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1.
RSC Adv ; 14(40): 29606-29623, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39297039

RESUMEN

The treatment of diabetic wounds remains a formidable clinical challenge worldwide. Because of persistent inflammatory reaction, excessive oxidative stress, cell dysfunction, poor blood microcirculation and other microvascular complications, diabetic wounds often fall into inflammatory circulation and are difficult to heal, making patients confront the risk of amputation. In this study, silver complex nanoparticles with Resina Draconis extract and Rhodiola rosea L. extract were loaded in situ onto thermoplastic polyurethane nanofibers to develop a multifunctional electrospun nanofiber wound dressing with excellent mechanical properties, superior water absorption and breathability, good coagulation promoting activity, strong antibacterial performance and antioxidant properties. This wound dressing could effectively enhance the migration and proliferation of fibroblasts, reduce the increased thickness of regenerated epidermis caused by diabetes, and the high expression and high lipid peroxidation levels of IL-1 ß, IL-6, TNF α, iNOS and MMP-9, and raise the low expression of VEGF, which shows great potential to accelerate the wound healing of diabetic mouse models. The wound healing rate reached about 87.92%, close to the non-diabetic group. Our findings suggest a breakthrough in diabetic wound care, offering a viable solution to a long-standing medical shackle.

2.
Cancer Biomark ; 41(1): 25-40, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39269824

RESUMEN

BACKGROUND: Chronic atrophy gastritis (CAG) is a high-risk pre-cancerous lesion for gastric cancer (GC). The early and accurate detection and discrimination of CAG from benign forms of gastritis (e.g. chronic superficial gastritis, CSG) is critical for optimal management of GC. However, accurate non-invasive methods for the diagnosis of CAG are currently lacking. Cytokines cause inflammation and drive cancer transformation in GC, but their utility as a diagnostic for CAG is poorly characterized. METHODS: Blood samples were collected, and 40 cytokines were quantified using a multiplexed immunoassay from 247 patients undergoing screening via endoscopy. Patients were divided into discovery and validation sets. Each cytokine importance was ranked using the feature selection algorithm Boruta. The cytokines with the highest feature importance were selected for machine learning (ML), using the LightGBM algorithm. RESULTS: Five serum cytokines (IL-10, TNF-α, Eotaxin, IP-10 and SDF-1a) that could discriminate between CAG and CSG patients were identified and used for predictive model construction. This model was robust and could identify CAG patients with high performance (AUC = 0.88, Accuracy = 0.78). This compared favorably to the conventional approach using the PGI/PGII ratio (AUC = 0.59). CONCLUSION: Using state-of-the-art ML and a blood-based immunoassay, we developed an improved non-invasive screening method for the detection of precancerous GC lesions. FUNDING: Supported in part by grants from: Jiangsu Science and Technology Project (no. BK20211039); Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (BJ2023008); Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021010), Wuxi Science and Technology Bureau Project (no. N20201004); Scientific Research Program of Wuxi Health Commission (Z202208, J202104).


Asunto(s)
Citocinas , Gastritis Atrófica , Aprendizaje Automático , Humanos , Femenino , Masculino , Citocinas/sangre , Persona de Mediana Edad , Gastritis Atrófica/sangre , Gastritis Atrófica/diagnóstico , Neoplasias Gástricas/sangre , Neoplasias Gástricas/diagnóstico , Anciano , Adulto , Detección Precoz del Cáncer/métodos , Enfermedad Crónica
3.
J Gastrointest Oncol ; 15(4): 1399-1408, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39279941

