Anti-N-methyl-D-aspartate receptor-associated encephalitis(NMDARE)is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction.The mecha...Anti-N-methyl-D-aspartate receptor-associated encephalitis(NMDARE)is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction.The mechanism of pathogenesis remains incompletely understood,but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways.Young adults are most frequently affected;the median age at diagnosis is 21 years.There is a strong female predilection with a female sex predominance of 4:1.NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma.However,NMDARE has also been described in patients with small cell lung cancer,clear cell renal carcinoma,and other benign and malignant neoplasms.Diagnosis is based on correlation of the clinical presentation,electro-encephalography,laboratory studies,and imaging.Computed tomography,positron emission tomography,and magnetic resonance imaging are essential to identify an underlying tumor,exclude clinicopathologic mimics,and predict the likelihood of long-term functional impairment.Nuclear imaging may be of value for prognostication and to assess the response to therapy.Treatment may involve high-dose corticosteroids,intravenous immunoglobulin,and plasma exchange.Herein,we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria,treatment regimens,and proposed pathogenetic mechanisms.展开更多
BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory def...BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory deficits,among others.However,laryngospasm is rare.We present the case of a patient with anti-NMDAR antibodies and severe laryngospasms.CASE SUMMARY The patient was a 15-year-old female with normal psychomotor development.She was initially admitted to our neurological intensive care unit with seizures.She received anti-epilepsy treatment,and the seizures disappeared.However,2 wk later,she developed behavioral problems and speech impairment.Then,she developed severe laryngospasms,which were treated with intubation and a tracheotomy.Antibodies against the NMDAR were detected in the patient’s cerebrospinal fluid.Therefore,she was diagnosed with anti-NMDAR encephalitis.In addition,she received intravenously administered immunoglobulins,and methylprednisolone was administered.The patient’s symptoms gradually improved,and she was discharged from our hospital.Approximately 9 mo later,the patient could speak sentences,walk independently,and carry out activities of daily living independently.Through our case report,we highlighted laryngospasm as an uncommon presentation in patients with anti-NMDAR encephalitis.CONCLUSION Laryngospasm may be an uncommon clinical manifestation of anti-NMDAR encephalitis.展开更多
BACKGROUND Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a rare but important complication of ovarian teratoma.Between July 2012 and December 2019,six patients with ovarian teratoma-associated anti-NMDAR en...BACKGROUND Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a rare but important complication of ovarian teratoma.Between July 2012 and December 2019,six patients with ovarian teratoma-associated anti-NMDAR encephalitis were enrolled in our hospital and their clinical characteristics,treatment,and follow-up were reviewed.We also conducted a systematic literature review of ovarian teratoma related anti-NMDAR encephalitis reports between January 2014 and December 2019.AIM To better understand anti-NMDAR encephalitis through literature review and patients enrolled in our hospital.METHODS The six patients enrolled in the study were those diagnosed with anti-NMDAR encephalitis.Their history,clinical manifestations,and medications were recorded and optimum treatment provided in addition to maintaining a record of the follow-ups.In addition,we also extensively surveyed the literature and provide summarized data from 155 published cases of anti-NMDAR encephalitis from 130 case reports.PubMed and Scopus were the sources of these publications and the time period covered was 6 years ranging from January 2014 through December 2019.RESULTS The six patients enrolled for this study presented with typical symptoms resulting in a diagnosis of ovarian teratoma induced anti-NMDAR encephalitis.Appropriate interventions led to a positive outcome in all the patients,with five of six patients reporting full recovery and the sixth patient recovering with a few deficits.No death was recorded.The literature survey comprising of 155 patients cases across 130 case reports of anti-NMDAR encephalitis clearly indicated an upward trend in the reports/diagnosis in China,particularly in the surveyed time from 2014 through 2019.The majority of patients(150/155)underwent surgical intervention resulting in positive outcome.No treatment intervention was mentioned for one case while the four patients who were not surgically operated succumbed to the disease.CONCLUSION Suspected anti-NMDAR encephalitis should be quickly evaluated for anti-NMDAR antibodies since early diagnosis is important.In case of a tumor,its earliest and complete removal is recommended.Finally,early use of corticosteroids and IgG-depleting strategies(intravenous immunoglobulin or plasma exchange)may improve outcome.展开更多
