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RATIONALE: Tachycardia is a common arrhythmia in clinical practice, and its pathogenesis is mostly related to reentry. However, there are also a few tachycardia that are not related to reentry. Actively clarifying the pathogenesis of these non-reentry related tachycardia is of great significance for its treatment. PATIENT CONCERNS: A 55-year-old female patient presented with recurrent palpitations with a fastest heart rate of 180 beats/minute 10 years ago. DIAGNOSIS: Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT). INTERVENTIONS: DAVNNT can be cured by radiofrequency ablation of atrioventricular nodal slow path modification. OUTCOMES: The tachycardia has stopped. CONCLUSION: DAVNNT is a rare disease in clinical practice. Its characteristic is not reentration-related arrhythmias, but the phenomenon of increased heart rate caused by electrical conduction down the double pathway of atrioventricular nodal tract and subsequent pathway. Electrophysiological examination helps to clarify the diagnosis and pathogenesis, and catheter ablation can cure the disease.

Asunto(s)

Ablación por Catéter , Humanos , Femenino , Persona de Mediana Edad , Ablación por Catéter/métodos , Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Taquicardia por Reentrada en el Nodo Atrioventricular/fisiopatología , Electrocardiografía , Nodo Atrioventricular/fisiopatología , Nodo Atrioventricular/cirugía

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Histidine (His) is a semi-essential amino acid and a unique key neurotransmitter involved in numerous physiological processes. An excessive or deficient amount of His in the body can lead to various related diseases. However, since the chemical structures of L-His and its metabolites (such as histamine (Ha), imidazole-4-acetate (ImA), etc.) are very similar, simple and efficient selective detection of L-His and its related metabolites is of great importance but remains a great challenge. Herein, we successfully designed and synthesized a DMSO-assisted iridium(III) complex (Ir1-DMSO), which can be applied as a "turn-on" photoluminescence (PL) probe for the selective detection and quantification of L-His/Ha. More importantly, Ir1-DMSO exhibited good sensitivity, high selectivity, and anti-interference capability for L-His/Ha/His-containing proteins, which is advantageous due to its simple fabrication and low technical demands. This was attributed to the reaction of Ir1-DMSO with imidazole and amino groups of L-His/Ha. Furthermore, we show the utility of Ir1-DMSO as a PL imaging agent in cultures of E. coli and S. aureus. Considering its diversity of composition and structural flexibility, it can be extended to other solvents and Ir-ligand complexes for various analyses based on specific molecular recognition sensing platforms.

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Cadmium (Cd) is a toxic contaminant widely spread in natural and industrial environments. Adolescent exposure to Cd increases risk for obesity-related morbidity in young adults including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Despite this recognition, the direct impact of adolescent Cd exposure on the progression of MASLD later in life, and the mechanisms underlying these effects, remain unclear. Here, adolescent rats received control diet or diets containing 2 mg Cd2+/kg feed for 4 weeks, and then HFD containing 15% lard or control diet in young adult rats was selected for 6 weeks to clarify this issue. Data firstly showed that HFD-fed rats in young adulthood due to adolescent Cd exposure exhibited more severe MASLD, evidenced by increased liver damage, disordered serum and hepatic lipid levels, and activated NLRP3 inflammasome. Hepatic transcriptome analysis revealed the potential effects of mitochondrial dysfunction in aggravated MASLD due to Cd exposure. Verification data further confirmed that mitochondrial structure and function were targeted and disrupted during this process, shown by broken mitochondrial ridges, decreased mitochondrial membrane potential, imbalanced mitochondrial dynamic, insufficient ATP concentration, and enhanced mitochondrial ROS generation. However, mitophagy is inactively involved in clearance of damaged mitochondria induced by early Cd in HFD condition due to inhibited mitophagy receptor FUNDC1. In contrast, FUNDC1-dependent mitophagy activation prevents lipotoxicity aggravated by early Cd via suppressing mitochondrial ROS generation. Collectively, our data show that insufficient FUNDC1-dependent mitophagy can drive the transition from HFD-induced MASLD to MASH, and accordingly, these findings will provide a better understanding of potential mechanism of diet-induced metabolic diseases in the context of early environmental Cd exposure.