RESUMEN

Background: Chemotherapy with SOX (S-1 and oxaliplatin) regimen showed good efficacy and a favorable safety profile in advanced gastric cancer. Anti-programmed cell death protein 1 (PD-1) antibody camrelizumab also demonstrated antitumor activity in this setting in a phase I study. However, the efficacy and safety of camrelizumab plus SOX for advanced gastric cancer have not been investigated. Thus, this study aimed to address this objective. Methods: This phase II study evaluated the efficacy and safety of camrelizumab plus SOX in previously untreated advanced gastric cancer. Patients received camrelizumab (200 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, death, or intolerable toxicity. Camrelizumab was prescribed for up to a year. The primary endpoint was progression-free survival (PFS). The second endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 25 patients were enrolled and received at least 1 dose of study drug. The median PFS was 7.4 months [95% confidence interval (CI): 5.6-16.4]. The median OS was 20.2 months (95% CI: 10.5-29.9); ORR was 36% (95% CI: 18.0-57.5%); DCR was 92% (95% CI: 74.0-99.0%). Among the 25 patients, 22 (88%) experienced any-grade adverse events (AEs), and 7 (28%) patients experienced grade ≥3 AEs. Conclusions: Camrelizumab plus SOX showed promising efficacy and an acceptable safety profile as the first-line treatment for advanced gastric cancer.

4.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1553-1563, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39235013

RESUMEN

Aiming for clarifying the potential distribution characteristics of canopy rainfall partitioning of the loess area, we explored the process of rainfall partitioning across eight typical forest stands (Pinus tabuliformis forest, Robinia pseudoacacia forest, Platycladus orientalis forest, mixed forest of Robinia pseudoacacia-Pinus tabuliformis, mixed forest of Platycladus orientalis-Robinia pseudoacacia, Quercus wutaishanica forest, Populus davidiana forest, mixed forest of Quercus wutaishanica-Populus davidiana), and used boosted regression trees (BRT) to quantify the relative influences of stand structures and meteorological environment factors. We established multiple regression relationships according to the most influential factors extracted by BRT, and applied to the dataset of mining to verify the performance of the BRT-derived predictive model. The results showed that the percentages of throughfall (TF), stemflow (SF), and canopy interception (Ic) in total precipitation were 24.5%-95.1%, 0-13.6%, and 0.7%-55.7% among eight typical forest stands, respectively. For the individual rainfall threshold of TF, coniferous forest (3.06±1.21 mm) was significantly higher than broad-leaved forest (1.97±0.52 mm), but there was no significant difference between coniferous forest and broad-leaved mixed forest (3.01±0.98 mm). There was no significant difference in the individual rainfall threshold of SF among different composition stands. BRT analysis showed that stand structure factors accounted for a relatively small proportion for TF and SF, respectively. By contrast, stand structure factors dominated the Ic. Rainfall was the most important factor in determining TF and SF. Tree height was the most important factor in determining Ic, followed by rainfall, canopy area, diameter at breast height, and stand density. Compared with the general linear function and the power function, the prediction effect of BRT prediction model constructed here on TF and SF had been further improved, and the prediction of canopy interception still needed to explore. In conclusion, the BRT model could better quantitatively evaluate the effects of stand structure and meteorological environmental factors on rainfall partitioning components, and the performance of the BRT predictive model could satisfy and lay the foundation for the optimization strategy for stand configuration.


Asunto(s)
Bosques , Lluvia , Árboles , China , Árboles/crecimiento & desarrollo , Árboles/clasificación , Ecosistema , Quercus/crecimiento & desarrollo , Robinia/crecimiento & desarrollo , Altitud , Populus/crecimiento & desarrollo
5.
Ann Med ; 56(1): 2363940, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39212199

RESUMEN

BACKGROUND: Previous research has strongly supported the utility of spaced learning in enhancing memory, but its effectiveness in complex surgical procedures has largely been unexplored. The main objective of this study was to evaluate whether, in comparison to concentrated learning, spaced learning improves the short-term acquisition and long-term retention of cosmetic suturing skills as outcomes of surgical resident training courses. METHODS: This randomized controlled trial was conducted from February 2023 to June 2023. Surgical residents were recruited from a teaching hospital in Guangzhou, China. The participants were randomly assigned at a 1:1 ratio to either the spaced training group (40 min of training followed by a 20-minute break) or the concentrated training group (3 h of continuous training), in which they received one-on-one training for cosmetic suturing skills. The short-term acquisition and long-term retention outcomes were evaluated by three independent raters using an objective scoring scale to assess the participants' cosmetic suturing skills before the training (pretraining test), within one hour after the training (posttraining test), and three months after the completion of the training (follow-up test). The score for each participant was calculated as the average of three independent scores. RESULTS: The study included 23 surgical residents, 12 in the spaced training group and 11 in the concentrated training group. The pretraining test revealed no significant difference between the groups. However, in the post-training test, the spaced training group achieved a significantly higher total score than did the concentrated training group (74.06 ± 5.87 vs. 63.43 ± 10.73, p = 0.0070). Specifically, the suture technique scores were 28.46 ± 1.78 and 22.85 ± 3.75, respectively, which were significantly different (p = 0.0002). During the long-term follow-up test, the spaced training group consistently outperformed the concentrated training group by having significantly higher total (75.60 ± 4.78 vs. 60.68 ± 10.40, p = 0.0001), suture quality (32.26 ± 4.01 vs. 26.23 ± 4.16, p = 0.0019), suture technique (28.68 ± 2.63 vs. 22.18 ± 3.94, p = 0.0001), and suturing time scores (14.67 ± 1.15 vs. 12.27 ± 6.07, p = 0.0460). CONCLUSIONS: Incorporating the principles of spaced learning into the instructional process of obtaining cosmetic suture skills for surgical residents not only significantly enhances short-term skill improvement but also contributes to the long-term retention of training outcomes.


