In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they s...In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver cancer.Although the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.展开更多
Survival rates following radical surgery for gastric neuroendocrine neoplasms(g-NENs)are low,with high recurrence rates.This fact impacts patient prognosis and complicates postoperative management.Traditional prognost...Survival rates following radical surgery for gastric neuroendocrine neoplasms(g-NENs)are low,with high recurrence rates.This fact impacts patient prognosis and complicates postoperative management.Traditional prognostic models,including the Cox proportional hazards(CoxPH)model,have shown limited predictive power for postoperative survival in gastrointestinal neuroectodermal tumor patients.Machine learning methods offer a unique opportunity to analyze complex relationships within datasets,providing tools and methodologies to assess large volumes of high-dimensional,multimodal data generated by biological sciences.These methods show promise in predicting outcomes across various medical disciplines.In the context of g-NENs,utilizing machine learning to predict survival outcomes holds potential for personalized postoperative management strategies.This editorial reviews a study exploring the advantages and effectiveness of the random survival forest(RSF)model,using the lymph node ratio(LNR),in predicting disease-specific survival(DSS)in postoperative g-NEN patients stratified into low-risk and high-risk groups.The findings demonstrate that the RSF model,incorporating LNR,outperformed the CoxPH model in predicting DSS and constitutes an important step towards precision medicine.展开更多
Aim: Recently, the role of feeding coparenting has gained attention in the child eating research field. The Feeding Coparenting Scale (FCS), a measure of how caregivers interact with their partners when feeding their ...Aim: Recently, the role of feeding coparenting has gained attention in the child eating research field. The Feeding Coparenting Scale (FCS), a measure of how caregivers interact with their partners when feeding their children was developed in the United States in 2019. However, there is no valid and reliable measure to assess feeding coparenting among caregivers of school-aged children in Japan. Therefore, this study aimed to develop a Japanese version of the FCS (FCS-J) questionnaire for caregivers with school-aged children. Methods: This was a web-based cross-sectional survey completed by caregivers of children aged 10-12 years. A preliminary survey using interviews and a web-based survey was conducted and found that the translated items of the FCS into Japanese were understandable to Japanese people. The developed survey was administered to parents of children at an elementary school. The reliability of the survey was assessed using both test-retest reliability and internal consistency analysis. Exploratory factor analysis was used to test construct validity, and known population validity was examined in relation to attributes, marital satisfaction, and feeding tasks. Results: Findings with 135 parents of school-aged children showed good internal reliability and validity of the FCS-J. The mean score for the overall FCS-J score was 46.2 (SD = 6.2), with Cronbach’s α of 0.72. For the subscales, Cronbach’s α ranged from 0.75 to 0.79. In sum, the present study’s results support the three-factor structure of the FCS in Japanese caregivers in Japan. Conclusions: The developed FCS-J was found to have a certain degree of reliability and validity. In this study, a Japanese version of the FCS-J was developed. .展开更多
BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of...BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.展开更多
α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition...α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.展开更多
BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety ...BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.展开更多
The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neur...The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.展开更多
Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,...Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.展开更多
Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,g...Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.展开更多
Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric studies.To utilize this knowledge for non-contact A...Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric studies.To utilize this knowledge for non-contact ACL injury prevention in sports,it is necessary to elucidate how the ground reaction force(GRF)acting point(center of pressure(CoP))in the stance foot produces combined knee VL+IR moments in risky maneuvers,such as cuttings.However,the effects of the GRF acting point on the development of the combined knee VL+IR moment in cutting are still unknown.Methods:We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector’s directional probability for developing the combined knee VL+IR moment,and theoretically predicted that when the CoP is posterior to the tibial rotational axis,the GRF vector is more likely to produce the combined knee VL+IR moment than when the CoP is anterior to the tibial rotational axis.Then,we tested a stochastic aspect of our theory in a lab-controlled in vivo experiment.Fourteen females performed 60˚cutting under forefoot/rearfoot strike conditions(10 trials each).The positions of lower limb markers and GRF data were measured,and the knee moment due to GRF vector was calculated.The trials were divided into anterior-and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike,and the occurrence rate of the combined knee VL+IR moment was compared between trial groups.Results:The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL+IR moment(maximum of 82.8%)at every time point than those of the anterior-CoP trials,as theoretically predicted by the deterministic mechanical condition.Conclusion:The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the combined knee VL+IR stress.展开更多
