Fifteen patients were included,13 with synchronous liver metastases.Nine patients had more than five liver tumors,with the highest count being 22.The median diameter of the largest lesion was 2.8 cm on preoperative imaging.No extrahepatic metastases were observed.RAS mutations were detected in nine patients,and 14 underwent preoperative chemotherapy.The median increase in future liver remnant volume during the interstage interval was 47.0%.All patients underwent R0 resection.Overall complication rates were 13.3%(stage 1)and 53.3%(stage 2),while major complication rates(Clavien-Dindo≥IIIa)were 13.3%(stage 1)and 33.3%(stage 2).No mortality occurred in either stage.The median hospital stay after stage 2 was 10 days.CONCLUSION Full laparoscopic ALPPS for CRLM is safe and feasible,with the potential for reduced morbidity and mortality,offering radical resection opportunities for patients with initially unresectable CRLM.展开更多
The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory ...The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
The field of biomedical imaging has been revolutionized by deep learning techniques.This special issue is focused on the theme of“AI-based Image Analysis”.Because there are so many conferences and journals in this f...The field of biomedical imaging has been revolutionized by deep learning techniques.This special issue is focused on the theme of“AI-based Image Analysis”.Because there are so many conferences and journals in this field,our special issue can only be a small snapshot of a much bigger and highly dynamic picture.In this special issue,we present six papers that highlight the power of deep learning in solving challenging biomedical imaging and image analysis problems.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide.Sorafenib is still a recommended treatment for a large proportion of patients...BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide.Sorafenib is still a recommended treatment for a large proportion of patients with advanced HCC.Different patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 cells.AIM To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 cells.Various available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 cells.METHODS HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 hours.Total RNA,including small and long RNA,was extracted with a commercial miRNeasy kit.RNAseq was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory axes.RESULTS MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 cells.SNHG12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 cells.The axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib treatment.CONCLUSION Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.展开更多
Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event cau...Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).展开更多
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA scree...AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.展开更多
Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM...Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.展开更多
Background : Scleral fixation of intraocular lenses is a surgical technique that involves anchoring an artificial lens to the sclera. Traditional approaches, such as capsular bag placement, may not be feasible in cert...Background : Scleral fixation of intraocular lenses is a surgical technique that involves anchoring an artificial lens to the sclera. Traditional approaches, such as capsular bag placement, may not be feasible in certain situations, making scleral fixation a valuable alternative. The scleral reactions to different types of suture materials are not fully understood. Therefore, the present study describes the microscopic structure of normal scleral tissue and its changes with suture materials. Methods : We compared six groups of rabbit eyes focusing on the sclera: group with polytetrafluoroethylene( PTFE) chain, PTFE fiber, polypropylene( PPE) fiber and control groups. multilevel sampling and stereological methods were used for histological quantification of the leukocyte infiltration fractions and type Ⅰ and type Ⅲ collagen. Results : Quantitative histological evaluation revealed the following:(1) For all materials used, inflammation was present in the surrounding scleral tissue compared with healthy controls. However, leukocyte infiltration in the sclera was not statistically different between the materials.(2) As part of the evaluation of collagen, the greatest changes occurred in the PTFE fiber group at 2 weeks postoperatively. In the PTFE chain group, more significant changes were visible at 4 weeks.(3) The changes in the PPE fiber group compared to healthy scleral tissue were the least significant. Conclusions : From a histological point of view, it is evident that there are differences in the quantitative parameters between the untouched sclera and the sclera with suture material. Furthermore, distinctions were observed among various materials and across different time intervals.展开更多