During the post-training test conducted to evaluate short-term impacts, the spaced training group showed notably elevated overall scores, particularly in the domain of suture technique, compared to the concentrated training group.In the long-term follow-up test, the spaced training group achieved significantly higher scores on the overall test, suture quality, suture technique, and suturing time than the concentrated training group.By incorporating the principles of spaced learning into the instructional process of cosmetic suture skills for surgical residents, not only does it significantly enhance short-term skill improvement, but it also contributes to the long-term retention of training outcomes.


Asunto(s)
Competencia Clínica , Internado y Residencia , Técnicas de Sutura , Humanos , Técnicas de Sutura/educación , Internado y Residencia/métodos , Masculino , Femenino , Adulto , China , Aprendizaje
6.
Acta Trop ; 259: 107372, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39214234

RESUMEN

Schistosomiasis is caused by Schistosoma infection and affects more than 200 million people worldwide. A large number of eggs produced by adult Schistosoma play central the role in host pathology and subsequent disease dissemination. However, the underlying mechanisms of egg production in Schistosoma still need to be further elucidated. Previously, we found that miR-31 was highly enriched in the female reproductive organs of Schistosoma japonicum (S. japonicum), which was shown to be associated with ovarian development. In the present study, we analyzed the potential targets of miR-31 including mRNA and long noncoding RNAs (lncRNAs) in S. japonicum by RNA seq combined with bioinformatics. Then, six putative targets of miR-31 including three mRNAs such as EWB00_000918, EWB00_004242, and EWB00_009323 and three lncRNAs such as LncSJG_010465, LncSJG_015374 and LncSJG_013128 were further analyzed their expressions in the parasites treated with miR-31 inhibitor by qPCR to confirm their potential regulations. Whole mount in suit hybridization (WISH) analysis of some miR-31 targets were carried out to determine their colocalizations with miR-31. Furthermore, we selected EWB00_009323, which is an eggshell synthetic protein and also a target of miR-31, to inhibit its functions by small interfering RNA. The results indicated that inhibition of EB00_009323 led to decreased oviposition and defective ovarian morphology. Overall, the potential targets of miR-31 including mRNA and lncRNAs were identified in female S. japonicum and the results indicated that miR-31 coordinates with its targets, at least EWB00_009323, play an important role in ovarian development and egg production.


Asunto(s)
MicroARNs , Schistosoma japonicum , Animales , Schistosoma japonicum/genética , Schistosoma japonicum/crecimiento & desarrollo , Femenino , MicroARNs/genética , Ratones , Óvulo/crecimiento & desarrollo , ARN Largo no Codificante/genética , Esquistosomiasis Japónica/parasitología , ARN Mensajero/genética , Oviposición
7.
Small ; : e2405009, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106215