In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD patho...In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.展开更多
BACKGROUND Venous thromboembolism(VTE)is a potentially fatal complication of hepatectomy.The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the...BACKGROUND Venous thromboembolism(VTE)is a potentially fatal complication of hepatectomy.The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding.Therefore,we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy.AIM To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy.METHODS The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed.Patients were divided into two groups according to whether or not they developed VTE after hepatectomy,as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities.Clinicopathological factors,including demographic data and perioperative D-dimer values,were compared between the two groups.Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value.Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors.RESULTS In total,234 patients who underwent hepatectomy were,of whom(5.6%)were diagnosed with VTE following hepatectomy.A comparison between the two groups showed significant differences in operative time(529 vs 403 min,P=0.0274)and blood loss(530 vs 138 mL,P=0.0067).The D-dimer levels on postoperative days(POD)1,3,5,7 were significantly higher in the VTE group than in the non-VTE group.In the multivariate analysis,intraoperative blood loss of>275 mL[odds ratio(OR)=5.32,95%confidence interval(CI):1.05-27.0,P=0.044]and plasma D-dimer levels on POD 5≥21μg/mL(OR=10.1,95%CI:2.04-50.1,P=0.0046)were independent risk factors for VTE after hepatectomy.CONCLUSION Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.展开更多
BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby cons...BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby considerably reducing the quality of life of females.Given the continuum in weakened ovarian function,progressing from incipient ovarian failure(IOF)to transitional ovarian failure and further to POI,it is necessary to develop biomarkers for predicting POI.The oxidative stress states in IOF and POI were comprehensively evaluated via oxidative stress[diacron-reactive oxygen metabolites(d-ROMs)]test and anti-oxidant capacity[biological antioxidant potential(BAP)].METHODS Females presenting with secondary amenorrhea over 4 mo and a follicle stimulating hormone level of>40 mIU/mL were categorized into the POI group.Females presenting with a normal menstrual cycle and a follicle stimulating hormone level of>10.2 mIU/mL were categorized into the IOF group.Healthy females without ovarian hypofunction were categorized into the control group.Among females aged<40 years who visited our hospital from January 2021 to June 2022,we recruited 11 patients into both POI and IOF groups.For the potential antioxidant capacity,the relative oxidative stress index(BAP/d-ROMs×100)was calculated,and the oxidative stress defense system was comprehensively evaluated.RESULTS d-ROMs were significantly higher in the POI and IOF groups than in the control group,(478.2±58.7 U.CARR,434.5±60.6 U.CARR,and 341.1±35.1 U.CARR,respectively)(U.CARR is equivalent to 0.08 mg/dL of hydrogen peroxide).However,no significant difference was found between the POI and IOF groups.Regarding BAP,no significant difference was found between the control,IOF,and POI groups(2078.5±157.4μmol/L,2116.2±240.2μmol/L,and 2029.0±186.4μmol/L,respectively).The oxidative stress index was significantly higher in the POI and IOF groups than in the control group(23.7±3.3,20.7±3.6,and 16.5±2.1,respectively).However,no significant difference was found between the POI and IOF groups.CONCLUSION High levels of oxidative stress suggest that evaluating the oxidative stress state may be a useful indicator for the early detection of POI.展开更多
Objective:The aim of this research was to evaluate the efficiency of reciprocating morcellation for removing giant benign prostatic hyperplasia during holmium laser enucleation of the prostate,investigate whether perf...Objective:The aim of this research was to evaluate the efficiency of reciprocating morcellation for removing giant benign prostatic hyperplasia during holmium laser enucleation of the prostate,investigate whether performing morcellation as a two-stage procedure improves tissue retrieval efficiency,and seek to determine the optimal interval between the two surgeries.Methods:This study included nine cases of holmium laser enucleation of the prostate with an enucleated prostate weight exceeding 200 g,indicative of substantial prostate enlargement.Morcellation was performed on Day 0(n=4),Day 4(n=1),Day 6(n=1),and Day 7(n=3).The intervals were compared regarding the morcellation