BACKGROUND Rectal neuroendocrine tumors(NETs)smaller than 10 mm and well-differentiated tumors are generally considered to have a low risk of lymph node and distant metastasis,making them suitable for endoscopic resec...BACKGROUND Rectal neuroendocrine tumors(NETs)smaller than 10 mm and well-differentiated tumors are generally considered to have a low risk of lymph node and distant metastasis,making them suitable for endoscopic resection.In contrast,tumors≥20 mm in size typically require surgical resection.However,the optimal management of intermediate-sized(10-15 mm)rectal NETs remains controversial.AIM To compare the clinical outcomes of endoscopic resection of rectal NETs<1 cm and those 1-1.5 cm in size.METHODS A retrospective study was conducted on 1056 patients with rectal NETs treated at the Samsung Medical Center between January 2005 and June 2021.After propensity score matching(1:10)for age,sex,and type of endoscopic resection,225 patients with tumors<1 cm in size and 27 patients with tumors 1-1.5 cm in size were analyzed.RESULTS Surgical resection was more frequent in the 1-1.5 cm group(37.2%)than in the<1 cm group(10.7%)(P<0.01).Endoscopic submucosal dissection was also more commonly performed in the 1-1.5 cm group(48.1%vs 18.5%,P<0.01).Negative resection margins were achieved in 97.2%of the patients,with no significant difference between the groups(P=0.22).No lymphovascular invasion was observed.During a median follow-up of 54 months,no recurrence occurred in the 1-1.5 cm group,while one case of metachronous recurrence was noted in the<1 cm group(P=1.00).There was no significant difference in recurrence-free survival(P=0.48).CONCLUSION Endoscopic resection of 1-1.5 cm grade 1 rectal NETs yielded comparable outcomes to those<1 cm in size,suggesting its feasibility as a treatment.展开更多
BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are increasingly being used to treat type 2 diabetes mellitus(T2DM)and obesity.Although GLP-1RAs delay gastric emptying,their impact on gastric mucosal vis...BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are increasingly being used to treat type 2 diabetes mellitus(T2DM)and obesity.Although GLP-1RAs delay gastric emptying,their impact on gastric mucosal visibility during upper endoscopy remains uncertain,especially in Asian patients.AIM To investigate the association between GLP-1RA treatment and gastric mucosal visibility during upper endoscopy in Asian patients with T2DM.METHODS The study population included Korean patients who underwent esophagogastroduodenoscopy(EGD)with concomitant GLP-1RA or dipeptidyl peptidase 4 inhibitor(DPP4i)for the treatment of T2DM.A 1:2 propensity score matching between GLP-1RA and DPP4i users resulted in 198 matched patients and 295 matched patients in each group,respectively.Gastric mucosal visibility was assessed by reviewing endoscopy images with a validated scale(POLPREP).In addition,the rates of aborted and repeat EGD and pulmonary aspiration were also assessed.RESULTS Of the 493 matched patients,mean body mass index was 26.0 kg/m^(2).The rate of inadequate gastric mucosal visibility(gastric POLPREP score 0 or 1)was significantly higher in GLP-1RA group than matched DPP4i group(8.6%vs 1.4%,P=0.0007).The rates of aborted EGD and repeat EGD were also significantly higher in GLP-1RA than DPP4i group(7.6%vs 0.7%in both aborted and repeat EGD,P=0.0011).Multivariable logistic regression revealed GLP-1RA use as an independent risk factor for both inadequate gastric mucosal visibility(odds ratio=6.143,95%confidence interval:2.289,20.318,P=0.0008)and aborted EGD(odds ratio=11.099,95%confidence interval:3.172,63.760,P=0.0010).Despite gastric residue,no pulmonary aspiration was reported in either group.CONCLUSION GLP-1RA use was associated with a higher risk of inadequate gastric mucosal visibility and aborted and repeat procedures during upper gastrointestinal endoscopy in Korean patients with T2DM while pulmonary aspiration was not observed.展开更多