RESUMEN

The efficient utilization of the metallic Zn in rechargeable aqueous Zn-ion batteries (RAZBs) struggle to suffer from parasitic Zn dendrite formation, hydrogen evolution reactions as well as severe interfacial degradation at high areal capacity loadings. This study thus proposes to employ the modified crown ether as an aqueous electrolyte additive to regulate the Zn2+ desolvation kinetic and facilitates the horizontally oriented (002) deposition of Zn, extending the lifespan of both the symmetric cell and full cell models. Specifically, zincophilic cyano and hydrophobic selenium atoms are incorporated into the crown ether supramolecule to enhance Zn2+ coordination and desolvation capability. The addition of 4-cyanobenzo-21-crown-7-selenium at a low concentration of 0.5 wt.% effectively mitigates hydrogen evolution and Zn corrosion caused by water, promoting the oriented deposition of Zn2+. The Zn||V2O5 full cell prototype, assembled with the areal capacity loadings of 2 mAh cm-2 and N/P ratio of 2.95, exhibits negligible capacity fading at 2.0A g-1 for 300 cycles, highlighting the commercial feasibility of supramolecular macrocycles additive for practical RAZBs applications.

8.
Clin Lab ; 70(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39193969

RESUMEN

BACKGROUND: Tuberculosis often presents on imaging in the form of a solitary nodule, sometimes accompanied by elevated CEA, which is clinically difficult to differentiate from lung cancer and prone to misdiagnosis. METHODS: Lung tissue taken by lung biopsy and sent for NGS and Xpert MTB/RIF finally led to the definitive diag-nosis of nodular foci in the upper lobe of the left lung caused by tuberculosis. RESULTS: Enhanced CT of the chest showed nodular foci in the upper lobe of the left lung. Initially the nodules were thought to be malignant, but after a series of tests, were finally confirmed to be tuberculosis. CONCLUSIONS: In patients with lung disease, when chest imaging reveals a space-occupying lesion accompanied by an elevated CEA level, a comprehensive analysis of the type of lung disease, the patient's age, and comorbidities should be performed before final diagnosis to avoid misdiagnosis and delay in appropriate treatment.


Asunto(s)
Antígeno Carcinoembrionario , Errores Diagnósticos , Neoplasias Pulmonares , Humanos , Antígeno Carcinoembrionario/sangre , Neoplasias Pulmonares/diagnóstico , Masculino , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/sangre , Diagnóstico Diferencial , Tomografía Computarizada por Rayos X , Persona de Mediana Edad , Pulmón/patología , Pulmón/diagnóstico por imagen , Femenino
9.
Clin Lab ; 70(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39193957

RESUMEN

BACKGROUND: As an opportunistic pathogenic fungus, Schizophyllum has been rarely reported to infect humans. By reporting a case of definite diagnosis of Schizophyllum infection, we aim to improve clinicians' understanding of this bacterium. METHODS: By reporting a case with cough and sputum as the main manifestations, after empirical antiinfective chest CT suggesting a more progressive inflammatory lesion and a mass-like lesion in the paratracheal area of the main airways, a diagnosis of Schizophyllum infection was finally made by bronchoscopy with the delivery of metagenomic next-generation sequencing (mNGS). RESULTS: The patient was finally diagnosed with rare Schizophyllum infection. After antifungal treatment, the symptoms improved, and the patient was discharged. CONCLUSIONS: Although Schizophyllum is a rare fungal infection, it should be taken seriously in patients with diabetes or who are immunocompromised. At the same time, mNGS plays a key role in the detection of rare and emerging pathogens, which is worthy of clinical interest.


Asunto(s)
Antifúngicos , Schizophyllum , Humanos , Schizophyllum/aislamiento & purificación , Schizophyllum/genética , Antifúngicos/uso terapéutico , Eosinofilia/diagnóstico , Eosinofilia/microbiología , Masculino , Broncoscopía , Secuenciación de Nucleótidos de Alto Rendimiento , Tomografía Computarizada por Rayos X , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Persona de Mediana Edad , Micosis/diagnóstico , Micosis/microbiología , Micosis/tratamiento farmacológico , Micosis/complicaciones
10.
Clin Lab ; 70(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39193952