efficiency,beach ball presence,and pathology.Results:The mean estimated prostate volume was 383(range 330e528)mL;the median enucleation weight was 252(interquartile range[IQR]222,342)g;and the median enucleation time was 83(IQR 62,100)min.The mean morcellation efficiency was 1.44(SD 0.55)g/min on Day 0 and 13.69(SD 2.46)g/min on day 7.The morcellation efficiency was 4.15 g/min and 10.50 g/min on Day 4 and Day 6,respectively,with significantly higher in the two-stage group compared to one-stage group(11.0 g/min vs.1.5 g/min;p=0.014).Efficiency was strongly correlated with intervals(p<0.001);the incidences of beach balls were 100%(4/4)and 60%(3/5)in the immediate and two-stage surgery groups,respectively.Conclusion:The efficiency of two-stage morcellation with reciprocating morcellators was highly related to the postoperative interval,with the maximum efficiency reached on Day 7.展开更多
Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junc...Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.展开更多
BACKGROUND Several studies have explored the long-term prognosis of patients with asymp-tomatic gallbladder stones.These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cas...BACKGROUND Several studies have explored the long-term prognosis of patients with asymp-tomatic gallbladder stones.These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases.AIM To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities.METHODS We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022.When symptoms developed,patients were transferred to hospitals where appropriate treatment was possible.We investigated the asymptomatic and survival periods during the follow-up.RESULTS Among the 237 patients,214(90.3%)remained asymptomatic,with a mean asymptomatic period of 3898.9279±46.871 d(50-4111 d,10.7 years on average).Biliary complications developed in 23 patients(9.7%),with a mean survival period of 4010.0285±31.2788 d(53-4112 d,10.9 years on average).No patient died of biliary complications.CONCLUSION The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable.When the condition became symptomatic,the patients were transferred to hospitals with beds that could address it;thus,no deaths related to biliary complications were reported.This finding suggests that follow-up care in clinics without beds is possible.展开更多
Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the...Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.展开更多
BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of...BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.展开更多
Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the...Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear.To address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts.In these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was upregulated.Moreover,the expression of EMT-related transcription factors,including Slug,was elevated.On the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones.These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic changes.Moreover,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene transcription.These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.展开更多
DNAX-associated protein 12 kD size(DAP12)is a dominant immunoreceptor tyrosine-based activation motif(ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis.Although several DAP1...DNAX-associated protein 12 kD size(DAP12)is a dominant immunoreceptor tyrosine-based activation motif(ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis.Although several DAP12-associated receptors(DARs)have been identified in osteoclasts,including triggering receptor expressed on myeloid cells 2(TREM-2),C-type lectin member 5 A(CLEC5A),and sialic acid-binding Ig-like lectin(Siglec)-15,their precise role in the development of osteoclasts and bone remodeling remain poorly understood.In this study,mice deficient in Trem-2,Clec5a,Siglec-15 were generated.展开更多
基金Supported by Japan Society for the Promotion of Science,No.23K07347。
文摘In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver cancer.Although the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.
文摘Survival rates following radical surgery for gastric neuroendocrine neoplasms(g-NENs)are low,with high recurrence rates.This fact impacts patient prognosis and complicates postoperative management.Traditional prognostic models,including the Cox proportional hazards(CoxPH)model,have shown limited predictive power for postoperative survival in gastrointestinal neuroectodermal tumor patients.Machine learning methods offer a unique opportunity to analyze complex relationships within datasets,providing tools and methodologies to assess large volumes of high-dimensional,multimodal data generated by biological sciences.These methods show promise in predicting outcomes across various medical disciplines.In the context of g-NENs,utilizing machine learning to predict survival outcomes holds potential for personalized postoperative management strategies.This editorial reviews a study exploring the advantages and effectiveness of the random survival forest(RSF)model,using the lymph node ratio(LNR),in predicting disease-specific survival(DSS)in postoperative g-NEN patients stratified into low-risk and high-risk groups.The findings demonstrate that the RSF model,incorporating LNR,outperformed the CoxPH model in predicting DSS and constitutes an important step towards precision medicine.