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Acute pancreatitis (AP) is a prevalent gastrointestinal disorder. The immune response plays a crucial role in AP progression. However, the impact of immune regulatory checkpoint PD-L1 on severe acute pancreatitis (SAP) remains uncertain. Hence, this study aimed to examine the influence of PD-L1 on SAP. We assessed PD-L1 expression in neutrophils and monocytes obtained from SAP patients. We induced SAP in C57BL/6J mice, PD-L1 gene-deficient mice, and PD-L1 humanized mice using intraperitoneal injections of cerulein plus lipopolysaccharide. Prior to the initial cerulein injection, a PD-L1 inhibitor was administered. Pancreatic tissues were collected for morphological and immunohistochemical evaluation, and serum levels of amylase, lipase, and cytokines were measured. Flow cytometry analysis was performed using peripheral blood cells. The expression of PD-L1 in neutrophils and monocytes was significantly higher in SAP patients compared to healthy individuals. Likewise, the expression of PD-L1 in inflammatory cells in the peripheral blood of SAP-induced C57BL/6J mice was notably higher than in the control group. In mice with PD-L1 deficiency, SAP model exhibited lower pancreatic pathology scores, amylase, lipase, and cytokine levels compared to wild-type mice. PD-L1 deletion resulted in reduced neutrophil apoptosis, leading to an earlier peak in neutrophil apoptosis. Furthermore, it decreased early monocyte apoptosis and diminished the peak of T lymphocyte apoptosis. Within the SAP model, administration of a PD-L1 inhibitor reduced pancreatic pathology scores, amylase, lipase, and cytokine levels in both C57BL/6J mice and PD-L1 humanized mice. These findings suggest that inhibiting PD-L1 expression can alleviate the severity of SAP.

Asunto(s)

Apoptosis , Antígeno B7-H1 , Monocitos , Neutrófilos , Páncreas , Pancreatitis , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Amilasas/sangre , Apoptosis/efectos de los fármacos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Ceruletida , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Lipasa/sangre , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/inmunología , Monocitos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/efectos de los fármacos , Páncreas/efectos de los fármacos , Páncreas/inmunología , Páncreas/patología , Pancreatitis/inmunología , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Pancreatitis/patología

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Sphingosine-1-phosphate (S1P) is biologically active lipid, leading to neuroinflammation and macrophage invasion in central nervous system, plays an important role in the development of multiple sclerosis (MS) model in experimental allergic encephalomyelitis (EAE) rats. Vitamin D is observed to be a key factor in regulating cell S1P levels. We detected vitamin D can alleviate the symptoms of EAE rats, but the exact mechanism is unclear. In PC12 cells, vitamin D can reverse S1P-induced cell death, but the signaling pathway unclear. This study was aimed to investigate S1P regulation mechanism or signaling pathway mediated by vitamin D in EAE and PC12 model. In our experiments, S1P and Sphingosine kinase type 1 (SphK1) mRNA and protein expression in EAE rats group, control group, vitamin D feeding group were detected by HPLC, ELISA, RT-PCR and western blot. PC12 cell death was detected by Propidium (PI) staining. VDR plasmid overexpression and RNA interference, immunofluorescence, real-time cell analysis, protein immunoblotting was used to detect SphK1 transcriptional regulation, cell-substrate attachment quality, the signaling pathway of cell apoptosis and inflammation related gene expression (Bax/Bcl-2, Casepase-3, Il-6, TGF-ß, TNF-α). Our study showed vitamin D can reverse the elevation of S1P level in EAE rats, reduce the severity and shorten the course of EAE. 1,25-(OH) 2D3 coupled with vitamin D receptor (VDR) inhibited SphK1 transcription. 1,25-(OH)2D3 significantly reduced PC12 cell death rate induced by S1P, in addition improved the cell substrate attachment quality. 1,25-(OH) 2D3 can block S1P-induced p-ERK activation and PI3K /Akt signaling pathway reduced Il-6, TGF-ß, TNF-α cytokine release and Bax/Bcl-2, Casepase-3 apoptosis protein expression. On the other hand, immunofluorescence staining showed 1,25-(OH) 2D3 can increase the expression of neuronal perinuclear protein MAP2 in PC12 cells probably protect nerve cells further. In summary, the ameliorative effect of vitamin D was derived from its ability to reduce S1P levels, provides an idea for vitamin D as a combination therapy for disease.