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV) is a single-stranded RNA virus that commonly causes symptoms of upper respiratory tract infections in humans, with a clear seasonal trend. However, in immunocompromised and elderly patients, RSV infections still result in high rates of hospitalization and even risk of death. METHODS: We report a case of RSV infection in an adult with immunodeficiency, which initially showed only mild symptoms of upper respiratory tract infection, which did not improve after receiving empirical anti-infective treatment, and the foci of infection in the lungs continued to expand, which led to the aggravation of the disease. The diagnosis of RSV infection was finally confirmed by electron bronchoscopy and pathogenetic examination of the bronchoalveolar lavage fluid. The patient was given intravenous ribavirin treatment for one week. After one week of intravenous ribavirin treatment, the patient's symptoms improved significantly. A repeat chest CT suggested that the lung lesions were smaller than before. In order to improve clinicians' awareness of this disease, we jointly conducted a literature analysis. RESULTS: The final diagnosis of RSV was made by analyzing the patient's history, symptoms, and signs and performing relevant examinations. CONCLUSIONS: For patients with poor results of empirical application of antibiotics, electronic bronchoscopy and pathogenetic examination should be carried out at an early stage to clarify the nature of the lesions and to avoid rapid deterioration of the condition leading to life-threatening conditions in the patients. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis, and appropriate treatment should be given at an early stage.


Asunto(s)
Antivirales , Infecciones por Virus Sincitial Respiratorio , Ribavirina , Humanos , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Ribavirina/uso terapéutico , Ribavirina/administración & dosificación , Masculino , Líquido del Lavado Bronquioalveolar/virología , Huésped Inmunocomprometido , Broncoscopía , Adulto , Tomografía Computarizada por Rayos X , Persona de Mediana Edad , Resultado del Tratamiento
11.
Clin Lab ; 70(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39193971

RESUMEN

BACKGROUND: Thymomas are thymic epithelial-derived, most common primary anterior mediastinal masses. Non-tuberculous mycobacteria (NTM) are species that do not cause leprosy and belong to species outside the Mycobacterium tuberculosis complex. METHODS: With the clinical application of targeted next-generation sequencing (tNGS), we promptly confirmed a case of NTM infection combined with NTM infection after thymoma surgery, and we performed a joint literature analysis of the two diseases to improve clinicians' understanding and recognition of lung infections after thymoma surgery. RESULTS: Chest CT of both lungs showed multiple hyperdense shadows. Sputum bacterial culture and characterization detected Neisseria Dryad and Streptococcus Grass Green. The presence of Mycobacterium abscessus infection was confirmed by alveolar lavage fluid sent for second-generation macro gene sequencing. CONCLUSIONS: The body's immune function decreases after thymoma surgery. When empirical anti-infection treatment for recurrent pneumonia in the lungs is ineffective, we should be alerted to the possibility of the presence of pulmonary non-tuberculous mycobacterial infection, and next-generation sequencing should be performed promptly to arrive quickly at a diagnosis.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Timoma , Humanos , Timoma/cirugía , Timoma/complicaciones , Timoma/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/etiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Secuenciación de Nucleótidos de Alto Rendimiento , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/microbiología , Neoplasias del Timo/cirugía , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Masculino , Persona de Mediana Edad , Mycobacterium abscessus/aislamiento & purificación , Femenino , Tomografía Computarizada por Rayos X
12.
Clin Lab ; 70(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39193972

RESUMEN

BACKGROUND: Pulmonary mucormycosis is most common in patients with hematologic malignancies and transplant recipients. This article describes a case of mucormycosis in the lungs secondary to a hematologic disorder with suspected lung cancer. METHODS: Rhizopus (Rhizopus microspores) was detected by blood NGS and bronchoalveolar lavage fluid NGS, and pulmonary mucormycosis was confirmed. RESULTS: Secondary to hematologic disease, pulmonary pneumonia, mycosis, and symptoms improved after comprehensive treatment. CONCLUSIONS: Clinical data and radiologic knowledge are combined to diagnose invasive pulmonary mycoses; early empirical medicine is very important.