Objective:An increasing number of pediatric patients are being diagnosed with anti-N-methyl-Daspartate receptor(NMDAR)encephalitis,whose treatment requires immunotherapy through nursing interventions.This study aimed ...Objective:An increasing number of pediatric patients are being diagnosed with anti-N-methyl-Daspartate receptor(NMDAR)encephalitis,whose treatment requires immunotherapy through nursing interventions.This study aimed to analyze the clinical features and long-term prognosis of pediatric anti-NMDAR encephalitis and to gather nursing experiences of immunotherapy.Methods:Seventeen children diagnosed with anti-NMDAR encephalitis were admitted to the pediatric department.They were subjected to a therapy of intravenous immunoglobulin(IVIG)accompanied with high-dose methylprednisolone(HDMP).Multidisciplinary cooperation and intensive care were used to manage them.The effects of nursing intervention and therapy were repeatedly assessed and analyzed throughout the course of treatment and recovery.Results:None of the patients manifested adverse drug reaction(ADR)during IVIG administration.At the first administration of HDMP,ADRs were promptly and efficiently treated in four patients(24%;i.e.,one case each of hyperglycosemia,hypertension,aggravated symptoms,and gastrointestinal bleed).Two patients underwent rehabilitation,and six patients received hyperbaric oxygenation during hospitalization.Nine patients with indwelling gastric tubes experienced four times of unplanned extubation.Hospital stay ranged from 11 days to 59 days,with the mean duration of 26 days.Discharge evaluation revealed that 16 patients who scored 0e2 on the modified Rankin scale presented obvious remission,and one patient who had a mRS score of 4 exhibited less improvement.The mRS scores of hospitalization,discharge,and six-month follow-up displayed statistically significant differences.Conclusions:Nursing interventions of immunotherapy ensures the security of IVIG administration.Multidisciplinary cooperation promotes remission.Our findings can serve as reference for healthcare teams.展开更多
BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a treatable but frequently misdiagnosed autoimmune disease.Speech dysfunction,as one of the common manifestations of anti-NMDAR encephalitis,is ...BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a treatable but frequently misdiagnosed autoimmune disease.Speech dysfunction,as one of the common manifestations of anti-NMDAR encephalitis,is usually reported as a symptom secondary to psychiatric symptoms or seizures rather than the initial symptom in a paroxysmal form.We report a case of anti-NMDAR encephalitis with paroxysmal speech disorder as a rare initial manifestation,and hope that it will contribute to the literature.CASE SUMMARY A 39-year-old man with anti-NMDAR encephalitis initially presented with paroxysmal nonfluent aphasia and was misdiagnosed with a transient ischemic attack and cerebral infarction successively.The patient subsequently presented with seizures,but no abnormalities were found on brain magnetic resonance imaging or electroencephalogram.Cerebrospinal fluid(CSF)analysis revealed mild pleocytosis and increased protein levels.Anti-NMDAR antibodies in serum and CSF were detected for a conclusive diagnosis.After immunotherapy,the patient made a full recovery.CONCLUSION This case suggests that paroxysmal speech disorder may be the presenting symptom of anti-NMDAR encephalitis in a young patient.展开更多
BACKGROUND A population-based comparative study in United States shows that the prevalence and incidence of autoimmune encephalitis are comparable to those of infectious encephalitis and its detection is increasing ov...BACKGROUND A population-based comparative study in United States shows that the prevalence and incidence of autoimmune encephalitis are comparable to those of infectious encephalitis and its detection is increasing over time.Some patients are complicated with ovarian teratoma.The younger the patient is,the less likely a tumor will be present.CASE SUMMARY This case report describes the successful treatment of anti-N-methyl-D-aspartatereceptor(NMDAR)encephalitis by early laparoscopic ovarian cystectomy and immunotherapy in a 4-year-old female child.And to the best of our knowledge,this detailed case report describes the youngest patient to date with anti-NMDAR encephalitis who underwent laparoscopic ovarian cystectomy.CONCLUSION Although the younger the patient is,the less likely a tumor will be detected,we still emphasize that all patients with suspected or confirmed anti-NMDAR encephalitis should be screened for ovarian tumors if possible.Prompt initiation of immunotherapy and tumor removal are crucial for good outcomes.展开更多