Asunto(s)

Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Fosfotransferasas (Aceptor de Grupo Alcohol) , Ratas , Animales , Vitamina D/farmacología , Factor de Necrosis Tumoral alfa/genética , Interleucina-6 , Proteína X Asociada a bcl-2 , Vitaminas , Lisofosfolípidos/metabolismo , Esfingosina/metabolismo , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Factor de Crecimiento Transformador beta

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Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Asunto(s)

Masculino , Femenino , Humanos , Persona de Mediana Edad , Adulto , Anciano , Anciano de 80 o más Años , Tumores del Estroma Gastrointestinal/cirugía , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Estudios Retrospectivos , Mutación , Pronóstico , Proteínas Proto-Oncogénicas c-kit/genética

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ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

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Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Tumores del Estroma Gastrointestinal/patología , Estudios Retrospectivos , Relevancia Clínica , Mesilato de Imatinib , Biopsia , Proteínas S100

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Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.

Asunto(s)

Masculino , Femenino , Humanos , Persona de Mediana Edad , Tumores del Estroma Gastrointestinal/cirugía , Estudios Retrospectivos , Antineoplásicos/uso terapéutico , Pronóstico , Mesilato de Imatinib/uso terapéutico , Mutación , Proteínas Proto-Oncogénicas c-kit/genética

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Objective:To study the effect of iodine excess on antioxidant capacity and blood lipid in adult.Methods:A survey was conducted in areas with different iodine nutrition levels in Shandong and Shanxi provinces to collect fasting morning urine and venous blood samples of adults. Urinary iodine, serum levels of superoxide dismutase(SOD), malondialdehyde (MDA), total cholesterol (TCHO), triglyceride (TG), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were determined. According to the median urinary iodine of the population in the investigated village, they were divided into appropriate iodine group (100-299 μg/L) and iodine excess group (≥300 μg/L) . Multiple linear regression was used to analyze the effects of iodine nutrition and other factors on oxidative stress indexes and blood lipids. Partial correlation analysis was used to analyze the relationship between iodine nutrition and oxidative stress indexes and blood lipids.Results:A total of 1 049 subjects were included, including 471 in the appropriate iodine group and 578 in the iodine excess group. The median (quartile) urinary iodine of the appropriate iodine group and the iodine excess group was 228.70 (157.02, 341.49) and 558.73 (298.06, 985.06) μg/L, respectively. The serum SOD level of the appropriate iodine group and the iodine excess group was 12.60 (10.83, 14.10) and 11.29 (9.18, 13.10) U/ml, respectively, and the difference between the groups was statistically significant ( U = 92 697.50, P < 0.001). There were statistically significant differences in serum TG, HDL-C and apoB levels between the appropriate iodine group and the iodine excess group ( U = 108 879.50, 96 613.50, 99 050.50, P < 0.05). The results of multiple linear regression showed that after excluding age, gender and body mass index (BMI), there was a negative correlation between iodine nutrition and serum SOD and HDL-C levels [standard regression coefficient ( β) = - 0.196, - 0.294, P < 0.001]. Partial correlation analysis showed that there was a negative correlation between iodine nutrition and serum SOD and HDL-C levels [correlation coefficient ( r) = - 0.16, - 0.09, P < 0.05]. Conclusion:Excessive iodine intake affects oxidative stress and lipid metabolism in human body.

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Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active compound of Amomum compactum Sol.ex Maton volatile oil and an effective drug for the treat-ment of pneumonia,showed remarkable anti-inflammatory effects on colitis pathogenesis.However,its mechanism of action and direct targets remain unclear.This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate so-dium salt-induced colitis mouse model.The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells.In addition,1,8-cineole targets were revealed by drug affinity responsive target stability,thermal shift assay,cellular thermal shift assay,and heat shock protein 90(HSP90)adenosine triphosphatases(ATPase)activity assays.The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function.Mech-anistically,1,8-cineole directly interacted with HSP90 and decreased its ATPase activity,also inhibited nucleotide-binding and oligomerization domain-,leucine rich repeat-,and pyrin domain-containing 3(NLRP3)binding to HSP90 and suppressor of G-two allele of SKP1(SGT1)and suppressed NLRP3 inflammasome activation in macrophages.These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.