Asunto(s)
Enfermedades Pulmonares Fúngicas , Mucormicosis , Rhizopus , Humanos , Mucormicosis/diagnóstico , Mucormicosis/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/complicaciones , Rhizopus/aislamiento & purificación , Masculino , Líquido del Lavado Bronquioalveolar/microbiología , Antifúngicos/uso terapéutico , Persona de Mediana Edad , Enfermedades Hematológicas/complicaciones , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/microbiología , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/microbiología , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/complicaciones
13.
Front Pharmacol ; 15: 1430451, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086386

RESUMEN

Membranous nephropathy (MN) continues to be a leading cause of nephrotic syndrome in non-diabetic adults. As a unique subtype in the serology-based classification of MN, thrombospondin type 1 domain containing 7A (THSD7A)-associated MN has attracted increasing interest, because, unlike other autoantigens, THSD7A is also expressed in preclinical species, facilitating the study of its role in MN. A heterologous mouse model of THSD7A-associated MN was previously established using a proprietary in-house antibody that was unfortunately not available to the research community. Here, we developed a mouse model of THSD7A-associated MN by administering a commercially available antibody targeting the most N-terminal part of THSD7A. Our model was characterized by heavy proteinuria and pathological features of human MN without sex differences. Complement depletion with cobra venom factor only partially attenuated proteinuria and glomerular injury in this model, entailing that complement-independent pathomechanisms also contribute. Consistently, in vitro in primary podocytes, exposure to the anti-THSD7A antibody caused evident podocytopathic changes, including disruption of actin cytoskeleton integrity, podocyte hypermobility, oxidative stress, and apoptotic cell death. These signs of podocytopathy were preserved, albeit to a lesser extent, after complement inactivation, indicating autonomous podocyte injury. Furthermore, as the first FDA-approved treatment for primary MN, adrenocorticotropic hormone therapy with repository corticotropin injection (Purified Cortrophin Gel®) appeared to be beneficial and significantly attenuated proteinuria and glomerular injury, suggesting that this model may be useful for developing novel treatments or understanding the pathogenesis of MN. Collectively, our model, based on the use of a commercially available anti-THSD7A antibody, will be an important tool for MN research.

14.
Neural Netw ; 180: 106638, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39208464

RESUMEN

Identifying anomalies in multi-dimensional sequential data is crucial for ensuring optimal performance across various domains and in large-scale systems. Traditional contrastive methods utilize feature similarity between different features extracted from multidimensional raw inputs as an indicator of anomaly severity. However, the complex objective functions and meticulously designed modules of these methods often lead to efficiency issues and a lack of interpretability. Our study introduces a structural framework called SimDetector, which is a Local-Global Multi-Scale Similarity Contrast network. Specifically, the restructured and enhanced GRU module extracts more generalized local features, including long-term cyclical trends. The multi-scale sparse attention module efficiently extracts multi-scale global features with pattern information. Additionally, we modified the KL divergence to suit the characteristics of time series anomaly detection, proposing a symmetric absolute KL divergence that focuses more on overall distribution differences. The proposed method achieves results that surpass or approach the State-of-the-Art (SOTA) on multiple real-world datasets and synthetic datasets, while also significantly reducing Multiply-Accumulate Operations (MACs) and memory usage.

15.
bioRxiv ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39211124

RESUMEN

Genome-wide association studies have identified SH2B3 as an important non-MHC gene for islet autoimmunity and type 1 diabetes (T1D). In this study, we found a single SH2B3 haplotype significantly associated with increased risk for human T1D, and this haplotype carries the single nucleotide variant rs3184504*T in SH2B3. To better characterize the role of SH2B3 in T1D, we used mouse modeling and found a T cell-intrinsic role for SH2B3 regulating peripheral tolerance. SH2B3 deficiency had minimal effect on TCR signaling or proliferation across antigen doses, yet enhanced cell survival and cytokine signaling including common gamma chain-dependent and interferon-gamma receptor signaling. SH2B3 deficient CD8+T cells showed augmented STAT5-MYC and effector-related gene expression partially reversed with blocking autocrine IL-2 in culture. Using the RIP-mOVA model, we found CD8+ T cells lacking SH2B3 promoted early islet destruction and diabetes without requiring CD4+ T cell help. SH2B3-deficient cells demonstrated increased survival post-transfer compared to control cells despite a similar proliferation profile in the same host. Next, we created a spontaneous NOD .Sh2b3 -/- mouse model and found markedly increased incidence and accelerated T1D across sexes. Collectively, these studies identify SH2B3 as a critical mediator of peripheral T cell tolerance limiting the T cell response to self-antigens. Article Highlights: The rs3184504 polymorphism, encoding a hypomorphic variant of the negative regulator SH2B3, strongly associates with T1D.SH2B3 deficiency results in hypersensitivity to cytokines, including IL-2, in murine CD4+ and CD8+ T cells.SH2B3 deficient CD8+ T cells exhibit a comparable transcriptome to wild-type CD8+ T cells at baseline, but upon antigen stimulation SH2B3 deficient cells upregulate genes characteristic of enhanced JAK/STAT signaling and effector functions.We found a T-cell intrinsic role of SH2B3 leading to severe islet destruction in an adoptive transfer murine T1D model, while global SH2B3 deficiency accelerated spontaneous NOD diabetes across sexes.