BACKGROUND Anti-N-methyl-D-aspartate receptor encephalitis(NMDARe)is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease,whereas it has been relatively rar...BACKGROUND Anti-N-methyl-D-aspartate receptor encephalitis(NMDARe)is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease,whereas it has been relatively rare.We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease.CASE SUMMARY A 29-year-old man was initially admitted with headache,fever,intermittent abnormal behavior,decreased intelligence,limb twitching and loss of consciousness on July 16,2018.On admission,examination reported no abnormality.During his presentation,he experienced aggravated symptoms,and the reexamination of cranial magnetic resonance imaging(MRI)indicated punctate abnormal signals in the left parietal lobe.External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody(Ab)(-),cerebrospinal fluid NMDAR-Ab(+)1:10 and Epstein-Barr virus capsid antigen antibody Ig G(+).Due to the imaging findings,anti-NMDARe was our primary consideration.The patient was treated with methylprednisolone and gamma globulin pulse therapy,mannitol injection dehydration to reduce intracranial pressure,sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms.The patient was admitted to the hospital for the second time for“abnormal mental behavior and increased limb movements”on December 14,2018.Re-examination of electroencephalography and cranial MRI showed no abnormality.The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive.Considering comprehensive recurrent anti-NMDARe,the patient was treated with propylene-hormone pulse combined with immunosuppressive agents(mycophenolate mofetil),and the symptoms were relieved.The patient was admitted for“hoarseness and double vision”for the third time on August 23,2019.Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe,and synoptophore examination indicated concomitant esotropia.The patient’s visual acuity further decreased,and the reexamination of cranial MRI+enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata,left pons arm,left cerebellum and right midbrain,thalamus.The patient was diagnosed with an accompanying demyelinating disease.Serum antimyelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive.The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome.The patient was successfully treated with methylprednisolone,gamma globulin pulse therapy and rituximab treatment.The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion.CONCLUSION We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.展开更多
We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis(ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and had a good recovery. However, within one month, he developed ...We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis(ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and had a good recovery. However, within one month, he developed severe status epilepticus and decreased level of conscience with new hyperpyrexia and dyspnea, and was admitted to the emergency intensive care unit. Acinetobacter baumanii were found in the sputum culture; and anti-NMDAR antibodies were positive(titer: 1/80) in the cerebrospinal fluid. Repeated immunotherapy was administered with antibacterial agents, and the patient recovered except for mild psychiatric sequelae. This is the first report of ANMDARE that aggravates after acinetobacter baumannii pneumonia. Awareness and knowledge of this disorder should be extended, especially in the emergency medicine community.展开更多
ANTI-N-METHYL-D-ASPARTATE (NMDA) receptorencephalitis is a newly recognized autoimmunedisease. It is predominantly described in youngwomen with a series of symptoms, includingpersonality change, memory loss, seizures,...ANTI-N-METHYL-D-ASPARTATE (NMDA) receptorencephalitis is a newly recognized autoimmunedisease. It is predominantly described in youngwomen with a series of symptoms, includingpersonality change, memory loss, seizures, involuntarymovements, autonomic dysfunction et al.1 It is commonlyassociated with mature ovarian teratomas.2 Since its firstdenomination by Dalmau et al,1 many scientific publicationshave emerged on anti-NMDA receptor encephalitis, butonly a few focused on the anesthetic management ofpatients with this disease.3-5 Herein we reported two caseswith anti-NMDA receptor encephalitis in association withovarian teratoma and discussed the anesthetic managementand the outcomes of these patients.展开更多
BACKGROUND Anti-N-methyl-D-aspartate-receptor(NMDAR)encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations.The pathogenesis of the disease ...BACKGROUND Anti-N-methyl-D-aspartate-receptor(NMDAR)encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations.The pathogenesis of the disease is unclear.Syphilis is an infectious disease caused by Treponema pallidum that can invade the nervous and immune systems and cause systemic symptoms.There are few reports of anti-NMDAR encephalitis with syphilis,and the association between them is unknown;both diseases are related to immune system damage.We report a case of anti-NMDAR encephalitis with syphilis.CASE SUMMARY A 32-year-old man was admitted to our hospital with complaints of cognitive decline,diplopia,and walking instability during the previous 6 mo.He developed dysarthria,difficulty swallowing,and involuntary shaking of his head,neck,and limbs during the month prior to presentation.Cranial