The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic aci...The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid(5-ALA).Furthermore,this study aimed to explore the underlying mechanism of the protective effects of 5-ALA.First,we collected and stored mouse testicular fragments in different media,including Hank’s balanced salt solution(HBSS;n=5),Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F12;n=5),and alpha-minimum essential medium(αMEM;n=5).Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group(P<0.05)and theαMEM group(P<0.01).Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA(0[control],1 mmol l−1,2 mmol l−1,and 5 mmol l−1)to determine the most effective concentration of 5-ALA.The 2 mmol l−15-ALA group(n=3)presented the highest positive rate of spermatogonial stem cells compared with those in the control,1 mmol l−1,and 5 mmol l−15-ALA groups.Finally,the tissue fragments were preserved in HBSS with control(n=3)and 2 mmol l−15-ALA(n=3)under low-temperature conditions.A comparative analysis was performed against fresh testes(n=3)to elucidate the underlying mechanism of 5-ALA.Gene set enrichment analysis(GSEA)for WikiPathways revealed that the p38 mitogen-activated protein kinase(MAPK)signaling pathway was downregulated in the 2 mmol l−15-ALA group compared with that in the control group(normalized enrichment score[NES]=−1.57,false discovery rate[FDR]=0.229,and P=0.019).In conclusion,these data suggest that using 2 mmol l−15-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.展开更多
The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health...The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.展开更多
The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspocha...The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspochalasins,templichalasins A-C(1-3),along with six known aspochalasins(4-9)were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045.Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system,while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons.Their structures were characterized through extensive spectroscopic analyses,electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analysis.Additionally,we demonstrated that compound 4 can be readily converted into compounds 1-3 under mild acidic conditions and proposed a plausible mechanism for this conversion.Bioactivity evaluation of compounds 1-9 against CVB3 revealed the inhibitory effects of all compounds against the virus.Notably,compound 9 exhibited superior antiviral activity,surpassing the commercial drug ribavirin in selectivity index(SI)value.展开更多
Porcine Contagious Pleuropneumonia(PCP)is a respiratory infectious disease of pigs caused by Actinobacillus pleuropneumoniae.The disease has been prevalent in pig farms since it was first identified in 1957(Pattison e...Porcine Contagious Pleuropneumonia(PCP)is a respiratory infectious disease of pigs caused by Actinobacillus pleuropneumoniae.The disease has been prevalent in pig farms since it was first identified in 1957(Pattison et al.1957).展开更多
Due to its broken out-of-plane symmetry,z-cut periodically poled lithium niobate(PPLN)has exhibited ultrahigh second-order optical nonlinearity.Precise quantification of the domain structure of z-cut PPLN plays a crit...Due to its broken out-of-plane symmetry,z-cut periodically poled lithium niobate(PPLN)has exhibited ultrahigh second-order optical nonlinearity.Precise quantification of the domain structure of z-cut PPLN plays a critical role during poling fabrication.To enhance the imaging detection efficiency of the domain structure in z-cut PPLN,we have developed a second-harmonic generation microscope system specifically designed to produce a longitudinal electric field in foci for the imaging domain inversion.We demonstrated that imaging using a longitudinal electric field can achieve a contrast ratio enhancement by a factor of 1.77,showing high imaging efficiency and making the proposed method suitable for in situ monitoring of the z-cut PPLN poling process.展开更多
BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up da...BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up data in a homogeneous population are required to understand these changes better.AIM To comprehensively evaluate changes in body composition and their prognostic value in patients with metastatic colorectal cancer undergoing palliative chemo-therapy.METHODS This retrospective study included patients with recurrent or metastatic colorectal cancer who received palliative chemotherapy between 2008 and 2017.Computed tomography scans were analyzed at multiple time points(before each new chemotherapy regimen and after discontinuing all chemotherapy).Body composition was analyzed from each scan using artificial intelligence software(AID-UTM,iAID Inc.),and its association with survival was evaluated through time-dependent Cox regression to adjust for time-varying effects.RESULTS This analysis included 1805 patients,with a median age at