文摘Aim: Recently, the role of feeding coparenting has gained attention in the child eating research field. The Feeding Coparenting Scale (FCS), a measure of how caregivers interact with their partners when feeding their children was developed in the United States in 2019. However, there is no valid and reliable measure to assess feeding coparenting among caregivers of school-aged children in Japan. Therefore, this study aimed to develop a Japanese version of the FCS (FCS-J) questionnaire for caregivers with school-aged children. Methods: This was a web-based cross-sectional survey completed by caregivers of children aged 10-12 years. A preliminary survey using interviews and a web-based survey was conducted and found that the translated items of the FCS into Japanese were understandable to Japanese people. The developed survey was administered to parents of children at an elementary school. The reliability of the survey was assessed using both test-retest reliability and internal consistency analysis. Exploratory factor analysis was used to test construct validity, and known population validity was examined in relation to attributes, marital satisfaction, and feeding tasks. Results: Findings with 135 parents of school-aged children showed good internal reliability and validity of the FCS-J. The mean score for the overall FCS-J score was 46.2 (SD = 6.2), with Cronbach’s α of 0.72. For the subscales, Cronbach’s α ranged from 0.75 to 0.79. In sum, the present study’s results support the three-factor structure of the FCS in Japanese caregivers in Japan. Conclusions: The developed FCS-J was found to have a certain degree of reliability and validity. In this study, a Japanese version of the FCS-J was developed. .
基金the Foundation for Cancer Research supported by Kyoto Preventive Medical Center and the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid KAKENHI,No.JP 22K21080.
文摘BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.
基金supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region,Nos.2022GXNSFAA035622(to MJ),2020GXNSFAA297048(to ZZ)the National Natural Science Foundation of China,No.82060268(to ZZ)。
文摘α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.
文摘BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.
基金supported by the Uehara Memorial Foundation,JSPS under the Joint Research Program implemented in association with SNSF(JRPs),Grant No.JPJSJRP20221507 and KAKENHI Grant No.22K15711,JST FOREST Program(Grant No.JPMJFR2269,Japan)2022 iPS Academia Japan Grant,Life Science Foundation of Japan,Kato Memorial Bioscience Foundation,THE YUKIHIKO MIYATA MEMORIAL TRUST FOR ALS RESEARCH,the ICHIRO KANEHARA FOUNDATION,Takeda Science Foundation,and the YAMAGUCHI UNIVERSITY FUNDATION(all to HN).
文摘The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.
基金supported by KAKENHI under grant number 23K08535,22K09274(to MK)。
文摘Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
基金funded by Taiju Life Social Welfare Foundation(to HS).
文摘Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.
基金supported by the Grant-in-Aid for Young Scientists(B)Project(Grant No.24700716)funded by the Ministry of Education,Culture,Sports,Science and Technology,Japan.
文摘Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric studies.To utilize this knowledge for non-contact ACL injury prevention in sports,it is necessary to elucidate how the ground reaction force(GRF)acting point(center of pressure(CoP))in the stance foot produces combined knee VL+IR moments in risky maneuvers,such as cuttings.However,the effects of the GRF acting point on the development of the combined knee VL+IR moment in cutting are still unknown.Methods:We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector’s directional probability for developing the combined knee VL+IR moment,and theoretically predicted that when the CoP is posterior to the tibial rotational axis,the GRF vector is more likely to produce the combined knee VL+IR moment than when the CoP is anterior to the tibial rotational axis.Then,we tested a stochastic aspect of our theory in a lab-controlled in vivo experiment.Fourteen females performed 60˚cutting under forefoot/rearfoot strike conditions(10 trials each).The positions of lower limb markers and GRF data were measured,and the knee moment due to GRF vector was calculated.The trials were divided into anterior-and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike,and the occurrence rate of the combined knee VL+IR moment was compared between trial groups.Results:The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL+IR moment(maximum of 82.8%)at every time point than those of the anterior-CoP trials,as theoretically predicted by the deterministic mechanical condition.Conclusion:The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the combined knee VL+IR stress.