magnetic resonance imaging showed symmetrical abnormal signals in the pons,midbrain,and bilateral basal ganglia,and inflammatory demyelination was considered.The diagnosis of syphilis was confirmed based on the syphilis diagnosis test and the syphilis rapid test.He was given anti-syphilis treatment,but the above symptoms gradually worsened.Anti-NMDAR antibody was positive in cerebrospinal fluid but was negative in serum.Due to the cerebrospinal fluid findings,anti-NMDAR encephalitis was a consideration.According to the patient’s weight,he was treated with intravenous methylprednisolone 1 g QD for 5 d,with the dose gradually decreased for 6 mo,and immunoglobulin 25 g QD for 5 d;his symptoms improved after treatment.CONCLUSION This case shows that anti-NMDAR encephalitis may be combined with syphilis,which should be recognized to avoid misdiagnosis and treatment delay.展开更多
Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis has been increasingly recognized in recent years.This condition may be the most common cause of antibody-mediated encephalitis worldwide.The majority of patients a...Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis has been increasingly recognized in recent years.This condition may be the most common cause of antibody-mediated encephalitis worldwide.The majority of patients are young at the time of onset,female,and present with an acute-to-subacute onset of behavioral changes followed by seizure,abnormal movement,autonomic dysfunction,and finally hypoventilation with coma if left untreated.The immunopathogenesis of this disease may be due to antibody-mediated internalization of NMDARs from synapses,which results in the dysfunction of particular brain regions(especially the hippocampus and frontostriatal area).Compared to serum,the cerebrospinal fluid permits the more sensitive detection of anti-NMDAR antibody.Ovarian teratoma may be present in up to 40%of patients but is less frequent in children or late-onset disease(>45 years old).The severity at the time of disease onset and time to appropriate immunotherapy(high-dose steroid plus plasmapheresis or intravenous immunoglobulin)are independent factors that are associated with good outcomes.展开更多
Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,an...Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor.Therefore,while,based on the current knowledge,the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reve rse the disease pathology per se,promoting brainderived neurotrophic factor/tro pomyosin receptor kinase B signaling still has a very high therapeutic relevance.展开更多
Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review...Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with ...Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.展开更多
Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TR...Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC...According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.展开更多
To the Editor:Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a potentially lethal autoimmune disease characterized by prominent psychiatric symptoms and seizures.It usually occurs in young female patients wi...To the Editor:Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a potentially lethal autoimmune disease characterized by prominent psychiatric symptoms and seizures.It usually occurs in young female patients with ovarian teratomas.[1] Here,we describe a severe case of anti-NMDAR encephalitis.The patient was originally misdiagnosed as psychosis and did not improve within the first 4 weeks of first-line immunotherapy.Although she did not continue to receive second-line immunotherapy,the patient still recovered well and had no recurrence or tumor observed during 3 years of follow-up.展开更多
Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor...Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.展开更多
文摘Anti-N-methyl-D-aspartate receptor-associated encephalitis(NMDARE)is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction.The mechanism of pathogenesis remains incompletely understood,but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways.Young adults are most frequently affected;the median age at diagnosis is 21 years.There is a strong female predilection with a female sex predominance of 4:1.NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma.However,NMDARE has also been described in patients with small cell lung cancer,clear cell renal carcinoma,and other benign and malignant neoplasms.Diagnosis is based on correlation of the clinical presentation,electro-encephalography,laboratory studies,and imaging.Computed tomography,positron emission tomography,and magnetic resonance imaging are essential to identify an underlying tumor,exclude clinicopathologic mimics,and predict the likelihood of long-term functional impairment.Nuclear imaging may be of value for prognostication and to assess the response to therapy.Treatment may involve high-dose corticosteroids,intravenous immunoglobulin,and plasma exchange.Herein,we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria,treatment regimens,and proposed pathogenetic mechanisms.