diagnosis of 57 years,and 62%were male.At first-line chemotherapy initiation,4.7%,30.9%,36.5%,and 37.1%of the patients had sarcopenia,myosteatosis,and visceral and subcutaneous obesity,respectively.During treatment,approximately 54.5%of the patients experienced significant changes in body composition,with 9.1%and 19.2%developing new sarcopenia and myosteatosis,respectively.Sarcopenia and myosteatosis were associated with poorer survival outcomes[hazard ratio(HR)for sarcopenia,2.55(95%CI:2.06-3.16,P<0.001;HR for myosteatosis,2.37(95%CI:2.00-2.82),P<0.001].In contrast,visceral and subcutaneous obesity were associated with improved survival[HR for visceral obesity,0.69(95%CI:0.57-0.82),P<0.001;HR for subcutaneous obesity,0.78(95%CI:0.64-0.95),P=0.015],with no negative impacts observed at higher fat levels.These changes correlated with end-of-life survival time.CONCLUSION Abnormalities and body composition changes were frequently observed during palliative chemotherapy for advanced colorectal cancer;myosteatosis was common.Comprehensive body composition assessment offers valuable prognostic insights without requiring additional testing.展开更多
Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound iso...Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound isolated from plant species of the genus Aloe,remain unidentified.Here,we investigated the protective effects of Alo against cecal ligation and puncture(CLP)-induced sepsis and microflora in mice.Alo significantly improved CLP-induced sepsis and the survival rate of septic mice,downregulated the expression of proinflammatory factors,and decreased the infiltration of inflammatory cells in tissues.Alo upregulated the proportion of peritoneal macrophages,reduced the number of peritoneal bacteria,decreased the content of short-chain fatty acids and bile acids in the abdominal cavity,and suppressed Toll-like receptor(TLR)-2/4/nuclear factor kappa-B(NF-κB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Caspase-1/3/8 signaling.Furthermore,Alo altered the composition of the microbiome and promoted the growth of Lactobacillus,which showed a stronger anti-inflammatory effect.Whole-genome analysis identified the genes Saa3,Il10,Fpr1,and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis.Overall,our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.展开更多
基金Supported by Natural Science Foundation of Guangdong Province of China,No.2024A1515012862.
文摘BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is a procedure used for patients with initially unresectable colorectal liver metastases(CRLM).However,the procedure has been reported to be associated with high morbidity and mortality.Laparoscopic ALPPS has recently been reported as a minimally invasive technique that reduces perioperative risks.AIM To assess the safety and feasibility of full laparoscopic ALPPS in patients with CRLM.METHODS A retrospective analysis was conducted on all consecutive patients with CRLM who underwent full laparoscopic ALPPS at the Sixth Affiliated Hospital of Sun Yat-sen University between March 2021 and July 2024.RESULTS Fifteen patients were included,13 with synchronous liver metastases.Nine patients had more than five liver tumors,with the highest count being 22.The median diameter of the largest lesion was 2.8 cm on preoperative imaging.No extrahepatic metastases were observed.RAS mutations were detected in nine patients,and 14 underwent preoperative chemotherapy.The median increase in future liver remnant volume during the interstage interval was 47.0%.All patients underwent R0 resection.Overall complication rates were 13.3%(stage 1)and 53.3%(stage 2),while major complication rates(Clavien-Dindo≥IIIa)were 13.3%(stage 1)and 33.3%(stage 2).No mortality occurred in either stage.The median hospital stay after stage 2 was 10 days.CONCLUSION Full laparoscopic ALPPS for CRLM is safe and feasible,with the potential for reduced morbidity and mortality,offering radical resection opportunities for patients with initially unresectable CRLM.
基金supported by the Deutsche Forschungsgemeinschaft(DFG),TRR274(Project ID 408885537,Sy Nergy,EXC 2145/ID 390857198,to FMB)。
文摘The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
文摘The field of biomedical imaging has been revolutionized by deep learning techniques.This special issue is focused on the theme of“AI-based Image Analysis”.Because there are so many conferences and journals in this field,our special issue can only be a small snapshot of a much bigger and highly dynamic picture.In this special issue,we present six papers that highlight the power of deep learning in solving challenging biomedical imaging and image analysis problems.