16.
Cytokine ; 182: 156718, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39084067

RESUMEN

OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.


Asunto(s)
Citocinas , Citometría de Flujo , Análisis de Semen , Semen , Motilidad Espermática , Humanos , Masculino , Semen/metabolismo , Adulto , Citocinas/sangre , Citocinas/metabolismo , Citometría de Flujo/métodos , Análisis de Semen/métodos , Interleucina-5/metabolismo , Interleucina-5/sangre , Interleucina-17/sangre , Interleucina-17/metabolismo , Interleucina-17/análisis , Recuento de Espermatozoides , Interleucina-6/sangre , Interleucina-6/análisis , Interleucina-6/metabolismo , Interleucina-8/sangre , Interleucina-8/metabolismo , Interleucina-8/análisis , Interleucina-12/sangre , Interleucina-12/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/análisis , Interferón gamma/sangre , Interferón gamma/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/análisis , Interleucina-10/sangre , Interleucina-10/metabolismo , Interleucina-10/análisis , Azoospermia/metabolismo , Azoospermia/sangre , Interleucina-2/sangre , Interleucina-2/metabolismo , Interleucina-2/análisis , Interleucina-4/sangre , Interleucina-4/metabolismo , Interleucina-4/análisis , Oligospermia/metabolismo
17.
Int Immunopharmacol ; 138: 112651, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38986303

RESUMEN

Peripheral blood mononuclear cells (PBMC), sourced autologously, offer numerous advantages when procured: easier acquisition process, no in vitro amplification needed, decreased intervention and overall increased acceptability make PBMC an attractive candidate for cell therapy treatment. However, the exact mechanism by which PBMC treat diseases remains poorly understood. Immune imbalance is the pathological basis of many diseases, with macrophages playing a crucial role in this process. However, research on the role and mechanisms of PBMC in regulating macrophages remains scarce. This study employed an in vitro co-culture model of PBMC and RAW264.7 macrophages to explore the role and mechanisms of PBMC in regulating macrophages. The results showed that the co-culturing led to decreased expression of inflammatory cytokines and increased expression of anti-inflammatory cytokines in RAW264.7 or in the culture supernatant. Additionally, the pro-inflammatory, tissue matrix-degrading M1 macrophages decreased, while the anti-inflammatory, matrix-synthesizing, regenerative M2 macrophages increased in both RAW264.7 and monocytes within PBMC. Moreover, co-cultured macrophages exhibited a significantly decreased p-STAT1/STAT1 ratio, while the p-STAT6/STAT6 ratio significantly increased. This suggests that PBMC may inhibit M1 macrophage polarization by blocking STAT1 signaling cascades and may promote M2 macrophage polarization through the activation of STAT6 signaling cascades. Overall, this study sheds light on the role and mechanism of PBMC in regulating macrophages. Moreover, it was found that monocytes within co-cultured PBMC differentiated into M2 macrophages in the presence of macrophages. This finding provides experimental evidence for the use of PBMC in treating inflammatory diseases, especially macrophage-depleting inflammatory diseases such as osteoarthritis.