文摘BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a rare autoimmune disorder.The symptoms of anti-NMDAR encephalitis include behavioral problems,speech problems,psychosis,seizures,and memory deficits,among others.However,laryngospasm is rare.We present the case of a patient with anti-NMDAR antibodies and severe laryngospasms.CASE SUMMARY The patient was a 15-year-old female with normal psychomotor development.She was initially admitted to our neurological intensive care unit with seizures.She received anti-epilepsy treatment,and the seizures disappeared.However,2 wk later,she developed behavioral problems and speech impairment.Then,she developed severe laryngospasms,which were treated with intubation and a tracheotomy.Antibodies against the NMDAR were detected in the patient’s cerebrospinal fluid.Therefore,she was diagnosed with anti-NMDAR encephalitis.In addition,she received intravenously administered immunoglobulins,and methylprednisolone was administered.The patient’s symptoms gradually improved,and she was discharged from our hospital.Approximately 9 mo later,the patient could speak sentences,walk independently,and carry out activities of daily living independently.Through our case report,we highlighted laryngospasm as an uncommon presentation in patients with anti-NMDAR encephalitis.CONCLUSION Laryngospasm may be an uncommon clinical manifestation of anti-NMDAR encephalitis.
基金Supported by the Shanghai Municipal Commission of Health and Family Planning,No.2017ZZ02016the Funding from National Key Research and Development Program of China,No.2021YFC2700400+1 种基金the National Natural Science Foundation of China,No.81974454the Shanghai Municipal Key Clinical Specialty,the Clinical Research Plan of SHDC,No.SHDC2020CR6009-002.
文摘BACKGROUND Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a rare but important complication of ovarian teratoma.Between July 2012 and December 2019,six patients with ovarian teratoma-associated anti-NMDAR encephalitis were enrolled in our hospital and their clinical characteristics,treatment,and follow-up were reviewed.We also conducted a systematic literature review of ovarian teratoma related anti-NMDAR encephalitis reports between January 2014 and December 2019.AIM To better understand anti-NMDAR encephalitis through literature review and patients enrolled in our hospital.METHODS The six patients enrolled in the study were those diagnosed with anti-NMDAR encephalitis.Their history,clinical manifestations,and medications were recorded and optimum treatment provided in addition to maintaining a record of the follow-ups.In addition,we also extensively surveyed the literature and provide summarized data from 155 published cases of anti-NMDAR encephalitis from 130 case reports.PubMed and Scopus were the sources of these publications and the time period covered was 6 years ranging from January 2014 through December 2019.RESULTS The six patients enrolled for this study presented with typical symptoms resulting in a diagnosis of ovarian teratoma induced anti-NMDAR encephalitis.Appropriate interventions led to a positive outcome in all the patients,with five of six patients reporting full recovery and the sixth patient recovering with a few deficits.No death was recorded.The literature survey comprising of 155 patients cases across 130 case reports of anti-NMDAR encephalitis clearly indicated an upward trend in the reports/diagnosis in China,particularly in the surveyed time from 2014 through 2019.The majority of patients(150/155)underwent surgical intervention resulting in positive outcome.No treatment intervention was mentioned for one case while the four patients who were not surgically operated succumbed to the disease.CONCLUSION Suspected anti-NMDAR encephalitis should be quickly evaluated for anti-NMDAR antibodies since early diagnosis is important.In case of a tumor,its earliest and complete removal is recommended.Finally,early use of corticosteroids and IgG-depleting strategies(intravenous immunoglobulin or plasma exchange)may improve outcome.
基金We thank the First Affiliated Hospital of the Guangxi Medical University for supplying the case data.We also thank teachers in the pediatric department for their assistance.
文摘Objective:An increasing number of pediatric patients are being diagnosed with anti-N-methyl-Daspartate receptor(NMDAR)encephalitis,whose treatment requires immunotherapy through nursing interventions.This study aimed to analyze the clinical features and long-term prognosis of pediatric anti-NMDAR encephalitis and to gather nursing experiences of immunotherapy.Methods:Seventeen children diagnosed with anti-NMDAR encephalitis were admitted to the pediatric department.They were subjected to a therapy of intravenous immunoglobulin(IVIG)accompanied with high-dose methylprednisolone(HDMP).Multidisciplinary cooperation and intensive care were used to manage them.The effects of nursing intervention and therapy were repeatedly assessed and analyzed throughout the course of treatment and recovery.Results:None of the patients manifested adverse drug reaction(ADR)during IVIG administration.At the first administration of HDMP,ADRs were promptly and efficiently treated in four patients(24%;i.e.,one case each of hyperglycosemia,hypertension,aggravated symptoms,and gastrointestinal bleed).Two patients underwent rehabilitation,and six patients received hyperbaric oxygenation during hospitalization.Nine patients with indwelling gastric tubes experienced four times of unplanned extubation.Hospital stay ranged from 11 days to 59 days,with the mean duration of 26 days.Discharge evaluation revealed that 16 patients who scored 0e2 on the modified Rankin scale presented obvious remission,and one patient who had a mRS score of 4 exhibited less improvement.The mRS scores of hospitalization,discharge,and six-month follow-up displayed statistically significant differences.Conclusions:Nursing interventions of immunotherapy ensures the security of IVIG administration.Multidisciplinary cooperation promotes remission.Our findings can serve as reference for healthcare teams.