基金Supported by Instituto de Salud Carlos III(ISCiii),No.PI19/01266 and No.PI22/00857Consejería de Salud y Familias(Junta de Andalucía),No.PI-0216-2020 and No.PIP-0215-2020Biomedical Research Network Center for Liver and Digestive Diseases(CIBERehd)founded by the ISCIII and co-financed by European Regional Development Fund“A way to achieve Europe”ERDF.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of primary liver cancer with varied incidence and epidemiology worldwide.Sorafenib is still a recommended treatment for a large proportion of patients with advanced HCC.Different patterns of treatment responsiveness have been identified in differentiated hepatoblastoma HepG2 cells and metastatic HCC SNU449 cells.AIM To define the long non-codingRNA-microRNA-mRNA(lncRNA-miRNA-mRNA)predicted signatures related to selected hallmarks of cancer(apoptosis,autophagy,cell stress,cell dedifferentiation and invasiveness)in RNAseq studies using Sorafenib-treated HepG2 and SNU449 cells.Various available software analyses allowed us to establish the lncRNA-miRNA-mRNA regulatory axes following treatment in HepG2 and SNU449 cells.METHODS HepG2 and SNU449 cells were treated with Sorafenib(10μmol/L)for 24 hours.Total RNA,including small and long RNA,was extracted with a commercial miRNeasy kit.RNAseq was carried out for the identification of changes in lncRNA-miRNA-mRNA regulatory axes.RESULTS MALAT,THAP9-AS1 and SNGH17 appeared to coordinately regulate miR-374b-3p and miR-769-5p that led to upregulation of SMAD7,TIRARP,TFAP4 and FAXDC2 in HepG2 cells.SNHG12,EPB41 L4A-AS1,LINC01578,SNHG12 and GAS5 interacted with let-7b-3p,miR-195-5p and VEGFA in SNU449 cells.The axes MALAT1/hsamir-374b-3p/SMAD7 and MALAT1/hsa-mir-769-5p/TFAP4 were of high relevance for Sorafenib response in HepG2 cells,whereas PVT1/hsa-miR-195-5p/VEGFA was responsible for the differential response of SNU449 cells to Sorafenib treatment.CONCLUSION Critical lncRNAs acting as sponges of miRNA were identified that regulated mRNA expression,whose proteins mainly increased the antitumor effectiveness of the treatment(SMAD7,TIRARP,TFAP4,FAXDC2 and ADRB2).However,the broad regulatory axis leading to increased VEGFA expression may be related to the side effect of Sorafenib in SNU449 cells.
基金supported by grants PID2020-115823-GB100 funded by MCIN/AEI/10.13039/501100011033SBPLY/21/180501/000150 funded by JCCM/ERDF-A way of making Europe+1 种基金2022-GRIN-34354 grant by UCLM/ERDF intramural funding to LJDJDNL.DJ held a predoctoral fellowship granted by UCLM/ESF“Plan Propio de Investigación.”。
文摘Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
文摘AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR),and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS:A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital,Sun Yat-sen University from 2022 to 2023 were included,including 95 first-diagnosed DR patients and 105 patients without DR,and all patients underwent OCTA examination and a collection of demographics and renal function parameters.After a quality check,automated measurements of the foveal avascular zone area,vessel density(VD),and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS:Using random forest and multivariate Logistic regression methods,we developed a diagnostic model for DR based on 12 variables(age,FBG,SBP,DBP,HbA1c,ALT,ALP,urea/Scr,DM duration,HUA,DN,and CMT).Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window,AUC=0.837 vs 0.819,P=0.03).In the study of DN patients,the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD;outer VD;full VD;outer PD;full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model.Meanwhile,compared with the 3 mm×3 mm window,the microvascular parameters in the 6 mm×6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.
基金funded by Maranatha Christian University,Bandung,Indonesia for Productive Lecturer Research under grant number:011/SK/ADD/UKM/IV/2024.
文摘Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.
基金supported by the Charles University Cooperatio Program,Research Areas MED/DIAG,and Surgical Disciplinessupport from the Ministry of Education,Youth,and Sports of the Czech Republic under Project FIND No.CZ.02.1.01/0.0/0.0/16_019/0000787.L.V.was also supported by Charles University SVV-2025260773.