文摘In this article, we present our previous research, which highlighted adenosine triphosphate(ATP) as the cause of neuropathic pain during the acute phase of neuromyelitis optica spectrum disorder(NMOSD). In NMOSD pathology, damageassociated molecular patterns(DAMPs), including ATP, are released from damaged astrocytes, triggering the activation of innate immune cells. ATP is a central mediator of acute pain in NMOSD.
基金This study was reviewed and approved by the Ethics Committee of the Kobe University Graduate School of Medicine(Provided ID Number:B210306).
文摘BACKGROUND Venous thromboembolism(VTE)is a potentially fatal complication of hepatectomy.The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding.Therefore,we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy.AIM To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy.METHODS The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed.Patients were divided into two groups according to whether or not they developed VTE after hepatectomy,as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities.Clinicopathological factors,including demographic data and perioperative D-dimer values,were compared between the two groups.Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value.Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors.RESULTS In total,234 patients who underwent hepatectomy were,of whom(5.6%)were diagnosed with VTE following hepatectomy.A comparison between the two groups showed significant differences in operative time(529 vs 403 min,P=0.0274)and blood loss(530 vs 138 mL,P=0.0067).The D-dimer levels on postoperative days(POD)1,3,5,7 were significantly higher in the VTE group than in the non-VTE group.In the multivariate analysis,intraoperative blood loss of>275 mL[odds ratio(OR)=5.32,95%confidence interval(CI):1.05-27.0,P=0.044]and plasma D-dimer levels on POD 5≥21μg/mL(OR=10.1,95%CI:2.04-50.1,P=0.0046)were independent risk factors for VTE after hepatectomy.CONCLUSION Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.
文摘BACKGROUND Premature ovarian insufficiency(POI)is a condition that causes secondary amenorrhea owing to ovarian hypofunction at an early stage.Early follicular depletion results in intractable infertility,thereby considerably reducing the quality of life of females.Given the continuum in weakened ovarian function,progressing from incipient ovarian failure(IOF)to transitional ovarian failure and further to POI,it is necessary to develop biomarkers for predicting POI.The oxidative stress states in IOF and POI were comprehensively evaluated via oxidative stress[diacron-reactive oxygen metabolites(d-ROMs)]test and anti-oxidant capacity[biological antioxidant potential(BAP)].METHODS Females presenting with secondary amenorrhea over 4 mo and a follicle stimulating hormone level of>40 mIU/mL were categorized into the POI group.Females presenting with a normal menstrual cycle and a follicle stimulating hormone level of>10.2 mIU/mL were categorized into the IOF group.Healthy females without ovarian hypofunction were categorized into the control group.Among females aged<40 years who visited our hospital from January 2021 to June 2022,we recruited 11 patients into both POI and IOF groups.For the potential antioxidant capacity,the relative oxidative stress index(BAP/d-ROMs×100)was calculated,and the oxidative stress defense system was comprehensively evaluated.RESULTS d-ROMs were significantly higher in the POI and IOF groups than in the control group,(478.2±58.7 U.CARR,434.5±60.6 U.CARR,and 341.1±35.1 U.CARR,respectively)(U.CARR is equivalent to 0.08 mg/dL of hydrogen peroxide).However,no significant difference was found between the POI and IOF groups.Regarding BAP,no significant difference was found between the control,IOF,and POI groups(2078.5±157.4μmol/L,2116.2±240.2μmol/L,and 2029.0±186.4μmol/L,respectively).The oxidative stress index was significantly higher in the POI and IOF groups than in the control group(23.7±3.3,20.7±3.6,and 16.5±2.1,respectively).However,no significant difference was found between the POI and IOF groups.CONCLUSION High levels of oxidative stress suggest that evaluating the oxidative stress state may be a useful indicator for the early detection of POI.