文摘BACKGROUND Anti-N-methyl-D-aspartate receptor(anti-NMDAR)encephalitis is a treatable but frequently misdiagnosed autoimmune disease.Speech dysfunction,as one of the common manifestations of anti-NMDAR encephalitis,is usually reported as a symptom secondary to psychiatric symptoms or seizures rather than the initial symptom in a paroxysmal form.We report a case of anti-NMDAR encephalitis with paroxysmal speech disorder as a rare initial manifestation,and hope that it will contribute to the literature.CASE SUMMARY A 39-year-old man with anti-NMDAR encephalitis initially presented with paroxysmal nonfluent aphasia and was misdiagnosed with a transient ischemic attack and cerebral infarction successively.The patient subsequently presented with seizures,but no abnormalities were found on brain magnetic resonance imaging or electroencephalogram.Cerebrospinal fluid(CSF)analysis revealed mild pleocytosis and increased protein levels.Anti-NMDAR antibodies in serum and CSF were detected for a conclusive diagnosis.After immunotherapy,the patient made a full recovery.CONCLUSION This case suggests that paroxysmal speech disorder may be the presenting symptom of anti-NMDAR encephalitis in a young patient.
文摘BACKGROUND A population-based comparative study in United States shows that the prevalence and incidence of autoimmune encephalitis are comparable to those of infectious encephalitis and its detection is increasing over time.Some patients are complicated with ovarian teratoma.The younger the patient is,the less likely a tumor will be present.CASE SUMMARY This case report describes the successful treatment of anti-N-methyl-D-aspartatereceptor(NMDAR)encephalitis by early laparoscopic ovarian cystectomy and immunotherapy in a 4-year-old female child.And to the best of our knowledge,this detailed case report describes the youngest patient to date with anti-NMDAR encephalitis who underwent laparoscopic ovarian cystectomy.CONCLUSION Although the younger the patient is,the less likely a tumor will be detected,we still emphasize that all patients with suspected or confirmed anti-NMDAR encephalitis should be screened for ovarian tumors if possible.Prompt initiation of immunotherapy and tumor removal are crucial for good outcomes.
基金Supported by Health Commission of Shanxi Province Issued"Four Approval"Scientific and Technological Innovation Projects in 2020,No.2020XM38。
文摘BACKGROUND Anti-N-methyl-D-aspartate receptor encephalitis(NMDARe)is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease,whereas it has been relatively rare.We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease.CASE SUMMARY A 29-year-old man was initially admitted with headache,fever,intermittent abnormal behavior,decreased intelligence,limb twitching and loss of consciousness on July 16,2018.On admission,examination reported no abnormality.During his presentation,he experienced aggravated symptoms,and the reexamination of cranial magnetic resonance imaging(MRI)indicated punctate abnormal signals in the left parietal lobe.External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody(Ab)(-),cerebrospinal fluid NMDAR-Ab(+)1:10 and Epstein-Barr virus capsid antigen antibody Ig G(+).Due to the imaging findings,anti-NMDARe was our primary consideration.The patient was treated with methylprednisolone and gamma globulin pulse therapy,mannitol injection dehydration to reduce intracranial pressure,sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms.The patient was admitted to the hospital for the second time for“abnormal mental behavior and increased limb movements”on December 14,2018.Re-examination of electroencephalography and cranial MRI showed no abnormality.The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive.Considering comprehensive recurrent anti-NMDARe,the patient was treated with propylene-hormone pulse combined with immunosuppressive agents(mycophenolate mofetil),and the symptoms were relieved.The patient was admitted for“hoarseness and double vision”for the third time on August 23,2019.Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe,and synoptophore examination indicated concomitant esotropia.The patient’s visual acuity further decreased,and the reexamination of cranial MRI+enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata,left pons arm,left cerebellum and right midbrain,thalamus.The patient was diagnosed with an accompanying demyelinating disease.Serum antimyelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive.The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome.The patient was successfully treated with methylprednisolone,gamma globulin pulse therapy and rituximab treatment.The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion.CONCLUSION We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.