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Irradiation based on accelerator is the main method of radionuclide production. In recent years, with the development of theranostics of nuclear medicine, there is a new demand for the preparation of accelerator radionuclides. In this paper, the nuclides and nuclide pairs of theranostics prepared by accelerators are divided into the three categories: nuclides of theranostics, nuclide pairs of theranostics of same element and different elements. The physical properties and current applications of some nuclides and nuclide pairs are introduced. The problems in the application of accelerator radionuclides preparation in China are analyzed, and the application prospect of the integration of accelerator radionuclides diagnosis and treatment is prospected.

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Objective: To investigate the natural history and risk factors for continued allergy in infants with IgE-mediated cow's milk protein allergy (CMPA). Methods: This was a prospective cohort study that included 72 infants under 24 months of age diagnosed with IgE-mediated CMPA in the allergy clinic of the Children's Hospital, Capital Institute of Pediatrics from October 2019 to November 2020. General information, clinical manifestations, serum total IgE, cow's milk specific IgE, and cow's milk protein component specific IgE were collected. Follow-ups were conducted at 24 and 36 months of age, and the patients were divided into the persistent allergy group and the tolerance group based on whether they developed cow's milk tolerance at 36 months of age. Mann-Whitney U test, chi-square test, and binary Logistic regression were used for intergroup comparison and multivariate analysis. Results: Among the 72 CMPA children, there were 42 boys and 30 girls, with an age of 10 (7, 15) months at enrollment. Cow's milk protein tolerance was observed in 32 cases (44%) and 46 cases (64%) at 24 and 36 months of age, respectively. There were 26 cases in the persistent allergy group and 46 cases in the tolerance group. The proportion of respiratory symptoms, history of wheezing, positive specific IgE for α-lactalbumin and the total IgE level in the persistent allergy group were higher than that in the tolerance group (7 cases (27%) vs. 0, 6 cases (23%) vs. 2 cases (4%), 67% (14/21) vs. 26% (10/39), 225 (151, 616) vs. 48 (21, 185) kU/L, χ2=10.82, 4.16, 9.57, Z=4.07, all P<0.05). Multivariate Logistic regression analysis showed that anaphylaxis (OR=21.14, 95%CI 2.55-175.14, P=0.005), a history of allergic rhinitis (OR=5.94, 95%CI 1.54-22.86, P=0.005), elevated milk specific IgE (OR=1.04, 95%CI 1.01-1.08, P=0.024), and positive casein specific IgE (OR=6.64, 95%CI 1.39-31.69, P=0.018) were risk factors for continuous CMPA. Conclusions: Most infants with IgE-mediated CMPA can achieve tolerance within 3 years. Anaphylaxis, a history of allergic rhinitis, elevated milk specific IgE levels, and casein sensitization are risk factors for continuous allergy.

Asunto(s)

Masculino , Animales , Femenino , Bovinos , Lactante , Humanos , Niño , Hipersensibilidad a la Leche/diagnóstico , Caseínas , Estudios Prospectivos , Anafilaxia , Factores de Riesgo , Rinitis Alérgica , Inmunoglobulina E , Proteínas de la Leche/efectos adversos

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In the present study, the polyimmunoglobulin receptor-like (pIgRL) of large yellow croaker (Larimichthys crocea) was first cloned and characterized. LcpIgRL's full-length cDNA was 1610 bp, encoding 377 amino acids, and the protein's predicted molecular weight was 41.9 kDa, containing two immunoglobulin-like structural domains. The transcript levels of LcpIgRL in different tissues of healthy large yellow croaker were examined by real-time fluorescence quantitative PCR, and the results showed that the gills and head kidney had the highest levels. Within 36 h of the large yellow croaker being infected with Vibrio harveyi, pIgRL mRNA first increased and then decreased in all determined tissues, with the highest expression in the skin and hindgut. Furthermore, a recombinant protein of the extracellular region of LcpIgRL was expressed in E. coli BL21, and a murine rLcpIgRL polyclonal antibody was prepared, which could react specifically with the natural LcpIgRL in skin mucus, but no natural LcpIgRL was detected in serum. Meanwhile, it was found that the rLcpIgRL could bind to the recombinant IgM and the natural IgM, indicating that LcpIgRL could mediate the transport of IgM in mucus. In addition, rLcpIgRL binds to Aeromonas hydrophila and V. harveyi, as well as lipopolysaccharide (LPS) and various saccharides, and reduced binding to bacteria was observed under LPS treatment, suggesting that LcpIgRL can bind to bacteria to prevent infection and that saccharide binding is an important mechanism of interaction between pIgRL and bacteria.

