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Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.
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BACKGROUND: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth. OBJECTIVE: This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa. METHODS: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice. RESULTS: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12-125I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12-125I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12- 125I/siAPE1 had high efficiency in suppressing PCa tumor growth. CONCLUSION: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa and can provide a theoretical basis for patent applications.
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Antígenos de Superficie , Glutamato Carboxipeptidasa II , Radioisótopos de Yodo , Melatonina , Nanopartículas , Neoplasias de la Próstata , Masculino , Animales , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Humanos , Radioisótopos de Yodo/administración & dosificación , Melatonina/farmacología , Melatonina/administración & dosificación , Línea Celular Tumoral , Nanopartículas/química , Ratones , Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Glutamato Carboxipeptidasa II/metabolismo , Distribución Tisular , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/farmacologíaRESUMEN
Introduction: Baló's concentric sclerosis (BCS) is a rare type of central nervous system demyelinating disorder. Most patients with BCS are treated with corticosteroids, and spontaneous remission has seldom been described. Case presentation: A 46-year-old man presented with a subacute-onset headache and memory loss. Brain magnetic resonance imaging (MRI) revealed multiple onion-shaped ring lesions with mild enhancement in the outermost ring. A brain biopsy revealed significant myelin loss. The diagnosis of BCS was established based on the MRI results and pathological findings. Interestingly, the patient recovered almost completely without immunotherapy, with repeated brain MRI at the 1-year follow-up showing an obvious reduction in the extent of the lesions. Conclusion: Neurologists should improve the recognition of the typical MRI features of BCS to avoid unnecessary biopsies. Although rare, spontaneous remission can be observed in clinical practice.
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Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public.
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Inhibidores de la Bomba de Protones , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéutico , Humanos , Medición de Riesgo , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Reino Unido/epidemiología , Anciano , Estudios Prospectivos , Estados Unidos/epidemiología , Adulto , Medicina de Precisión , Insuficiencia Renal Crónica/inducido químicamente , Isquemia Miocárdica/inducido químicamente , Isquemia Miocárdica/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Infecciones del Sistema Respiratorio/epidemiología , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/epidemiología , Factores de RiesgoRESUMEN
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.
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Neoplasias del Sistema Nervioso Central , Linfoma , Persona de Mediana Edad , Humanos , Medios de Contraste/uso terapéutico , Gadolinio , Inflamación/complicaciones , Esteroides/uso terapéutico , Corticoesteroides/uso terapéutico , Imagen por Resonancia Magnética/métodos , Puente/patología , Neoplasias del Sistema Nervioso Central/patología , Linfoma/complicacionesRESUMEN
The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato , Humanos , Masculino , Adulto Joven , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Convulsiones/complicaciones , SíndromeRESUMEN
The lymphatic vasculature is the natural pathway for the resolution of inflammation, yet the role of pulmonary lymphatic drainage function in sepsis-induced acute respiratory distress syndrome (ARDS) remains poorly characterized. In this study, indocyanine green-near infrared lymphatic living imaging was performed to examine pulmonary lymphatic drainage function in septic mouse models. We found that the pulmonary lymphatic drainage was impaired owing to the damaged lymphatic structure in sepsis-induced ARDS. Moreover, prior lymphatic defects by blocking vascular endothelial growth factor receptor-3 (VEGFR-3) worsened sepsis-induced lymphatic dysfunction and inflammation. Posttreatment with vascular endothelial growth factor-C (Cys156Ser) (VEGF-C156S), a ligand of VEGFR-3, ameliorated lymphatic drainage by rejuvenating lymphatics to reduce the pulmonary edema and promote draining of pulmonary macrophages and neutrophils to pretracheal lymph nodes. Meanwhile, VEGF-C156S posttreatment reversed sepsis-inhibited CC chemokine ligand 21 (CCL21), which colocalizes with pulmonary lymphatic vessels. Furthermore, the advantages of VEGF-C156S on the drainage of inflammatory cells and edema fluid were abolished by blocking VEGFR-3 or CCL21. These results suggest that efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. Our findings offer a therapeutic approach to sepsis-induced ARDS by promoting lymphatic drainage function.