文摘We report an atypical case of anti-N-methyl-D-aspartate receptor encephalitis(ANMDARE). A 27-year-old man diagnosed with ANMDARE received immunotherapy and had a good recovery. However, within one month, he developed severe status epilepticus and decreased level of conscience with new hyperpyrexia and dyspnea, and was admitted to the emergency intensive care unit. Acinetobacter baumanii were found in the sputum culture; and anti-NMDAR antibodies were positive(titer: 1/80) in the cerebrospinal fluid. Repeated immunotherapy was administered with antibacterial agents, and the patient recovered except for mild psychiatric sequelae. This is the first report of ANMDARE that aggravates after acinetobacter baumannii pneumonia. Awareness and knowledge of this disorder should be extended, especially in the emergency medicine community.
文摘ANTI-N-METHYL-D-ASPARTATE (NMDA) receptorencephalitis is a newly recognized autoimmunedisease. It is predominantly described in youngwomen with a series of symptoms, includingpersonality change, memory loss, seizures, involuntarymovements, autonomic dysfunction et al.1 It is commonlyassociated with mature ovarian teratomas.2 Since its firstdenomination by Dalmau et al,1 many scientific publicationshave emerged on anti-NMDA receptor encephalitis, butonly a few focused on the anesthetic management ofpatients with this disease.3-5 Herein we reported two caseswith anti-NMDA receptor encephalitis in association withovarian teratoma and discussed the anesthetic managementand the outcomes of these patients.
基金Supported by the National Natural Science Foundation of China,No.81571057Tianjin Science and Technology Project,No.16ZXMJSY00010
文摘BACKGROUND Anti-N-methyl-D-aspartate-receptor(NMDAR)encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations.The pathogenesis of the disease is unclear.Syphilis is an infectious disease caused by Treponema pallidum that can invade the nervous and immune systems and cause systemic symptoms.There are few reports of anti-NMDAR encephalitis with syphilis,and the association between them is unknown;both diseases are related to immune system damage.We report a case of anti-NMDAR encephalitis with syphilis.CASE SUMMARY A 32-year-old man was admitted to our hospital with complaints of cognitive decline,diplopia,and walking instability during the previous 6 mo.He developed dysarthria,difficulty swallowing,and involuntary shaking of his head,neck,and limbs during the month prior to presentation.Cranial magnetic resonance imaging showed symmetrical abnormal signals in the pons,midbrain,and bilateral basal ganglia,and inflammatory demyelination was considered.The diagnosis of syphilis was confirmed based on the syphilis diagnosis test and the syphilis rapid test.He was given anti-syphilis treatment,but the above symptoms gradually worsened.Anti-NMDAR antibody was positive in cerebrospinal fluid but was negative in serum.Due to the cerebrospinal fluid findings,anti-NMDAR encephalitis was a consideration.According to the patient’s weight,he was treated with intravenous methylprednisolone 1 g QD for 5 d,with the dose gradually decreased for 6 mo,and immunoglobulin 25 g QD for 5 d;his symptoms improved after treatment.CONCLUSION This case shows that anti-NMDAR encephalitis may be combined with syphilis,which should be recognized to avoid misdiagnosis and treatment delay.
文摘Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis has been increasingly recognized in recent years.This condition may be the most common cause of antibody-mediated encephalitis worldwide.The majority of patients are young at the time of onset,female,and present with an acute-to-subacute onset of behavioral changes followed by seizure,abnormal movement,autonomic dysfunction,and finally hypoventilation with coma if left untreated.The immunopathogenesis of this disease may be due to antibody-mediated internalization of NMDARs from synapses,which results in the dysfunction of particular brain regions(especially the hippocampus and frontostriatal area).Compared to serum,the cerebrospinal fluid permits the more sensitive detection of anti-NMDAR antibody.Ovarian teratoma may be present in up to 40%of patients but is less frequent in children or late-onset disease(>45 years old).The severity at the time of disease onset and time to appropriate immunotherapy(high-dose steroid plus plasmapheresis or intravenous immunoglobulin)are independent factors that are associated with good outcomes.