文摘Background : Scleral fixation of intraocular lenses is a surgical technique that involves anchoring an artificial lens to the sclera. Traditional approaches, such as capsular bag placement, may not be feasible in certain situations, making scleral fixation a valuable alternative. The scleral reactions to different types of suture materials are not fully understood. Therefore, the present study describes the microscopic structure of normal scleral tissue and its changes with suture materials. Methods : We compared six groups of rabbit eyes focusing on the sclera: group with polytetrafluoroethylene( PTFE) chain, PTFE fiber, polypropylene( PPE) fiber and control groups. multilevel sampling and stereological methods were used for histological quantification of the leukocyte infiltration fractions and type Ⅰ and type Ⅲ collagen. Results : Quantitative histological evaluation revealed the following:(1) For all materials used, inflammation was present in the surrounding scleral tissue compared with healthy controls. However, leukocyte infiltration in the sclera was not statistically different between the materials.(2) As part of the evaluation of collagen, the greatest changes occurred in the PTFE fiber group at 2 weeks postoperatively. In the PTFE chain group, more significant changes were visible at 4 weeks.(3) The changes in the PPE fiber group compared to healthy scleral tissue were the least significant. Conclusions : From a histological point of view, it is evident that there are differences in the quantitative parameters between the untouched sclera and the sclera with suture material. Furthermore, distinctions were observed among various materials and across different time intervals.
文摘BACKGROUND Rectal neuroendocrine tumors(NETs)smaller than 10 mm and well-differentiated tumors are generally considered to have a low risk of lymph node and distant metastasis,making them suitable for endoscopic resection.In contrast,tumors≥20 mm in size typically require surgical resection.However,the optimal management of intermediate-sized(10-15 mm)rectal NETs remains controversial.AIM To compare the clinical outcomes of endoscopic resection of rectal NETs<1 cm and those 1-1.5 cm in size.METHODS A retrospective study was conducted on 1056 patients with rectal NETs treated at the Samsung Medical Center between January 2005 and June 2021.After propensity score matching(1:10)for age,sex,and type of endoscopic resection,225 patients with tumors<1 cm in size and 27 patients with tumors 1-1.5 cm in size were analyzed.RESULTS Surgical resection was more frequent in the 1-1.5 cm group(37.2%)than in the<1 cm group(10.7%)(P<0.01).Endoscopic submucosal dissection was also more commonly performed in the 1-1.5 cm group(48.1%vs 18.5%,P<0.01).Negative resection margins were achieved in 97.2%of the patients,with no significant difference between the groups(P=0.22).No lymphovascular invasion was observed.During a median follow-up of 54 months,no recurrence occurred in the 1-1.5 cm group,while one case of metachronous recurrence was noted in the<1 cm group(P=1.00).There was no significant difference in recurrence-free survival(P=0.48).CONCLUSION Endoscopic resection of 1-1.5 cm grade 1 rectal NETs yielded comparable outcomes to those<1 cm in size,suggesting its feasibility as a treatment.
文摘BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are increasingly being used to treat type 2 diabetes mellitus(T2DM)and obesity.Although GLP-1RAs delay gastric emptying,their impact on gastric mucosal visibility during upper endoscopy remains uncertain,especially in Asian patients.AIM To investigate the association between GLP-1RA treatment and gastric mucosal visibility during upper endoscopy in Asian patients with T2DM.METHODS The study population included Korean patients who underwent esophagogastroduodenoscopy(EGD)with concomitant GLP-1RA or dipeptidyl peptidase 4 inhibitor(DPP4i)for the treatment of T2DM.A 1:2 propensity score matching between GLP-1RA and DPP4i users resulted in 198 matched patients and 295 matched patients in each group,respectively.Gastric mucosal visibility was assessed by reviewing endoscopy images with a validated scale(POLPREP).In addition,the rates of aborted and repeat EGD and pulmonary aspiration were also assessed.RESULTS Of the 493 matched patients,mean body mass index was 26.0 kg/m^(2).The rate of inadequate gastric mucosal visibility(gastric POLPREP score 0 or 1)was significantly higher in GLP-1RA group than matched DPP4i group(8.6%vs 1.4%,P=0.0007).The rates of aborted EGD and repeat EGD were also significantly higher in GLP-1RA than DPP4i group(7.6%vs 0.7%in both aborted and repeat EGD,P=0.0011).Multivariable logistic regression revealed GLP-1RA use as an independent risk factor for both inadequate gastric mucosal visibility(odds ratio=6.143,95%confidence interval:2.289,20.318,P=0.0008)and aborted EGD(odds ratio=11.099,95%confidence interval:3.172,63.760,P=0.0010).Despite gastric residue,no pulmonary aspiration was reported in either group.CONCLUSION GLP-1RA use was associated with a higher risk of inadequate gastric mucosal visibility and aborted and repeat procedures during upper gastrointestinal endoscopy in Korean patients with T2DM while pulmonary aspiration was not observed.