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Vasos Linfáticos , Síndrome de Dificultad Respiratoria , Sepsis , Ratones , Animales , Factor C de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ligandos , Vasos Linfáticos/patología , Inflamación/metabolismo , Síndrome de Dificultad Respiratoria/patología , Sepsis/metabolismoRESUMEN
AIM: To investigate the pharmacokinetic properties of the main active components of Dalitong extract in SD rats after oral administration using UPLC-MS / MS. METHODS: An UPLC-MS / MS method was established to simultaneously detect tetrahydropalmatine, nobiletin and costunolide in the plasma and tissues of SD rats. The method was applied to investigate the pharmacokinetic characteristics and tissue distribution. RESULTS: After a single oral administration, the three active components were rapidly absorbed into the body, with a peak concentration (Cmax) of (13.73 ± 7.50), (27.01 ± 17.69) and (6.73 ± 29.94) ng / mL for tetrahydropalmatine, nobiletin, and costunolide, respectively. The time to reach the peak concentration (Tmax) was (1.40 ± 0.93), (0.63 ± 0.28) and (2.38 ± 8.81) h, respectively. The area under the curve (AUC) was (80.43±40.03), (41.30±28.69) and (303.90 ± 136.69) ng · h · mL
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Objective @#To explore the association between mammalian sterile 20-like kinase 1(MST1)gene poly- morphism and haplotype and the risk of colorectal cancer,rectal cancer,and colon cancer in the Han population in Baotou area by case-control association study@*Methods @#A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination population were collected,and 2 ml of peripheral blood was taken for subsequent gene genotyping.Single nucleotide polymorphisms(SNPs)of MSTI gene were screened according to the genetic polymorphism data of Chinese Han population provided by the National Center for Biotechnology Information-Haplotype Mapping database.Gene genotyping was performed by Taqman method.Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer,colon cancer,and rectal cancer under codominant,dominant,overdominant,and recessive genetic models.@*Results @#Four SNPs of MSTI gene were screened,namely rs8000,rs2234197,rs2267853,and rs6073629.Among them,SNP rs2234197 was associated with the risk of rectal cancer.Compared with the GG+AA genotype,the AG genotype could reduce the risk of rectal cancer, OR[95%confidence interval(CI)]=0.657(0.442-0.976).SNP rs8000 was associated with the risk of colon cancer.Compared with the TT+GT genotype,theGG genotype could reduce the risk of colon cancer [OR(95%CI)=0.425(0.182, -0.992)].@*Conclusion @#MSTI gene SNP rs2234197 AG genotype and SNP rs8000 GG genotype may be protective factors for rectal cancer and colon cancer,respectively.
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BACKGROUND: Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. METHODS: TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as 'worst chest pain over the last week' equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. DISCUSSION: Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. TRIAL REGISTRATION: NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856 . First patient recruited 8 January 2019.
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Dolor Agudo , Analgesia Epidural , Dolor Crónico , Bloqueo Nervioso , Adulto , Humanos , Adolescente , Toracotomía/efectos adversos , Dolor Crónico/diagnóstico , Dolor Crónico/etiología , Dolor Crónico/prevención & control , Analgesia Epidural/efectos adversos , Analgesia Epidural/métodos , Dolor Agudo/diagnóstico , Dolor Agudo/etiología , Dolor Agudo/prevención & control , Calidad de Vida , Bloqueo Nervioso/efectos adversos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.
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The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.
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INTRODUCTION: The aim of this retrospective cohort study was to evaluate the clinical outcomes and identify the prognostic factors of endodontic microsurgery based on cone-beam computed tomographic (CBCT) scans. METHODS: Patients who underwent endodontic microsurgery in teeth with asymptomatic apical periodontitis were included. The clinical outcomes were determined based on clinical and radiographic examinations after surgery 12-48 months. Radiographic healing was assessed on CBCT images by using the modified PENN 3-dimensional criteria and classified into 4 categories: complete, limited, uncertain, and unsatisfactory healing. Multivariate logistic regression was performed to detect outcome risk factors. RESULTS: Of the 204 teeth in 173 invited patients, 148 teeth of 126 patients were examined at review. On CBCT images, 88 teeth (59.5%) showed complete healing, and 42 (28.4%) teeth showed limited healing. All these 130 teeth were asymptomatic and achieved a clinical success rate of 87.8%. Uncertain healing was observed in 9 teeth, one of which was symptomatic. The remaining 9 teeth were unsatisfactory healing on CBCT scans, including 6 teeth with clinical symptoms and 3 free. Lesion type and root-end filling quality were significant outcome predictors (P < .05). The risk of treatment failure for teeth with combined endodontic-periodontal lesions was 8.6 times higher than that for teeth with isolated endodontic lesions. Adequate root-end filling quality improved the probability of success by 5.3 times. CONCLUSIONS: Based on CBCT data, an adequate performed endodontic microsurgery could have predictable success in teeth without periodontal involvement.
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OBJECTIVES: Talaromyces marneffei is an emerging pathogen, and the number of infections in HIV-negative individuals is rapidly increasing. Nevertheless, there is no sufficient comprehensive report on this issue, and awareness needs to be raised among clinicians. METHODS: We analyzed the differences in the clinical data of patients who are HIV-negative and HIV-positive with Talaromyces marneffei infection (TMI) from 2018 to 2022. RESULTS: A total of 848 patients were included, among whom 104 were HIV-negative. The obvious differences between the HIV-positive and HIV-negative groups were as follows: (i) the patients who are HIV-negative were older and more likely to exhibit cough and rash, (ii) the time in days from symptom onset to diagnosis among patients who are HIV-negative was longer, (iii) the laboratory findings and radiological presentations seemed more severe in patients who are HIV-negative, (iv) differences were observed regarding the underlying conditions and co-infection pathogens, and correlation analysis showed that correlations existed for many indicators, (v) and persistent infection was more likely to occur in patients who are HIV-negative. CONCLUSION: TMI in patients who are HIV-negative differs from that in patients who are HIV-positive in many aspects, and more investigations are needed. Clinicians should be more aware of TMI in patients who are HIV-negative.