文摘Brain-derived neurotrophic factor signaling via its receptor tro pomyosin receptor kinase B regulates several crucial physiological processes.It has been shown to act in the brain,promoting neuronal survival,growth,and plasticity as well as in the rest of the body where it is involved in regulating for instance aspects of the metabolism.Due to its crucial and very pleiotro pic activity,reduction of brain-derived neurotrophic factor levels and alterations in the brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling have been found to be associated with a wide spectrum of neurological diseases.Howeve r,because of its poor bioavailability and pharmacological properties,brain-derived neurotrophic factor itself has a very low therapeutic value.Moreover,the concomitant binding of exogenous brain-derived neurotrophic factor to the p75 neurotrophin receptor has the potential to elicit several unwanted and deleterious side effects.Therefo re,developing tools and approaches to specifically promote tropomyosin receptor kinase B signaling has become an important goal of translational research.Among the newly developed tools are different categories of tropomyosin receptor kinase B receptor agonist molecules.In this review,we give a comprehensive description of the diffe rent tro pomyosin receptor kinase B receptor agonist drugs developed so far and of the res ults of their application in animal models of several neurological diseases.Moreover,we discuss the main benefits of tropomyosin receptor kinase B receptor agonists,concentrating especially on the new tropomyosin receptor kinase B agonist antibodies.The benefits observed both in vitro and in vivo upon application of tropomyosin receptor kinase B receptor agonist drugs seem to predominantly depend on their general neuroprotective activity and their ability to promote neuronal plasticity.Moreover,tro pomyosin receptor kinase B agonist antibodies have been shown to specifically bind the tropomyosin receptor kinase B receptor and not p75 neurotrophin receptor.Therefore,while,based on the current knowledge,the tropomyosin receptor kinase B receptor agonists do not seem to have the potential to reve rse the disease pathology per se,promoting brainderived neurotrophic factor/tro pomyosin receptor kinase B signaling still has a very high therapeutic relevance.
基金the financial support provided by“Pioneer”and“Leading Goose”R&D Program of Zhejiang(2022C020122022C02078)。
文摘Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.
基金Supported by Xi'an Jiaotong University Medical"Basic-Clinical"Integration Innovation Project,No.YXJLRH2022067Shaanxi Postdoctoral Research Program“Orlistat-loaded Nanoparticles as A Targeted Therapeutical Strategy for The Enhanced Treatment of Liver Cancer”,No.2023BSHYDZZ09.
文摘Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.
基金the Ethics Committee of University Magdeburg(Ethical code:33/0119.03.2001).
文摘Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
文摘According to the latest global cancer statistics,colorectal cancer(CRC)has emerged as the third most prevalent malignant tumor across the globe.In recent decades,the medical field has implemented several levels of CRC screening tests,encompassing fecal tests,endoscopic examinations,radiological examinations and blood tests.Previous studies have shown that leukocyte immunoglobulin-like receptor B2(LILRB2)is involved in inhibiting immune cell function,immune evasion,and promoting tumor progression in acute myeloid leukemia and nonsmall cell lung cancer.However,its interaction with CRC has not been reported yet.Recently,a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand,angiopoietin-like protein 2,are markedly overexpressed in CRC.This overexpression is closely linked to tumor progression and is indicative of a poor prognosis.The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors.However,there is still room for discussion regarding the data processing and analysis in this research.
文摘To the Editor:Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a potentially lethal autoimmune disease characterized by prominent psychiatric symptoms and seizures.It usually occurs in young female patients with ovarian teratomas.[1] Here,we describe a severe case of anti-NMDAR encephalitis.The patient was originally misdiagnosed as psychosis and did not improve within the first 4 weeks of first-line immunotherapy.Although she did not continue to receive second-line immunotherapy,the patient still recovered well and had no recurrence or tumor observed during 3 years of follow-up.
文摘Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.