Asunto(s)

Perciformes , Receptores de Inmunoglobulina Polimérica , Animales , Ratones , Receptores de Inmunoglobulina Polimérica/genética , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Escherichia coli/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Inmunoglobulina M/genética , Proteínas de Peces/química , Filogenia

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Background: With uncontrolled inflammatory progression, acute pancreatitis (AP) can progress to severe acute pancreatitis (SAP). Inflammation and parenchymal cell death are key pathologic responses of AP. Toll-like receptor 4 (TLR4) plays a pro-inflammatory role in AP. Myeloid differentiation primary response protein 88 (MyD88) is the most essential utilized adaptor of TLR4, but its role in AP remains unclear. We investigated the potential role of MyD88 in the pathogenesis of AP. Methods: An AP model was induced by administering either cerulein or L-arginine to wild-type or MyD88-deficient mice. Additionally, receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 (Nec-1) was administered to the MyD88-/- mice. The severity of AP was determined by measuring serum amylase and lipase activities, quantifying pancreatic myeloperoxidase (MPO) activity, and histological examination. The effects of MyD88 deletion on cell death and the inflammatory response were determined by measuring apoptosis, necrosis, and inflammatory cytokines. Western blot was used to assess the necrotic mediators, RIP1 and RIP3. Results: The deletion of MyD88 resulted in more severe acute experimental pancreatitis as assessed by increased amylase and lipase activities, increased pancreatic MPO activity, a reduced anti-inflammatory response, reduced apoptosis, and increased necrosis. Additionally, Nec-1 treatment significantly reduced necrosis in the MyD88-/- mice. Conclusions: The deletion of MyD88 inhibited the TLR4/MyD88-dependent pathway mediated protective immune defense response and enhanced TLR4/MyD88-independent TRIF pathway-mediated pancreatic necrosis, which in turn aggravated the severity of AP. The critical role of MyD88 in immune defense response and cell death indicates that MyD88 represents a potential therapeutic target in the management of AP.

Asunto(s)

Músculos de la Espalda , Pancreatitis Aguda Necrotizante , Absceso , Enfermedad Aguda , Drenaje/efectos adversos , Humanos , Pancreatitis Aguda Necrotizante/complicaciones , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/cirugía , Tomografía Computarizada por Rayos X

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OBJECTIVES: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. METHODS: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. RESULTS: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. CONCLUSIONS: The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

Asunto(s)

Sepsis Neonatal , Sepsis , Ácido Ascórbico , Cisteína , Humanos , Recién Nacido , Metabolómica , Metionina , Piruvatos

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BACKGROUND: The severity of acute pancreatitis in pregnancy (APIP) is correlated with higher risks of maternal and fetal death. AIM: To develop a nomogram that could predict moderately severe and severe acute pancreatitis in pregnancy (MSIP). METHODS: Patients with APIP admitted to West China Hospital between January 2012 and December 2018 were included in this study. They were divided into mild acute pancreatitis in pregnancy (MAIP) and MSIP. Characteristic parameters and laboratory results were collected. The training set and test set were randomly divided at a ratio of 7:3. Least absolute shrinkage and selection operator regression was used to select potential prognostic factors. A nomogram was developed by logistic regression. A random forest model was used to validate the stability of the prediction factors. Receiver operating characteristic curves and calibration curves were used to evaluate the model's predictive performance. RESULTS: A total of 190 patients were included in this study. A total of 134 patients (70.5%) and 56 patients (29.5%) were classified as having MAIP and MSIP, respectively. Four independent predictors (lactate dehydrogenase, triglyceride, cholesterol, and albumin levels) were identified for MSIP. A nomogram prediction model based on these factors was established. The model had areas under the curve of 0.865 and 0.853 in the training and validation sets, respectively. The calibration curves showed that the nomogram has a good consistency. CONCLUSION: A nomogram including lactate dehydrogenase, triglyceride, cholesterol, and albumin levels as independent predictors was built with good performance for MSIP prediction.