文摘Objective:The aim of this research was to evaluate the efficiency of reciprocating morcellation for removing giant benign prostatic hyperplasia during holmium laser enucleation of the prostate,investigate whether performing morcellation as a two-stage procedure improves tissue retrieval efficiency,and seek to determine the optimal interval between the two surgeries.Methods:This study included nine cases of holmium laser enucleation of the prostate with an enucleated prostate weight exceeding 200 g,indicative of substantial prostate enlargement.Morcellation was performed on Day 0(n=4),Day 4(n=1),Day 6(n=1),and Day 7(n=3).The intervals were compared regarding the morcellation efficiency,beach ball presence,and pathology.Results:The mean estimated prostate volume was 383(range 330e528)mL;the median enucleation weight was 252(interquartile range[IQR]222,342)g;and the median enucleation time was 83(IQR 62,100)min.The mean morcellation efficiency was 1.44(SD 0.55)g/min on Day 0 and 13.69(SD 2.46)g/min on day 7.The morcellation efficiency was 4.15 g/min and 10.50 g/min on Day 4 and Day 6,respectively,with significantly higher in the two-stage group compared to one-stage group(11.0 g/min vs.1.5 g/min;p=0.014).Efficiency was strongly correlated with intervals(p<0.001);the incidences of beach balls were 100%(4/4)and 60%(3/5)in the immediate and two-stage surgery groups,respectively.Conclusion:The efficiency of two-stage morcellation with reciprocating morcellators was highly related to the postoperative interval,with the maximum efficiency reached on Day 7.
基金funded by JSPS KAKENHI Grant Numbers JP26290015 and JP21H02655(to TK)from Ministry of Education,Culture,Sports,Science,and Technology of Japan(MEXT)。
文摘Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.
文摘BACKGROUND Several studies have explored the long-term prognosis of patients with asymp-tomatic gallbladder stones.These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases.AIM To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities.METHODS We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022.When symptoms developed,patients were transferred to hospitals where appropriate treatment was possible.We investigated the asymptomatic and survival periods during the follow-up.RESULTS Among the 237 patients,214(90.3%)remained asymptomatic,with a mean asymptomatic period of 3898.9279±46.871 d(50-4111 d,10.7 years on average).Biliary complications developed in 23 patients(9.7%),with a mean survival period of 4010.0285±31.2788 d(53-4112 d,10.9 years on average).No patient died of biliary complications.CONCLUSION The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable.When the condition became symptomatic,the patients were transferred to hospitals with beds that could address it;thus,no deaths related to biliary complications were reported.This finding suggests that follow-up care in clinics without beds is possible.
基金supported by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science(15H04730,16H05186,16K08772,17K12004,19H03467,21J00572)a contract research fund from the Japan Program for Infectious Diseases Research and Infrastructure for research on emerging and re-emerging infectious diseases provided by the Japan Agency for Medical Research and Development(AMED)the Project for Promoting Leading-edge Research in Oral Science at Tokyo Medical and Dental University。
文摘Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.
文摘BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.
基金the Japan Society for the Promotion of Science(JSPS),KAKENHI,Grant Number 26350974.
文摘Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear.To address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts.In these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was upregulated.Moreover,the expression of EMT-related transcription factors,including Slug,was elevated.On the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones.These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic changes.Moreover,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene transcription.These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.
基金supported by a Grant-in-Aid for Exploratory Research from the Ministry of Education,Culture,Sports,Science,and Technology of Japan 17H04309 (MT)the Mitsubishi foundation。
文摘DNAX-associated protein 12 kD size(DAP12)is a dominant immunoreceptor tyrosine-based activation motif(ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis.Although several DAP12-associated receptors(DARs)have been identified in osteoclasts,including triggering receptor expressed on myeloid cells 2(TREM-2),C-type lectin member 5 A(CLEC5A),and sialic acid-binding Ig-like lectin(Siglec)-15,their precise role in the development of osteoclasts and bone remodeling remain poorly understood.In this study,mice deficient in Trem-2,Clec5a,Siglec-15 were generated.