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Infecciones por VIH , Micosis , Talaromyces , Humanos , Micosis/complicaciones , Micosis/diagnóstico , Micosis/microbiología , Micosis/patología , Estudios Retrospectivos , Infecciones por VIH/complicaciones , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
On March 23, 2022, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have highly expressed prostate-specific membrane antigen (PSMA) and have at least one metastatic lesion. It is the first FDA-approved targeted radioligand therapy for eligible men with PSMA-positive mCRPC. Lutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation, resulting in DNA damage and cell death. PSMA is overexpressed in cancer cells while being lowly expressed in normal tissues, which makes it an ideal theranostic target. As precision medicine advances, this is a thrilling turning point for highly individualized treatments. This review aims to summarize the pharmacology and clinical studies of the novel drug lutetium Lu 177 vipivotide tetraxetan for the treatment of mCRPC, emphasizing its mechanism of action, pharmacokinetics and safety.
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Lutecio , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Lutecio/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Antígeno Prostático Específico/uso terapéutico , Resultado del TratamientoRESUMEN
Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.
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Enfermedades Autoinmunes del Sistema Nervioso , Hospitalización , Masculino , Humanos , Estudios Retrospectivos , PronósticoRESUMEN
Objective:To construct a diabetic foot classification prediction model based on radiomics features of fundus photographs.Methods:A total of 2 035 fundus photographs of patients with type 2 diabetes diagnosed at Nanfang Hospital between December 2011 and December 2018 were retrospectively collected [282 photographs from patients with diabetic foot(DF), and 1 753 from patients with diabetes mellitus(DM)]. All fundus photographs were randomly divided into a training set(1 424 photos) and a test set(611 photos) using a computer generated random number at 7∶3. After pre-processing the fundus photographs, a total of 4 128 texture features based on the gray matrix were extracted by the Radiomic toolkit, and 11 339 other features were extracted using the ToolboxDESC toolkit. The LASSO algorithm was used to select the 30 features most relevant to DF, and then the Bootstrap + 0.632 self-sampling method was used to further select the 7 best combinations. Logistic regression analysis was used to obtain the regression coefficients and establish the final diabetic foot classification prediction model. ROC curve was drawn, and AUC, sensitivity, specificity, and accuracy of the training and test sets were calculated to verify its prediction performance. Results:We screened 7 fundus radiomics markers for diabetic foot patients, and based on this established a DF/DM classification prediction model. The AUC, sensitivity, specificity, and accuracy of the model were 0.958 6, 0.984 0, 0.920 0, and 0.928 0 in the training set, and 0.927 1, 0.988 9, 0.881 0, and 0.896 9 in the test set, respectively.Conclusion:In this study, seven DF fundus markers were screened using radiomics technology. Based on this, a highly accurate and easy-to-use DF/DM classification model was constructed. This technology has the potential to increase the efficiency of DF screening programs.
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Objective: To explore the present situation and epidemiological characteristics of pesticide poisoning in Chengdu City from 2012 to 2021, and to provide scientific evidence for further prevention and control. Methods: In January 2022, the pesticide poisoning report cards of Chengdu City from 2012 to 2021 were collected from the China Disease Control and Prevention Information System. The data of the report card was reorganized and the distribution characteristics of pesticide poisoning such as time, region, gender, age and pesticide types were analyzed. Results: 14326 cases of pesticide poisoning were reported in Chengdu City from 2012 to 2021, 651 deaths, and the fatality rate was 4.54%. The cases of productive pesticide poisoning and unproductive pesticide poisoning were 504 and 13822, respectively. The fatality rates of productive and unproductive pesticide poisoning were 1.39% and 4.66%, which were significant different (χ(2)=11.99, P=0.001). The highest reported cases of pesticide poisoning was in 2013 (1779) and the lowest in 2021 (1047). The number of reported cases showed a downward trend year by year (t=-12.30, P<0.001), and the fatality rates also showed a downward trend year by year (χ(2)(trend)=25.48, P<0.001). The fluctuation range of unproductive pesticide poisoning cases in each month of the year was small, and the productive pesticide poisoning mainly occurred from May to August. The regions with the largest number of reported poisoning cases were Pengzhou (1620), Jianyang (1393), Jintang (1266) and Qionglai (1158). The high incidence of poisoning was among 25-54 years old (50.21%, 7193/14326). The fatality rate in the age group 75-96 years old was the highest (8.98%, 95/1058), and the fatality rates increased gradually with age (χ(2)(trend)=186.03, P<0.001). The pesticides causing poisoning were mainly insecticide (43.86%, 6284/14326) and herbicides (35.75%, 5121/14326). Herbicides paraquat had the highest fatality rate (9.54%, 286/2998) . Conclusion: Pesticide poisoning in Chengdu City is mainly unproductive poisoning. Health education should be carried out for key areas and people, and the control of highly toxic pesticides such as insecticide and herbicides should be strengthened.
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Humanos , Anciano , Anciano de 80 o más Años , Adulto , Persona de Mediana Edad , Insecticidas , Plaguicidas , Herbicidas , Paraquat , Ciudades , Intoxicación/epidemiologíaRESUMEN
Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.