基金funded by the National Natural Science Foundation of China(No.81971759 and No.82171604)the Guangdong Basic and Applied Basic Research Foundation(2023B1515020108)+3 种基金the Science and Technology Program of Guangzhou(202206010089)the Excellent Talents Training Project of The Sixth Affiliated Hospital of Sun Yat-sen University(R20210217202601970)the Postdoctoral Fellowship Program of CPSF(GZC20233216)the Basic and Applied Basic Research Foundation of Guangdong Province(2021A1515111195).
文摘The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid(5-ALA).Furthermore,this study aimed to explore the underlying mechanism of the protective effects of 5-ALA.First,we collected and stored mouse testicular fragments in different media,including Hank’s balanced salt solution(HBSS;n=5),Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F12;n=5),and alpha-minimum essential medium(αMEM;n=5).Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group(P<0.05)and theαMEM group(P<0.01).Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA(0[control],1 mmol l−1,2 mmol l−1,and 5 mmol l−1)to determine the most effective concentration of 5-ALA.The 2 mmol l−15-ALA group(n=3)presented the highest positive rate of spermatogonial stem cells compared with those in the control,1 mmol l−1,and 5 mmol l−15-ALA groups.Finally,the tissue fragments were preserved in HBSS with control(n=3)and 2 mmol l−15-ALA(n=3)under low-temperature conditions.A comparative analysis was performed against fresh testes(n=3)to elucidate the underlying mechanism of 5-ALA.Gene set enrichment analysis(GSEA)for WikiPathways revealed that the p38 mitogen-activated protein kinase(MAPK)signaling pathway was downregulated in the 2 mmol l−15-ALA group compared with that in the control group(normalized enrichment score[NES]=−1.57,false discovery rate[FDR]=0.229,and P=0.019).In conclusion,these data suggest that using 2 mmol l−15-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
基金American Heart Association Award,No.24IVPHA1288417and FCT Fellowships,No.2022.13253.BDANA.
文摘The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.
基金supported by the National Natural Science Foundation of China(Nos.31972852,32371496,and 81903527)the Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(No.2060302)。
文摘The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspochalasins,templichalasins A-C(1-3),along with six known aspochalasins(4-9)were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045.Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system,while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons.Their structures were characterized through extensive spectroscopic analyses,electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analysis.Additionally,we demonstrated that compound 4 can be readily converted into compounds 1-3 under mild acidic conditions and proposed a plausible mechanism for this conversion.Bioactivity evaluation of compounds 1-9 against CVB3 revealed the inhibitory effects of all compounds against the virus.Notably,compound 9 exhibited superior antiviral activity,surpassing the commercial drug ribavirin in selectivity index(SI)value.
基金supported by the University-Industry Col aborative Education Program,China(220904860093831)。
文摘Porcine Contagious Pleuropneumonia(PCP)is a respiratory infectious disease of pigs caused by Actinobacillus pleuropneumoniae.The disease has been prevalent in pig farms since it was first identified in 1957(Pattison et al.1957).
基金supported by the National Key Research and Development Program of China(Grant Nos.2022YFC3401100 and 2022YFF0712500)the Guangdong Major Project of Basic and Applied Basic Research(Grant No.2020B0301030009)+2 种基金the National Natural Science Foundation of China(Grant Nos.12204017,12004012,12004013,12041602,91750203,91850111,and 92150301)the China Postdoctoral Science Foundation(Grant No.2020M680220 and 2020M680230)the Clinical Medicine Plus X-Young Scholars Project,Peking University,Fundamental Research Funds for the Central Universities.