Asunto(s)

Pancreatitis , Enfermedad Aguda , Albúminas , Colesterol , Femenino , Humanos , L-Lactato Deshidrogenasa , Nomogramas , Pancreatitis/diagnóstico , Embarazo , Triglicéridos

RESUMEN

BACKGROUND: Spine-hip discordance (SHD) increases fracture risk. However, its prevalence and clinical implications have not been investigated in patients with hip fractures. This study determined the prevalence and association of SHD with mortality and investigated the cause of SHD in patients with hip fractures. METHODS: This study included patients admitted for fragility hip fractures between 2011 and 2020. All patients underwent dual energy X-ray absorptiometry and anteroposterior and lateral views of the lumbosacral spine during admission. Data on demographics, diagnosis, American Society of Anesthesiologists score, and mortality were collected. A T-score difference of more than 1.5 between L1-4 and the femur neck was considered discordant, and 3 groups (lumbar low [LL] discordance, no discordance [ND], and femur neck low [FL] discordance) were compared. In the discordance group, lumbar radiographs were reviewed to determine the cause of discordance. RESULTS: Among 1,220 eligible patients, 130 were excluded due to patient refusal or bilateral hip implantation; therefore, this study included 1,090 patients (271 male and 819 female). The prevalence of LL, ND, and FL was 4.4%, 66.4% and 29.2% in men and 3.9%, 76.1%, and 20.0% women. Mortality was not associated with discordance. The most common causes of discordance were physiological in the LL group and pathological in the FL group for both sexes. CONCLUSIONS: Patients with hip fractures showed lower rates of ND and higher rates of FL compared to the general population. True discordance should be carefully judged for pathological and artifact reasons. The clinical implications of SHD require further investigation.

RESUMEN

Objective:To observe the ratio of helper T cells 17 (Th17)/regulatory T cells (Treg) in peripheral blood of patients with Hashimoto's thyroiditis (HT) and the expression changes of related cytokines in serum, and to explore their role in the occurrence and development of HT.Methods:Using the case-control study method, 35 HT patients examined in the General Hospital of Heilongjiang Beidahuang Group from February to November 2019 were selected as HT group, and 39 healthy people in the same period were selected as control group. Early morning fasting venous blood samples of the two groups were collected to test the levels of thyroid stimulating hormone (TSH), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). The expressions of serum interleukin (IL)-6, IL-17 and transforming growth factor β (TGF-β) were tested by enzyme-linked immunosorbent assay (ELISA); the number of Th17, Treg in peripheral blood were determined by flow cytometry. Results:The levels of TPOAb, TgAb and TSH in HT group [130.60 (43.37, 714.40), 368.10 (136.90, 1 103.00) U/ml, 9.05 (6.62, 15.23) μU/ml] were significantly higher than those in control group [2.66 (1.52, 4.69), 12.63 (11.43, 14.60) U/ml, 1.87 (1.36, 2.23) μU/ml, U = 6.87, 6.62, 4.85, P < 0.001], and the FT 4 level [0.76 (0.63, 1.04) ng/dl] was lower than that in control group [1.14 (1.02, 1.26) ng/dl, U = 7.39, P < 0.001]. The expressions of IL-6, IL-17 and TGF-β in HT group were higher than those in control group ( t = 2.41, 9.04, 2.44, P < 0.05). The number of Th17 and the ratio of Th17/Treg in HT group were higher than those in control group ( t = 4.20, 3.50, P < 0.05), and the number of Treg was lower than that in control group ( t = 4.45, P = 0.001). Conclusion:In HT patients, Th17 are increased, Treg decreased, Th17/Treg ratio increased, and the expressions of IL-6, IL-17 and TGF-β are increased.