Asunto(s)
Técnicas de Cocultivo , Leucocitos Mononucleares , Macrófagos , Factor de Transcripción STAT1 , Factor de Transcripción STAT6 , Transducción de Señal , Animales , Ratones , Citocinas/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Activación de Macrófagos , Macrófagos/inmunología , Macrófagos/metabolismo , Células RAW 264.7 , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT6/metabolismo
18.
Reprod Sci ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026051

RESUMEN

To retrospectively analyze the fertility outcomes and prognosis of gestational trophoblastic disease (GTD) patients, providing a basis for targeted fertility guidance and counseling. 82 GTD patients of childbearing age who received treatment at the Obstetrics and Gynecology Department of Lanzhou University First Hospital from January 2016 to January 2023 were stratified into re-pregnancy (n = 20) and non-re-pregnancy (n = 33) cohorts based on their pregnancy outcomes. The impacts of various factors on pregnancy outcomes were subsequently evaluated, encompassing the rates of subsequent pregnancies, live births, miscarriages, ectopic pregnancies, and ongoing pregnancies. Finally, logistics regression model was employed to analyze the risk factors affecting re-pregnancy in GTD patients. The study delineated those patients with different GTD pathologies had varying re-pregnancy rates (mole, erosive mole and choriocarcinoma accounted for 66.04%, 30.19% and 3.77%, respectively). Treatment predominantly involved uterine curettage, with fewer cases receiving chemotherapy alone or in conjunction with curettage accounted for 67.92%, 5.66%, and 26.42%, respectively. The average chemotherapy frequency was 4.59 ± 2.43 sessions, and a majority sought reproductive counseling. Re-pregnancy occurred in 37.74% of patients. The live birth rate was 65.00%, with miscarriage and ectopic pregnancy rates at 25.00% and 5.00% respectively. Logistic regression analysis pinpointed the absence of pre-pregnancy counseling as a significant independent risk factor for re-pregnancy in GTD patients (p < 0.05). While chemotherapy may influence ovarian function, with the majority of patients desiring children post-recovery, pregnancy rates remain high. Fertility counseling significantly enhances re-pregnancy success rates in GTD survivors, emphasizing its recommendation for those aiming to conceive post-recovery.

19.
Brain Inj ; 38(12): 985-991, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-38845346

RESUMEN

OBJECTIVE: This research aimed to evaluate the impact of grading and zoning nursing management on traumatic brain injury (TBI) patients' emergency treatment outcomes. METHODS: This randomized controlled trial included 200 TBI patients. They were treated with a conventional care (control group, n = 100) and a novel grading and zoning approach (study group, n = 100), respectively. This innovative model organized care into levels based on urgency and complexity, facilitating targeted medical response and resource allocation. Key metrics compared included demographic profiles, consultation efficiency (time metrics and emergency treatment rates), physiological parameters (HR, RR, MAP, SpO2, RBS), and patient outcomes (hospital and ICU stays, complication rates, and emergency outcomes). RESULTS: The study group demonstrated significantly improved consultation efficiency, with reduced times for physician visits, examinations, emergency stays, and specialist referrals (all p < 0.001), alongside a higher emergency treatment rate (93% vs. 79%, p = 0.004), notably better physiological stability, improved HR, RR, MAP, SpO2 and RBS (p < 0.001), shorter hospital and ICU stays, fewer complications, and superior emergency outcomes. CONCLUSION: Grading and zoning nursing management substantially enhances TBI patients' emergency care efficiency and clinical outcomes, suggesting a viable model for improving emergency treatment protocols.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Humanos , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/enfermería , Masculino , Femenino , Adulto , Persona de Mediana Edad , Servicios Médicos de Urgencia , Resultado del Tratamiento , Adulto Joven
20.
Child Dev ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38887788

RESUMEN

The study examined how children's self-regulation skills measured by the strengths and weaknesses of ADHD symptoms and normal behavior rating are associated with story comprehension and how verbal engagement and e-book discussion prompts moderate this relation. Children aged 3-7 (N = 111, 50% female, Chinese as first language) read an interactive Chinese-English bilingual story e-book with or without discussion prompts twice with their parents (2020-2021). Results demonstrated that the lower children's self-regulation skills, the more they struggled with story comprehension. Critically, our data suggest that embedding e-book discussion prompts and more verbalization in English can mitigate this negative association for children with inattention/hyperactivity. These findings have critical implications for future e-book design, interventions, and home reading practice for children with inattention/hyperactivity and those at risk for attention deficit/hyperactivity disorder.

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