文摘Due to its broken out-of-plane symmetry,z-cut periodically poled lithium niobate(PPLN)has exhibited ultrahigh second-order optical nonlinearity.Precise quantification of the domain structure of z-cut PPLN plays a critical role during poling fabrication.To enhance the imaging detection efficiency of the domain structure in z-cut PPLN,we have developed a second-harmonic generation microscope system specifically designed to produce a longitudinal electric field in foci for the imaging domain inversion.We demonstrated that imaging using a longitudinal electric field can achieve a contrast ratio enhancement by a factor of 1.77,showing high imaging efficiency and making the proposed method suitable for in situ monitoring of the z-cut PPLN poling process.
基金Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,by the Ministry of Health&Welfare,Republic of Korea,No.RS-2018-KH049509the 2022 Cancer Research Support Project from the Korea Foundation for Cancer Research,No.CB-2022-A-3.
文摘BACKGROUND In patients with metastatic colorectal cancer,chemotherapy may lead to changes in body composition,including skeletal muscle quantity and quality,and body fat area and distribution.Longitudinal follow-up data in a homogeneous population are required to understand these changes better.AIM To comprehensively evaluate changes in body composition and their prognostic value in patients with metastatic colorectal cancer undergoing palliative chemo-therapy.METHODS This retrospective study included patients with recurrent or metastatic colorectal cancer who received palliative chemotherapy between 2008 and 2017.Computed tomography scans were analyzed at multiple time points(before each new chemotherapy regimen and after discontinuing all chemotherapy).Body composition was analyzed from each scan using artificial intelligence software(AID-UTM,iAID Inc.),and its association with survival was evaluated through time-dependent Cox regression to adjust for time-varying effects.RESULTS This analysis included 1805 patients,with a median age at diagnosis of 57 years,and 62%were male.At first-line chemotherapy initiation,4.7%,30.9%,36.5%,and 37.1%of the patients had sarcopenia,myosteatosis,and visceral and subcutaneous obesity,respectively.During treatment,approximately 54.5%of the patients experienced significant changes in body composition,with 9.1%and 19.2%developing new sarcopenia and myosteatosis,respectively.Sarcopenia and myosteatosis were associated with poorer survival outcomes[hazard ratio(HR)for sarcopenia,2.55(95%CI:2.06-3.16,P<0.001;HR for myosteatosis,2.37(95%CI:2.00-2.82),P<0.001].In contrast,visceral and subcutaneous obesity were associated with improved survival[HR for visceral obesity,0.69(95%CI:0.57-0.82),P<0.001;HR for subcutaneous obesity,0.78(95%CI:0.64-0.95),P=0.015],with no negative impacts observed at higher fat levels.These changes correlated with end-of-life survival time.CONCLUSION Abnormalities and body composition changes were frequently observed during palliative chemotherapy for advanced colorectal cancer;myosteatosis was common.Comprehensive body composition assessment offers valuable prognostic insights without requiring additional testing.
基金supported by the National Natural Science Foundation of China(81803547)the Natural Science Foundation of Fujian Province,China(2021J01204)Fujian Provincial Regional Development Project(2021N3005)。
文摘Most Aloe species are used as new food or functional food ingredient.Even though widely known for its health benefits,the anti-inflammatory effects and underlying mechanisms of Aloin(Alo),an anthraquinone compound isolated from plant species of the genus Aloe,remain unidentified.Here,we investigated the protective effects of Alo against cecal ligation and puncture(CLP)-induced sepsis and microflora in mice.Alo significantly improved CLP-induced sepsis and the survival rate of septic mice,downregulated the expression of proinflammatory factors,and decreased the infiltration of inflammatory cells in tissues.Alo upregulated the proportion of peritoneal macrophages,reduced the number of peritoneal bacteria,decreased the content of short-chain fatty acids and bile acids in the abdominal cavity,and suppressed Toll-like receptor(TLR)-2/4/nuclear factor kappa-B(NF-κB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Caspase-1/3/8 signaling.Furthermore,Alo altered the composition of the microbiome and promoted the growth of Lactobacillus,which showed a stronger anti-inflammatory effect.Whole-genome analysis identified the genes Saa3,Il10,Fpr1,and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis.Overall,our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.
